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1.
Correction for ‘Highly selective acid-catalyzed olefin isomerization of limonene to terpinolene by kinetic suppression of overreactions in a confined space of porous metal–macrocycle frameworks’ by Wei He et al., Chem. Sci., 2022, 13, 8752–8758, https://doi.org/10.1039/d2sc01561g.The authors regret that there were errors in Fig. 2, Fig. 5 and Fig. 6 in the original article and Fig. S18 of the ESI. The stereochemistry of the chemical structural formulas for (−)-α-pinene (6) and (−)-β-pinene (7) was incorrectly reversed. The correct versions of the figures are shown below, and in the updated version of the ESI.Open in a separate windowFig. 2Metal–macrocycle framework (MMF). (a) Self-assembly of asymmetrically twisted PdII-macrocycles into (b) a porous crystal MMF (sticks model) with five enantiomeric pairs of binding pockets (surface model). (c) Previously reported site-selective adsorption of (−)-α-pinene (6) (space-filling model) on the channel surface of the MMF.1 Blue, yellow, red, or black dashed circles indicate the ceiling-, side-, bottom-, or tubular-pockets of the MMF, respectively. MMF: Pd, yellow; Cl, green; N, blue; C, grey. 6: C, pink; H, white. Hydrogen atoms attached to the MMF were omitted for clarity. Green or blue surface represents exposed Cl or N–H groups of the MMF, respectively.Open in a separate windowFig. 5Investigation of the inhibitory effects of additives on the isomerization reaction of 2 using 2-NBSA@MMF at 25 °C for 102 h.Open in a separate windowFig. 6Crystallographic study of MMFs soaked in (a) a CHCl3 solution containing 1 (1.0 M), (b) a CHCl3 solution containing 2 (1.0 M), and (c) a CH3CN solution containing 7 (1.0 M). MMF: stick model or surface model; 1 and 7: space-filling model; water and CHCl3: stick model. Red dashed circles indicate the bottom pocket of the MMF. MMF: Pd, yellow; Cl, green; N, blue; C, grey. 1: C, yellow; H, white. 7: C, pink; H, white. Water and CHCl3: O, red; H, white; C, grey; Cl, green. Hydrogen atoms attached to the MMF were omitted for clarity. Green and blue surface represents exposed Cl and N–H groups of the MMF, respectively.The Royal Society of Chemistry apologises for these errors and any consequent inconvenience to authors and readers. 相似文献
2.
Correction for ‘Hydrogen-activation mechanism of [Fe] hydrogenase revealed by multi-scale modeling’ by Arndt Robert Finkelmann et al., Chem. Sci., 2014, 5, 4474–4482, DOI: 10.1039/C4SC01605J.The authors regret that there were minor typographical errors in two figures. In Fig. 9 and and11,11, the internuclear distances were swapped. The Fe-bound hydrogen atoms are affected, where Hp is the hydrogen atom proximal to the oxypyridine ligand and Hd is the hydrogen atom distal to the oxypyridine ligand. In Fig. 9, left panel, the distance between Hp and the oxypyridine O atom was given as 1.82 Å and the distance between Hp and the Fe atom was given as 1.7 Å. However, it should read 1.82 Å between Hp and Fe and 1.70 Å between Hp and the oxypyridine O atom. In Fig. 11, top left panel, the distance between Hp and Fe was shown to be 1.70 Å and the distance between Hd and Fe was given as 1.73 Å. However, it should read 1.73 Å between Hp and Fe and 1.70 Å between Hd and Fe. The correct versions of these figures are given below. The results and conclusions are not affected by these typographical errors.Open in a separate windowFig. 9QM/MM-optimized reactant (left) and product (right) structures of the H2 cleavage reaction for the scenario with oxypyridine ligand. Distances are given in Å.Open in a separate windowFig. 11Top row: structures of the H2 adduct for the second scenario with neutral pyridinol; the pyridinol OH can be oriented away from Fe (top left) or towards Fe (top right). Bottom row: products of H2 cleavage, with the proton transferred to the thiolate; with the hydroxyl oriented away from Fe (bottom left) and towards Fe (bottom right). Distances are given in Å; relative energies with respect to the favoured adduct are indicated in red in kcal mol−1.The Royal Society of Chemistry apologises for these errors and any consequent inconvenience to authors and readers. 相似文献
3.
Shuake Kuermanbayi Yaowei Yang Yuxiang Zhao Yabei Li Le Wang Jin Yang Yan Zhou Feng Xu Fei Li 《Chemical science》2022,13(37):11266
Correction for ‘In situ monitoring of functional activity of extracellular matrix stiffness-dependent multidrug resistance protein 1 using scanning electrochemical microscopy’ by Shuake Kuermanbayi et al., Chem. Sci., 2022, https://doi.org/10.1039/d2sc02708a.The authors regret that an incorrect version of Fig. 5f was included in the original article. This error does not affect the conclusions of the original article as the correct Fig. 5f also proves that there is no significant difference in the mRNA levels of MRP1 in the MCF-7 cells on the PA gels with three stiffness. The correct version of Fig. 5 is presented below.Open in a separate windowFig. 1(a and b) Immunofluorescence images and (c and d) the normalized total MRP1 intensities of (a and c) MCF cells and (b and d) MDA-MB-231 cells on the PA gels with stiffness of 2.5, 17.1 and 26.2 kPa, respectively (scale bar: 40 μm). (e) Western blot analysis of the MRP1 expressions of the MCF-7 and MDA-MB-231 cells on the PA gels with stiffness of 2.5, 17.1 and 26.2 kPa, respectively. (f and g) The relative MRP1 mRNA expressions in (f) the MCF-7 cells and (g) the MDA-MB-231 cells on the PA gels with stiffness of 2.5, 17.1 and 26.2 kPa, respectively.The Royal Society of Chemistry apologises for these errors and any consequent inconvenience to authors and readers. 相似文献
4.
Elisabetta Alberico Thomas Leischner Henrik Junge Anja Kammer Rui Sang Jenny Seifert Wolfgang Baumann Anke Spannenberg Kathrin Junge Matthias Beller 《Chemical science》2021,12(47):15772
Correction for ‘HCOOH disproportionation to MeOH promoted by molybdenum PNP complexes’ by Elisabetta Alberico et al., Chem. Sci., 2021, 12, 13101–13119, DOI: 10.1039/D1SC04181A.The authors regret that in Scheme 2 of the original article, complexes 7 and 8 were drawn incorrectly. The solid-state structure of both complexes, as established by X-ray analysis, had been previously reported (7 (ref. 1) and 8 (ref. 2)). In both complexes, the PNP ligand adopts a facial tridentate coordination to molybdenum and not a meridional one, as erroneously shown in Scheme 2 of the original article. The correct ligand arrangements in the metal coordination sphere for complexes 7 and 8 are reported below in Scheme 1.Open in a separate windowScheme 1Mo–PNP complexes tested in the dehydrogenation of HCOOH.Open in a separate windowScheme 2Proposed mechanisms for HCOOH dehydrogenation (red), disproportionation (blue) and decarbonylation (green) promoted by 5. Evidence for the formation of a Mo(iv) species is based on the detection by NMR of H2 and HD following addition of DCOOD to Mo(H)n species (see Fig. SI-31).Please note that complex 8 is also shown in Scheme 4 in the proposed mechanism for HCOOH decarbonylation (green part), and in Fig. 2. In both cases, the correct structure for complex 8 is reported below in Scheme 2 and Fig. 1.Open in a separate windowFig. 1 1H and 31P{1H} NMR spectra of a toluene-d8 solution of {Mo(CH3CN)(CO)2(HN[(CH2CH2P)(CH(CH3)2)2]2} 4 in the presence of 100 equivalents of HCOOH ([Mo] 10−2 M, [HCOOH] 1 M), before (a) and after heating at 90 °C for 1 hour (b). Spectra were recorded at room temperature. Signals related to complex 5 are marked by red dots.Open in a separate windowFig. 2Molecular structure of {Mo(CO)2(CH3CN)[CH3N(CH2CH2P(CH(CH3)2)2)2]} 9. Displacement ellipsoids correspond to 30% probability. Hydrogen atoms are omitted for clarity.Furthermore, a mistake was made in the caption of Fig. 6, showing the solid-state structure of complex 9: the latter has been incorrectly described as a Mo(i)-hydride species {Mo(H)(CO)2(CH3CN)[CH3N(CH2CH2P(CH(CH3)2)2)2]}. The correct formula, in agreement with the X-ray structure, is as follows and is shown above in Fig. 2: {Mo(CO)2(CH3CN)[CH3N(CH2CH2P(CH(CH3)2)2)2]}.The Royal Society of Chemistry apologises for these errors and any consequent inconvenience to authors and readers. 相似文献
5.
Hao Chen Tian-Ren Li Naomi Sakai Celine Besnard Laure Gune Marion Pupier Jasmine Viger-Gravel Konrad Tiefenbacher Stefan Matile 《Chemical science》2022,13(35):10273
Simple enough to be understood and complex enough to be revealing, cascade cyclizations of diepoxides are introduced as new tools to characterize supramolecular catalysis. Decoded product fingerprints are provided for a consistent set of substrate stereoisomers, and shown to report on chemo-, diastereo- and enantioselectivity, mechanism and even autocatalysis. Application of the new tool to representative supramolecular systems reveals, for instance, that pnictogen-bonding catalysis is not only best in breaking the Baldwin rules but also converts substrate diastereomers into completely different products. Within supramolecular capsules, new cyclic hemiacetals from House–Meinwald rearrangements are identified, and autocatalysis on anion–π catalysts is found to be independent of substrate stereochemistry. Decoded product fingerprints further support that the involved epoxide-opening polyether cascade cyclizations are directional, racemization-free, and interconnected, at least partially. The discovery of unique characteristics for all catalysts tested would not have been possible without decoded cascade cyclization fingerprints, thus validating the existence and significance of privileged platforms to elucidate supramolecular catalysis. Once decoded, cascade cyclization fingerprints are easily and broadly applicable, ready for use in the community.Hyperresponsive XL product space identifies polyether cascade fingerprinting as an attractive tool to elucidate supramolecular catalysis, including pnictogen-bonding, capsule and anion–π catalysts.One general expectation from supramolecular catalysis1–10 is that new ways to interact will provide new ways to transform on the molecular level. This translates to access to new reactivity and products, at best contributing to new solutions for otherwise persistent challenges in science and society. While these high expectations are attracting attention to the development of supramolecular catalysts, their systematic characterization is much less advanced. Most classical and modern benchmark reactions1,9 are limited to one mechanism and cover little product space, also concerning chemo- and stereochemistry. To maximize the comparability of supramolecular catalysts, the ideal reaction would respond to as many parameters as possible at still manageable complexity. Epoxide opening polyether cascade cyclizations10–13 promise to meet these requirements for a privileged platform to evaluate supramolecular catalysts. Charismatic in chemistry and biology, they have attracted the attention of many giants in the field.11 They afford the largest polycyclic natural products, regularly featuring more than 10 rings made in one cascade. While product diversity of longer cascades is too complex and single cyclizations are too simple, minimalist cascades from diepoxide substrates such as 1 cover large structural space at tractable complexity (Fig. 1). In substrate 1, supramolecular catalysts can activate nucleophile, electrophile and leaving group, and stabilize cationic and anionic transition states and reactive intermediates (Fig. 1a). Cyclizations can follow either the 5-exo-tet selectivity predicted by the Baldwin rules (B) or anti-Baldwin (A) 6-endo-tet selectivity, leading to the four constitutional isomers 2–5 (Fig. 1a and and2).2). They can occur with normal or reverse directionally,12 forming ring 1 or ring 2 first, respectively (Fig. 1b). They can operate with pseudo SN2, SN1, or mixed mechanisms, and can integrate contributions from autocatalysis.10,13 The stereochemistry covers cis–trans isomers at epoxide 1 and syn–anti isomers with regard to the two epoxides (Fig. 1c). This translates to the stereochemistry of products such as 2–5 at the ring junction and the exocyclic substituents of ring 2. Besides this expected diversity, the product space of the privileged substrate 1 further expands into structures that remain to be discovered, as demonstrated with two new products reported in this study.Open in a separate windowFig. 1(a) Epoxide-opening ether cascade cyclizations from diepoxide 1 as privileged platform to elaborate on supramolecular catalysis, with indication of possible contributions from electron-donating (red) and electron-accepting catalyst motifs (blue), exo-tet Baldwin (B) or endo-tet anti-Baldwin (A) chemoselectivity, (b) normal and reverse directionality, and (c) stereochemistry in selected substrates and products.Open in a separate windowFig. 2(a) Decoded product fingerprints for selected catalysts: Color-coded pie charts for products 2 (red), 3 (yellow), 4 (green), 5 (blue), 6 and 7 (teal) obtained from stereoisomers of cis and trans substrate isomers 1 with representative supramolecular catalysts 8–10 compared to general Brønsted acid (AcOH); results for cis,anti and trans,syn isomers of 1 are calculated (from data for the other diastereomer and the mixture of diastereomers in the respective series); estimated errors ± 5%. (b) Experimental results for cis,anti-1 cyclized with catalyst 9. (c) Selected X-ray structures from the BA series (p-bromobenzoyl derivatives). (d) Structure of catalysts, with indication of selected π-basic surfaces and hydrogen-bond donors on capsule 8 assembled from monomers 11, the cyclopean σ hole of pnictogen-bonding catalyst 9, and the π-acidic surface on anion–π catalyst 10.So far, substrate 1 has been used as a mixture of stereoisomers to characterize supramolecular catalysts.13 While results were intriguing, they could not be rationalized. Overlap of different trends obscured the key information and made product fingerprints dependent on the composition of the substrate mixtures. However, the observed hyperresponsiveness of the large product space suggested that decoded product fingerprints could provide a general tool to elucidate supramolecular catalysis.To assess the possibly privileged nature of diepoxide 1 as unifying substrate for supramolecular catalysis, we decided to synthesize and evaluate the necessary stereoisomers separately. The stereoisomers cis-1 and trans-1 were prepared by oxidation of the respective silyl protected cis- and trans-olefins with m-CPBA (meta-chloroperoxybenzoic acid), followed by deprotection (Fig. 2, Schemes S1 and S2†). They were obtained as roughly equimolar mixtures of syn- and anti-diastereomers (cis-1: dr 54 : 46, trans-1: dr 50 : 50). Shi epoxidation14 in place of m-CPBA afforded enantioenriched cis,syn-1 (dr 89 : 11; dr 20 : 1 after purification) and trans,anti-1 (dr 82 : 18; dr 20 : 1 after purification) accordingly with unknown absolute configuration. These four substrates were sufficient to realize the complete analysis of the system because the product fingerprints for the remaining diastereomers cis,anti-1 and trans,syn-1 could be obtained from the difference of cis,syn-1 and trans,anti-1 and the respective mixture of diastereomers cis-1 and trans-1 (Fig. 2).To decode product fingerprints from different catalysts in their respective color-coded pie charts, all individual products were isolated and the diagnostic regions of their 1H NMR spectra and chiral GC traces were assembled for direct comparison (Fig. 3). In most GC traces, the two peaks were well resolved for each pair of enantiomers, confirming access to nearly all stereochemical information. The resulting unified fingerprint of the complete system then allowed to rapidly assign products obtained from different catalysts down to the level of enantiomers. The validity of most structures was confirmed by X-ray crystallography (Fig. 2c and S78–S83†). If necessary, derivatives were prepared to facilitate the growth of single crystals.Open in a separate windowFig. 3Decoded product fingerprints: Diagnostic regions of 1H NMR spectra (a and b) and chiral GC (c and d) of purified cascade cyclization products from cis (a and c) and trans (b and d) substrate isomers 1 above representative examples of mixtures produced by AcOH and 9 combined (a and c), and by 8 (b and d).With the analytics in place, product fingerprints were recorded for representative supramolecular catalysts 8–10 in comparison to general Brønsted acid catalysis (Fig. 2). In the cis series, the product mixtures obtained from different catalysts contained all four constitutional isomers expected from Baldwin and anti-Baldwin cyclizations, that is cis-(BB)-2, cis-(BA)-3, cis-(AB)-4 and cis-(AA)-5 (Fig. 2a and and3a).3a). In contrast, trans-(AB)-4 was absent in the trans series, and two new products 6 and 7 were found instead (vide infra, Fig. 2a and and3b3b).In both the cis and the trans series, general Brønsted acid catalysis with AcOH was confirmed to follow the Baldwin rules almost exclusively, affording mostly (BB)-2 (Fig. 2). In the cis series, the supramolecular capsules 8 violated the Baldwin rules significantly (Fig. 2a). Capsules 8 self-assemble from resorcinarenes 11 and water (Fig. 2d).3,4 Their internal surface offers hydrogen-bond donors and π-basic aromatic planes for catalysis within their confined interior.3,4 Unique selectivities have been reported, also for bioinspired terpene cyclizations, for instance.4 From cascade cyclization with the mixture of cis-1 diastereomers in capsules 8, cis-(BA)-3 was obtained as the main product besides the still preferred cis-(BB)-2 (Fig. 2a). The pure cis,syn-1 showed a clearly different product distribution, characterized by an increased power to violate the Baldwin rule in cycle 2, affording cis-(BA)-3 as the main product. The calculated fingerprint for the products of cis,anti-1 gave the complementary dominance of the Baldwin conformant cis-(BB)-2 instead.Differences in selectivity for the syn- and anti-diastereomers in the cis series were most spectacular with the pnictogen-bonding catalyst 9 (Fig. 2a). Pnictogen-bonding catalysis has been introduced recently5–7 for consideration as the non-covalent counterpart of Lewis acid catalysis, analogous to hydrogen-bonding catalysis as non-covalent counterpart of Brønsted acid catalysis.7 Catalyst 9 is centered around an antimony V with one deep σ hole acting as pnictogen-bond donor to initiate catalysis.7 Catalyst 9 has been shown previously to efficiently break the Baldwin rules in polyether cyclizations.7,13 In the newly devised pie chart fingerprint, orthodox cis-(BB)-2 was indeed essentially absent (Fig. 2a). The mixture of diastereomers cis-1 afforded cis-(BA)-3 and cis-(AB)-4 as main products. In sharp contrast, diastereo-pure cis,syn-1 gave mostly cis,syn-(BA)-3. As a consequence, the calculated product fingerprint of cis,anti-1 showed the highly selective formation of cis,anti-(AB)-4.Selective access to cis,anti-(AB)-4 with pnictogen-bonding catalyst 9 was remarkable because none of the other stereoisomers of (AB)-4 were observed throughout the study (Fig. 3a and and4a).4a). Exclusive access to cis,anti-(AB)-4 from cis,anti-1 was understandable considering cascade cyclization with normal directionality (Fig. 1). Namely, the endo-tet cyclization of ring 1 will afford the reactive intermediate III (Fig. 4b). From this intermediate III, the exo-tet Baldwin conformant formation of ring 2 is possibly supported by an intramolecular hydrogen bond (Fig. 4b and c, arrows), which activates the nucleophile and places an epoxide in an equatorial position.Open in a separate windowFig. 4(a) The formation of only one out of four possible (AB) isomers 4 and (b) the origin of the selectivity and products found in the anti-Baldwin series with capsule 8 and pnictogen-bonding catalyst 9, with (c) selected X-ray structures.These favorable conditions to access cis,anti-(AB)-4 from cis,anti-1 contrasted sharply with the situation with all other diastereomers. In the cis series, access to the complementary cis,syn-(AB)-4 from cis,syn-1 is disfavored although the nucleophile in the reactive intermediate IV remains possibly activated by intramolecular hydrogen bonding. However, the axial orientations of epoxide in intermediate IV and a very bulky tertiary alcohol in product 4 make this reaction unlikely.With cis,syn-(AB)-4 from cis,syn-1 unfavorable, reactive intermediate IV obtained from an anti-Baldwin cyclization of ring 1 needs an alternative solution. An obvious choice is continuation with another endo-tet anti-Baldwin cyclization for ring 2 to result in cis,syn-(AA)-5 with a more flexible cis-fused oxepane ring. This cis,syn-(AA)-5 was indeed part of the product fingerprint of cis,syn-1 cyclized with pnictogen-bonding catalyst 9 (Fig. 2a). The markedly different amounts of cis,syn-(AA)-5 and cis,anti-(AB)-4 obtained from cis,syn-1 and cis,anti-1, respectively (Fig. 2a), would then suggest that normal cascade cyclizations are interconnected, possibly concerted (Fig. 1b).The differences of the selectivity of the cascade cyclization of cis,syn-1 and cis,anti-1 with pnictogen-bonding catalyst 9 (Fig. 2a) and the importance of the implications called for the experimental validation of the calculated results for cis,anti-1. Therefore, pure diastereomer cis,anti-1 was prepared and cyclized using catalyst 9. The experimental product fingerprint was very similar to the calculated one, confirming the unique cis,anti-(AB)-4 as the main product of the reaction (Fig. 2b). This results also validated the use of calculated data to decode complex product fingerprints completely.In the trans series, pnictogen-bonding catalyst 9 again broke the Baldwin rules most efficiently (Fig. 2a). For all diastereomers, trans-(AA)-5 was observed as the main product with more than 75% yield. This exceptional selectivity was understandable considering the reactive intermediates V and VI after the endo-tet cyclization of ring 1 (Fig. 4b). Contrary to intermediates III and IV in the cis series, the methyl substituent at the ring junction is in axial position also with regard to ring 2. 1,3-Diaxial interactions of the approaching electrophile with this methyl thus hinder the formation of this ring 2 by an exo-tet cyclization. Presumably for this reason, the trans-fused bis-oxane products trans,anti-(AB)-4 and trans,syn-(AB)-4 were not observed. With Baldwin cyclizations hindered, endo-tet anti-Baldwin cyclizations occurred instead to afford the respective trans,anti-(AA)-5 and trans,syn-(AA)-5 with very high selectivity (Fig. 2a).The supramolecular capsules 8 applied to the trans series yielded two new products 6 and 7 (Fig. 2). Product 6 was identified by 2D NMR spectroscopy to be a hemiacetal cyclized on an anti-Baldwin ring 1 (Fig. S72†). It exists in equilibrium with the open ketone form 12, which results in dynamic epimerization at the “anomeric center” (Fig. 2 and and4).4). Derivatization of hemiacetal 6 with aromatic hydrazines gave the respective hydrazones (Fig. S76 and S77†). Product 7 was identified as an acyclic allyl alcohol extending from an anti-Baldwin ring 1 (Fig. 2 and S73–S75†). Both new products might originate from intermediate VII, which is generated from substrate 1 by endo-tet cyclization of ring 1 and the opening of epoxide 2 to afford the tertiary carbocation (Fig. 4b). From intermediate VII, the formation of allyl alcohol 7 only requires a proton abstraction from one of the two adjacent methyl groups. Ketone 12 originates from the same intermediate VIIvia House-Meinwald rearrangement,15 that is a 1,2-hydride shift. Similar processes might occur with trans-diepoxide 1 to give an alternative cationic intermediate VIII, which can proceed through reverse cyclization (Fig. 1b) to give products 6 and 7. Stabilization of carbocations via cation–π interactions is a distinct feature of this type of capsules.3,4The formation of these two new products in capsule 8 could be understood considering the inaccessibility of both AB products in the trans series, i.e., trans,syn-(AB)-4 and trans,anti-(AB)-4, with the explored catalysts (Fig. 4a). As already mentioned, the anti-Baldwin cyclization from trans,anti-1 and trans,syn-1 into intermediates V and VI with ring 1 is unproblematic, whereas continuation with exo-tet Baldwin cyclization of ring 2 is hindered by an axial methyl and, compared to the cis series, missing intramolecular activation of the nucleophile (Fig. 4b). With pnictogen-bonding catalyst 9, the solution was an alternative endo-tet anti-Baldwin cyclization into the trans-fused AA products 5, as discussed above (Fig. 2a and and4b).4b). In capsule 8, this endo-tet anti-Baldwin continuation of the cascade was not favorable. The reason for this distinctive selectivity within capsule 8 remains to be explored. In contrast to the other catalysts, the capsule may be able to stabilize cation VII better due to cation–π stabilization, making this pathway accessible.While the new oxanes 6 and 7 were obtained as main products from trans,anti-1 and trans,syn-1 with similar yields, the composition of the side products differed in the respective fingerprints (Fig. 2a). Cyclization of trans,syn-1 gave trans-(BB)-2 as the main side product, while trans,anti-1 gave trans,anti-(AA)-5 as the main side product. This difference was of interest because it could support that the cascade cyclizations might be interconnected, possibly concerted, at least in the present context.While capsules 8 excelled with access to new products in the trans series and pnictogen-bonding catalysts 9 with unique AB-BA selectivity on the level of diastereomers in the cis series, anion–π catalysts gave mostly Baldwin products like general Brønsted acid catalysis, independent of the stereochemistry of substrate 1 (Fig. 2). The largest deviation from Brønsted acid catalysis occurred with cis,anti-1, which gave a substantial percentage of cis-(BA)-3 and also a small amount of cis-(AB)-4 (Fig. 2a). The same trend, but less pronounced, was noted with the complementary trans,anti-1, which produced also small amounts of trans-(BA)-3 and trans-(AA)-5, formed instead of the inaccessible trans-(AB)-4 (see above, Fig. 2a).After investigation for anion transport, anion–π interactions have been introduced to catalysis in stabilizing anionic transition states on π-acidic surfaces.8,10 Over the past decade, catalysts from hexafluorobenzene to π-stacked foldamers, fullerenes, carbon nanotubes, artificial enzymes have been applied to many reactions, including enolate, enamine, imine, Diels–Alder chemistry.8 Polyether cyclizations have been introduced as a cascade transformation that should benefit best from the delocalized nature of anion–π interactions.10 On π-acidic surfaces, polyether cyclizations were autocatalytic,10 a unique emergent property that has not been observed in the many studies with systems without anion–π interactions.11With the privileged probe for supramolecular catalysis envisioned in this study, it was thus most interesting to assess the dependence of autocatalysis on the stereochemistry of the substrate. Significant dependence was conceivable considering the different products obtained from diastereomers of cis-1 with pnictogen-bonding catalyst 9 (Fig. 2a). Kinetics of all four test substrates converted with anion–π catalyst showed autocatalytic behavior (Fig. 5a and b). Moreover, autocatalysis was nearly independent of the stereochemistry of the substrate. This absence of diastereoselective autocatalysis was consistent with the computed model for transition-state stabilization by the product, and could explain why it is so difficult to achieve asymmetric autocatalysis on anion–π catalyst 10.13 Control experiments confirmed that general Brønsted acid catalysis does not show autocatalytic behavior, independent of the stereochemistry of substrate 1 (Fig. 5c and d).Open in a separate windowFig. 5Kinetics of the conversion of cis-1 (a and c, circles), cis,syn-1 (a and c, squares), trans-1 (b and d, circles) and trans,anti-1 (b and d, squares) with (a and b) anion–π catalyst 10 (10 mol%, rt) and (c and d) AcOH (500 mol%, 40 °C) in CD2Cl2, with hypothetical intermediate IX for autocatalysis on π-acidic surfaces.Taken together, the decoding of product fingerprints for cascade cyclizations that are simple enough to be tractable and complex enough to be interesting affords a privileged platform to characterize supramolecular catalysis. It is highly responsive to as many characteristics as possible, thus reporting on as many distinct advantages of the catalytic system as possible. The minimal substrate toolbox contains cis and trans di-epoxides as mixtures of syn–anti diastereomers, and at least one pure diastereomer. Most pairs of enantiomers are resolved in the chiral GC fingerprints. Applied to three model catalysts in comparison to general Brønsted acid catalysis, distinct fingerprints were found for all catalysts as well as for all different diastereomers of the substrate.In the cis series, most significant selectivity was observed with pnictogen-bonding catalysts, which give the unique AB product for anti and the more frequent BA product for the syn diastereomer of the diepoxide substrate with remarkably high selectivity. In the trans series, pnictogen-bonding catalysts broke the Baldwin rules most efficiently and independent of substrate stereochemistry, while within supramolecular capsules, completely new products were formed, including an interesting House–Meinwald rearrangement leading to cyclic hemiacetals. These distinct selectivities can be understood from the nature of the reactive intermediates. Together with particularly revealing details in the decoded product fingerprints, experimental support is obtained that the cascades are interconnected, possibly concerted. In clear contrast, anion–π catalysts gave mostly Baldwin products with fingerprints similar to general Brønsted acids. However, they showed unique autocatalytic behavior, a distinct emergent property that was independent of the stereochemistry of the substrate. All these distinctive characteristics found for representative supramolecular catalysts would be missed without the availability of decoded product fingerprints.These results thus validate the existence and significance of privileged substrate systems as general chemistry tools to characterize supramolecular catalysis. Once established, decoded polyether cascade fingerprints are very easy to use, ready to serve the community. For a new supramolecular catalyst to be characterized, the decoded fingerprints will reveal unique differences compared to controls. Importantly, because the system is hyperresponsive (Fig. 1a and and2a),2a), differences will be magnified. Due to the complexity required for hyperresponsiveness, the correlation of the fingerprint with the reactivity of a new catalyst will be mostly tentative and empirical at this point. For instance, AcOH-like fingerprints should reflect activation of epoxide opening to release the intramolecular leaving group, possibly supported by activation of the nucleophile as for autocatalysis on 10 (Fig. 5, IX). Fingerprints with more or even mostly A products should correlate with increasing SN1-like behavior. However, the generation of mostly B products with AcOH implies that the activation of epoxide opening needs to be supported by stabilization of the resulting carbocation with, e.g., cation–π interactions to afford A products. With pnictogen-bonding catalyst 9, this would be meaningful on the π-basic tetrachlorocatecholate plane next to the σ hole stabilizing the alcoholate (Fig. 2d). In fingerprints with the new HM-rearrangement products, so far unique for capsules 8, the existence of carbocation intermediates is experimentally confirmed and thus presumably most relevant, due to cation–π interactions, confinement effects, or both. From here, with the system trained with more and more fingerprints, the correlation of fingerprint with mechanism of a new catalyst should become increasingly informative. Sooner or later, this will enable high-level computational simulations at high confidence,7 which in turn will enhance the information on reactivity available from fingerprints of new catalysts. According to preliminary results on the difference between pnictogen-bonding and Lewis acid catalysis7 and the elucidation of more complex supramolecular systems,16 these future perspectives are most promising. 相似文献
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Chaohai Wang Hongyu Wang Jongbeom Na Yiyuan Yao Alowasheeir Azhar Xin Yan Junwen Qi Yusuke Yamauchi Jiansheng Li 《Chemical science》2021,12(46):15418
Heterogeneous Fenton-like processes are very promising methods of treating organic pollutants through the generation of reactive oxygen containing radicals. Herein, we report novel 0D–1D hybrid nanoarchitectonics (necklace-like structures) consisting of FeCo@N–C yolk–shell nanoreactors as advanced catalysts for Fenton-like reactions. Each FeCo@N–C unit possesses a yolk–shell structure like a nanoreactor, which can accelerate the diffusion of reactive oxygen species and guard the active sites of FeCo. Furthermore, all the nanoreactors are threaded along carbon fibers, providing a highway for electron transport. FeCo@N–C nano-necklaces thereby exhibit excellent performance for pollutant removal via activation of peroxymonosulfate, achieving 100% bisphenol A (k = 0.8308 min−1) degradation in 10 min with good cycling stability. The experiments and density-functional theory calculations reveal that FeCo dual sites are beneficial for activation of O–O, which is crucial for enhancing Fenton-like processes.Novel 0D–1D hybrid nanoarchitectonics consisting of FeCo@N–C yolk–shell nanoreactors are developed for Fenton-like reaction. With the multilevel advantages of this design, FeCo@N–C nano-necklaces exhibit excellent performance for BPA removal.Advanced oxidation processes (AOPs) are one of the most promising strategies to eliminate organic contaminants, sustainably generating reactive oxygen species (ROS) to ideally destroy all non-biodegradable, recalcitrant, toxic, or membrane-permeable organic impurities.1–4 Among these AOPs, sulfate radical (SO4˙−)-based Fenton-like processes have gained increasing attention as a water treatment strategy because of the strong oxidation potential of SO4˙− (3.1 V vs. normal hydrogen electrode) at wider pH ranges. SO4˙− is mainly produced by physical or chemical methods for activation of persulfate salts, such as peroxymonosulfate (PMS) and persulfate.5–9 Over the past two decades, heterogeneous catalysis has emerged as the most effective approach to water treatment, with much effort dedicated to developing better catalysts, including transition metal-based and carbonaceous materials.10,11 Unfortunately, most metal-based catalysts suffer from leaching of toxic metal ions, which can thwart their practical application,12,13 and although carbonaceous catalysts produce no secondary pollution, their cycle performance is always depressed.14 There is therefore an urgent need to find robust catalysts with adequate activity and stability for Fenton-like processes.To achieve superior performance, an ideal Fenton-like catalyst should contain oxidants with favorably reactive centers for cleavage of peroxyl bonds (O–O), have structure optimized for target pollutant attraction, and have chainmail to protect the vulnerable active sites for long periods.15–17 Recent studies have demonstrated Co–N–C active sites prefer to activate the O–O of PMS.18 Furthermore, introducing Fe-doping into the Co–N–C system not only suppresses Co2+ leaching, but also modulates the pyrrolic-N content, which is the adsorption site for capture of bisphenol A (BPA).19 We previously discovered that Co@C yolk–shell nanoreactors could enhance the catalytic activity because of the confinement effect in the nano-spaces between the core and shell, while the carbon shell acted like a chainmail protecting the Co active sites, keeping them highly reactive after five cycles.20,21Combining different kinds of materials to generate novel hybrid material interfaces can enable the creation of new kinds of chemical and physical functionalities that do not currently exist. However, one cannot simply mix these materials in an uncontrolled manner, because the ensemble of interfaces created by random mixing tends to favour thermodynamically stable interfaces that are functionally less active. Therefore, to prepare new materials with high functionality, it is necessary to carefully control the hybridization of components in interfacial regions with nanometric or atomic precision. By further hybridization of different components e.g., zero to one dimension (0D–1D) hybrid structures, we can prepare the structure to increase not only the specific surface area but also the interfacial region between different materials.In this work, we report novel 0D–1D hybrid nanoarchitectonics (necklace-like structures) consisting of FeCo@N–C yolk–shell nanoreactors as a PMS activator for Fenton-like processes. This catalyst has multilevel advantages: (i) each FeCo@N–C unit is a well-formed yolk–shell nanoreactor, which can guarantee sufficient contact of reactants and active sites, as well as defend them for good durability; (ii) all single nanoreactors are threaded along the carbon fibers, providing a highway for electron transport; and (iii) all the carbon fibers constructed into a thin film with macroscopic structure, which overcomes the complex recyclability of powder catalysts. Benefiting from favorable composition and unique structure, the FeCo@N–C catalyst delivers excellent performance for BPA removal via activation of PMS accompanied with good stability.The synthesis processes of necklace-like nanoarchitecture containing FeCo@N–C yolk–shell nanoreactors are illustrated in Fig. 1a. First, uniform Fe–Co Prussian blue analogue (Fe–Co PBA) nanocubes with an average size of 800–900 nm (Fig. 1b) are encapsulated in polyacrylonitrile (PAN) nanofibers by electrospinning. The obtained necklace-like FeCo PBA–PAN fibers (Fig. 1c) are then pyrolyzed at 800 °C in N2 atmosphere to produce FeCo@N–C nano-necklaces. The scanning electron microscopy (SEM) image (Fig. 1d) of the FeCo@N–C shows this necklace-like morphology with its large aspect ratio, with the FeCo@N–C particles strung along the PAN-derived carbon fibers. A broken particle (Fig. 1e) shows that the FeCo@N–C has a yolk–shell architecture, which is also identified by transmission electron microscopy (TEM). Fig. 1f and g show the well-defined space between the inner yolk and outer shell, which is attributed to the volume shrinkage of the original Fe–Co PBAs. During pyrolysis, Fe–Co PBA is reduced to FeCo (inner yolk) and PAN is carbonized (outer carbon shell), resulting in the unique necklace-like nanoarchitecture.22–24 The high-resolution TEM in Fig. 1h shows a lattice fringe of 0.20 nm, which matches well with the (110) plane of FeCo alloy.25 The scanning transmission electron microscopy (STEM) image (Fig. 1i) and corresponding elemental map (Fig. 1j) indicate that FeCo nanocrystals are well distributed in the inner core with some small FeCo nanocrystals located on external carbon shells. Furthermore, the control samples of Fe@N–C and Co@N–C nano-necklaces, prepared by only replacing the Fe–Co PBA nanocubes with Fe–Fe PB and Co–Co PBA (Fig. S1†), also demonstrate the versatility of this synthetic strategy. The formation of hierarchical porous structure, beneficial to the PMS transportation on the surface of catalysts, could be determined by N2 adsorption–desorption isotherms and corresponding pore volume analysis (Fig. S2 and Table S1†).Open in a separate windowFig. 1(a) Preparation of FeCo@N–C necklace-like nanoarchitecture. SEM images of (b) Fe–Co PBA cubic particles and (c) the electrospun FeCo PBA–PAN fibers. (d and e) SEM, (f and g) TEM, and (h) high-resolution TEM images of FeCo@N–C nano-necklaces. (i) STEM and (j) the corresponding elemental mappings of C, N, Fe, and Co.The X-ray diffraction patterns of the as-prepared products are depicted in Fig. S3,† with one prominent diffraction peak centered at 44.8° corresponding to the (110) lattice plane of FeCo alloy. All the products also have a characteristic signal at 26°, implying that graphite carbon is formed during pyrolysis. Raman spectroscopy further analyzed the crystal structures and defects of the FeCo@N–C nano-necklaces (Fig. S4†), where peaks found at 1349 cm−1 and 1585 cm−1 index the disordered (D band) and graphitic carbon (G band), respectively.26 X-ray photoelectron spectroscopy investigated the composition and valence band spectra of FeCo@N–C nano-necklaces. The survey spectrum (Fig. S5a†) reveals the presence of Fe (1.4%), Co (1.2%), C (86.4%), N (4.5%), and O (6.5%) in the composite. The high-resolution N 1s spectrum (Fig. S5b†) exhibits broad peaks at 398.1, 401.1, and 407.4 eV, corresponding to the pyridinic-N, graphitic-N, and σ* excitation of C–N, respectively.27 The high-resolution Fe 2p spectrum (Fig. S5c†) shows a broad peak at 707.4 eV, attributed to Fe0. Similarly, the 777.5 eV peak observed in the Co 2p spectrum (Fig. S5d†) corresponds to Co0, implying that FeCo dual sites have formed.28 The oxidation state of these sites was investigated by 57Fe Mössbauer spectroscopy, which found a sextet in the Mössbauer spectrum of the FeCo@N–C nano-necklaces attributed to FeCo dual sites (Fig. 2a and Table S2†).29 The coordination environment of the FeCo dual sites was also verified by X-ray absorption fine structure (XAFS) spectroscopy. Fig. 2b shows that the X-ray absorption near-edge structure (XANES) spectra of the Fe K-edge, which demonstrates a similar near-edge structure to that of Fe foil, illustrating that the main valence state of Fe in FeCo@N–C nano-necklaces is Fe0. Furthermore, the extended-XAFS (EXAFS) spectra (Fig. 2c) displays a peak at 1.7 Å, which is ascribed to the Fe–N bond, and a remarkable peak at approximately 2.25 Å corresponding to the metal–metal band.10,30 The Co K-edge and EXAFS spectra (Fig. S6†) also confirm the presence of Co–N and the metal–metal band. These results provide a potential structure of the FeCo dual sites in the FeCo@N–C nano-necklaces, as illustrated in Fig. 2d.Open in a separate windowFig. 2(a) 57Fe Mössbauer spectra of FeCo@N–C nano-necklaces at 298 K. (b) Fe K-edge XANES spectra of FeCo@N–C nano-necklaces and Fe foil. (c) Corresponding Fourier transformed k3-weighted of the EXAFS spectra for Fe K-edge. (d) Possible structure of the FeCo dual sites.This dual-metal center and necklace-like structure may be beneficial to enhance catalytic performance. Fig. 3a shows the Fenton-like performance for BPA degradation compared to Fe@N–C nano-necklaces, Co@N–C nano-necklaces, and FeCo@N–C particles (Fe–Co PBA directly carbonized without electrospinning). Here, the FeCo@N–C nano-necklaces display a higher catalytic performance, with BPA completely removed in 7 min. To clearly compare their catalytic behavior, the kinetics of BPA degradation was fitted by the first-order reaction. As shown in Fig. 3b, FeCo@N–C nano-necklaces exhibit the highest apparent rate constant (k = 0.83 min−1), which is approximately 6.4, 2.6, and 1.2 times that of FeCo@N–C particles, Fe@N–C nano-necklaces, and Co@N–C nano-necklaces, respectively. The significantly enhanced performance of FeCo@N–C nano-necklaces suggests that the FeCo dual sites and necklace-like nanoarchitecture are crucial. Furthermore, the concentration of BPA and PMS in the solution is higher than that in yolk–shell nanoreactor, resulting a concentration gradient which helps to accelerate the diffusion rates of reactants (Fig. 3c).31,32 For these nano-necklaces, the carbon shell acts like a chainmail protecting the FeCo active sites from attack by molecules and ions, and all the nanoreactors are threaded along the carbon fibers, providing a highway for electron transport, which is important for SO4˙− generation (SO4˙− production as eqn, HSO5− + e− → SO4˙− + OH−). Electrochemical impedance spectroscopy further confirms the good conductivity of the FeCo@N–C nano-necklaces (Fig. 3d). In addition, the concentration of metal-ion leaching and cycling performance (Fig. 3e and f) reveal the high reusability of FeCo@N–C nano-necklaces, with 95% BPA removal in 20 min after five cycles, which is also proved by the SEM and TEM characterization (Fig. S7†). The effect of other reaction parameters on the BPA degradation, such as pH, reaction temperature, PMS or catalysts dosage, and common anions, were investigated in detail (Fig. S8–S11†). All the results demonstrate that FeCo@N–C nano-necklaces deliver a better performance for PMS catalysis. In addition, the turnover frequency (TOF) value of FeCo@N–C nano-necklaces is 5.5 min−1 for BPA degradation, which is higher than many previously reported catalysts (detailed catalytic performance comparison as shown in Table S3†).Open in a separate windowFig. 3(a) BPA degradation efficiency in different reaction systems and (b) the corresponding reaction rate constants. (c) Schematic illustration of PMS activation in FeCo@N–C nano-necklaces. (d) Nyquist plots of the catalysts. (e) The metal leaching in different reaction systems. (f) Cycling performance of FeCo@N–C nano-necklaces for BPA removal. Reaction conditions: [catalyst] = 0.15 g L−1, [BPA] = 20 mg L−1, [PMS] = 0.5 g L−1, T = 298 K, and initial pH = 7.0.To examine the enhanced catalytic activity, radical quenching experiments were conducted. As shown in Fig. 4a, when NaN3 is added to the reaction solution as a scavenger for 1O2, there is no significant reduction of BPA decomposition, implying that non-radicals are not the dominant reactive species. By comparison, when tert-butanol (TBA) (radical scavenger for ˙OH) is added, there is a slight (2.8%) decrease in BPA removal. However, if methanol (radical scavenger for SO4˙− and ˙OH) is added, the efficiency of BPA degradation declines by up to 59.2%, indicating that the major radicals generated from the PMS activation are SO4˙−;33 the presence of these radicals is also verified by electron paramagnetic resonance (EPR) (Fig. 4b). Furthermore, the significant inhibition ratio can be observed when KI (quencher for the surface) is added, demonstrating that BPA degradation is mainly attributed to reactions with SO4˙−, which is produced by a surface catalytic process.34Open in a separate windowFig. 4(a) Effects of the radical scavengers on BPA degradation. (b) EPR spectra of SO4˙− and ˙OH. (c) The energy profiles of PMS on FeCo@N–C nano-necklaces surface. (d) Optimized configurations of PMS adsorbed on FeCo@N–C nano-necklaces.Density-functional theory was applied to calculate the surface energy of PMS activation at FeCo dual sites (Fig. 4c, d and S12†). The dissociation barrier of PMS into SO4˙− and OH− is −2.25 eV, which is much lower than that on an Fe or Co single site, suggesting that cleavage of O–O bonds of PMS occurs more easily on FeCo dual sites. This is because FeCo dual sites provide two anchoring sites for the dissociated O atoms, leading to more efficient activation of O–O. The FeCo@N–C nano-necklaces can reduce the energy barrier of O–O bond breaking, which results in high activity for PMS activation and thus high productivity of SO4˙−. 相似文献
9.
Isra S. Hassan Jack T. Fuller Vanessa
N. Dippon Angeline N. Ta Michael W. Danneman Brian R. McNaughton Anastassia N. Alexandrova Tomislav Rovis 《Chemical science》2022,13(32):9220
We report computationally-guided protein engineering of monomeric streptavidin Rh(iii) artificial metalloenzyme to enhance catalysis of the enantioselective coupling of acrylamide hydroxamate esters and styrenes. Increased TON correlates with calculated distances between the Rh(iii) metal and surrounding residues, underscoring an artificial metalloenzyme''s propensity for additional control in metal-catalyzed transformations by through-space interactions.We report computationally-guided protein engineering of monomeric streptavidin Rh(iii) artificial metalloenzyme to enhance catalysis of the enantioselective coupling of acrylamide hydroxamate esters and styrenes.Artificial metalloenzymes (ArMs) can be made by anchoring a non-natural (metal) cofactor into a protein scaffold, with the goal of imbuing new-to-nature reactivity.1 One of the most common ArM platforms is the biotin-tetrameric(strept)avidin (biotin-tSav) system pioneered by Whitesides and Ward.2,3 These ArMs utilize high-affinity (up to KD ∼10−14 M) interactions between tSav and biotin–metal conjugates. tSav-based ArMs have appeared in an increasing number of transition-metal catalyzed transformations.4–6 In collaboration with the Ward group, we have previously described a tetrameric streptavidin (tSav) system containing a biotinylated Rh(iii) cofactor for the asymmetric synthesis of dihydroisoquinolones using benzhydroxamate esters and acrylate partners.7 Monomeric streptavidin (mSav), a streptavidin/rhizavidin hybrid designed to resist tetramerization, retains its high affinity for biotin (KD ∼10−9 M).8,9 We recently described the use of mSav as a new ArM,10 whose simpler topology encourages protein engineering via a site-directed mutagenesis approach.Traditional manipulation of a metal''s reactivity has been accomplished by modification of the electronic and steric properties of the bound ligands (Fig. 1a).11,12 For example, we have documented and parsed the impact of Cp electronics and sterics on a number of Rh(iii) catalyzed transformations, by structural changes to the ligand in the primary coordination sphere of Rh.13 On the other hand, ArMs have traditionally been used as modifiers of a metal''s steric environment largely focusing on inducing asymmetry in the bond-forming events. Less broadly appreciated is the fact that any mutations in residues proximal to the active site may also impact the metal''s electronic properties via changes to the secondary coordination sphere (Fig. 1b), with the prospect of delivering more active catalysts for a given transformation.Open in a separate windowFig. 1Methods to modify the (a) primary and (b) secondary coordination sphere of a Rh(iii) catalyst.Previously, we described a mSav·Rh(iii) catalyst and demonstrated its use in the direct enantioselective coupling of acrylamide hydroxamate esters and styrenes.10 The reaction allows rapid access to piperidines – the most common N-heterocycle found in FDA-approved pharmaceuticals.14 One of the most interesting aspects of this reaction was our observation of a 7-fold increase in turnover number (TON) by embedding the cofactor into mSav''s active site.15 It has been a long-standing goal of ArMs to not only enable new-to-nature reactivity, but also for them to achieve the stellar kinetics of a native metalloenzyme. As these systems lack the evolutionary privilege of a natural metalloenzyme, extensive mutation of the protein scaffold may be required to find the optimal environment of the metal cofactor.Predicting the effects of specific mutations can prove very challenging, as any alterations to the protein conformation and charge distribution can impact reactivity regardless of the mutation''s distance from the active site.16–19 In order to design a better mutant, we embarked on a collaborative experimental and computational study to define the role of the protein scaffold and how single point mutations affect reactivity. We identified two key residues that play a pivotal role in mSav·Rh(iii) ArM''s secondary coordination sphere, and have used this insight to design a more active mutant.For the purposes of this study, we focused on the mSav·Rh(iii) ArM-catalyzed coupling of methacrylamide with 4-methoxystyrene as our model reaction (Fig. 2a). Using a small model of the catalyst, the lowest energy pathway of this reaction''s proposed mechanism was generated (Fig. S9†). The calculations were performed in Turbomole20–32 with the M06 density functional.33 Geometries were optimized with the def2-SVP basis set, and final electronic energies were calculated with the def2-TZVP basis set.34 The conductor-like screening model (COSMO)35 was used as implicit solvent with a dielectric of 80 to simulate water. These calculations predicted similar barriers for the N–H activation, the C–H activation, and the migratory insertion (differences less than 3 kcal mol−1). Isotope-exchange experiments revealed that the C–H activation step is reversible, implicating the migratory insertion step as turnover-limiting.10Open in a separate windowFig. 2(a) Model transformation. (b) Snapshot of the transition state for alkene insertion illustrating key nearby residues Y112 (red), E124 (blue), and S119 (purple). (c) Computed barrier to alkene insertion in the presence and absence of phenol and acetate (shown in blue).The Cp* moiety of the Cp*biotinRhX2 cofactor is non-covalently localized in the active site likely due to a π–π stacking interaction with Y112 (Fig. 2b). This assignment is supported by the observation that mutant Y112A leads to lower yield and enantioselectivity.10 We hypothesized that we could further manipulate both the sterics and electronics of the Cp* moiety by either directly mutating Y112 or indirectly by mutating other residues that affect the Y112-Cp* interaction.To generate a model of mSav''s protein scaffold and active-site we used QM/DMD36 – a hybrid quantum mechanics/molecular mechanics method that simulates proteins piecewise. Discrete molecular dynamics (DMD) equilibrates the entire system except for the metal and part of the substrate.36 After a trajectory of ∼0.5 ns, quantum mechanics (QM) is used to optimize the metal region plus sidechains and residues immediately surrounding it. This process is repeated, providing efficient sampling of the entire protein scaffold while treating the metal environment quantum-mechanically. For this study, the migratory insertion transition state was modeled in WT by freezing the coordinates of the rhodium atom and the two carbon atoms forming a bond. For each system, five replicate simulations were run for ∼20 ns each.Residues E124 and S119 both hydrogen bond to Y112 and are in close proximity to the RhCp* catalytic site (Fig. 2b).37 To estimate the electronic effects of these three residues on the reaction, an acetate ion, methanol molecule, and 4-methylphenol (p-cresol) molecule were added to a small catalyst model without constraints but initially positioned to mimic the sidechains of these residues (Fig. 2c). The migratory insertion energy barrier decreases by 2 kcal mol−1 with incorporation of the three residues. However, this energy barrier decreases by an additional 3 kcal mol−1 upon the deletion of the methanol molecule representing S119. Not only does this imply that these amino acid sidechains may be the primary reason for the increased activity of the protein-installed catalyst, but also suggest that a longer Y112–S119 distance is favorable, so long as no water can insert in this region and replace S119 in its H-bond with Y112. We hypothesize that the carboxylate group of E124 acts as a hydrogen bond acceptor, donating electron density to the Y112 phenol ring, which in turn donates electron density to the catalyst via π–π charge transfer. This could enhance the electron donation of the metal and decrease the energy barrier to the migratory insertion step. On the other hand, S119 acts as a hydrogen bond donor which would remove electron density from Y112 and subsequently the Rh(iii) moiety.Unfortunately, mutation of Y112 (Y112F and Y112W) results in negligible protein yields. We thus identified three flanking residues (T111, E113, H87) that may be expected to have a significant impact on Y112''s position, and one distal (T32) residue, chosen as distal mutations sometimes have significant impact (Fig. 3). Through this subset of mutants, we attempted to increase TON and establish a correlation between the Y112–Rh distance and Y112–S119 distance of the mutants and their reactivities.Open in a separate windowFig. 3Structure of mSav from two different views highlighting some of the mutated residues including their TON and enantioselectivity.We used QM/DMD to simulate a representative set of these mutants spanning a wide range of TONs measured in the experiment. The Y112–Rh and Y112–S119 distances were measured every ∼0.5 ps for every simulation. The results can be represented by a 3-dimensional plot with Y112–Rh distance on the X axis, Y112–S119 distance on the Y axis, and probability density on the Z axis (Fig. 4). We find the best correlation between TON and probability density in the conformational region where the Y112–Rh distance is the shortest and the Y112–S119 interaction is not energetically relevant.38Open in a separate windowFig. 4Three-dimensional probability distributions from select mutants by simultaneous sampling of Rh–Y112 and S119–Y112 distances. Probabilities for the outlined regions are also shown.To clarify this correlation, we calculated the probability of having a Y112–S119 distance between 3.5–6 Å and a Y112–Rh distance less than 5.65 Å. This Y112–S119 distance corresponds to negligible hydrogen bonding.39 Additionally, we constrained the small model catalyst shown in Fig. 5b (ref. 40) and calculated the corresponding energy barriers at different Y112–Rh distances (Fig. 5a). Since rate increases exponentially as the barrier decreases,35 differences in probabilities in the region where the Y112–Rh distance is between 5.4–5.65 Å have the greatest impact on the relative TONs of our model methacrylamide styrene coupling. We conclude that mutants with increasing probability in this region provide increasing TON.Open in a separate windowFig. 5a) Theoretical dependence of migratory insertion barrier on Rh-phenol distance. (b) Small-model catalyst.Theoretically, a shorter Y112–Rh distance relative to WT would result in increased reactivity. Residue G49 is located under the Rh(iii) moiety (Fig. 6). We hypothesize that by mutating the glycine into an alanine, steric congestion would force the biotinylated Rh(iii) cofactor to shift upwards closer to the electron donating phenol side chain of residue Y112. Analyzing the critical portions of the Y112–Rh and Y112–S119 distances in tandem reveals that G49A has the highest probability density in this region (Fig. 4). Indeed, experimentally, this mutant gives 97 TON and 91% ee (Fig. 6). The combination of a short Y112–Rh distance and long Y112–S119 distance leads to an increase in reactivity. This is an approximate 3-fold improvement in the TON relative to WT. The G49A mutant serves as an experimental proof of concept that a computational analysis of an ArMs secondary coordination sphere can lead to the design of a more efficient ArM.Open in a separate windowFig. 6Snapshot of the transition state for alkene insertion highlighting the position of G49 (purple) relative to Rh. Y112 is shown in red and E124 is shown in blue.In summary, we have identified three key residues that contribute to accelerating the rate of a Rh(iii)-catalyzed reaction by electronic communication to the metal via the secondary coordination sphere. E124 hydrogen bonds to Y112 transferring electron density via π–π charge transfer, an effect that is attenuated by hydrogen bonding from S119. Optimal interaction of these residues can be described computationally by finding mutants that have multiple conformations bearing short Y112–Rh distances coupled with negligible bonding between Y112 and S119. This hypothesis was experimentally verified by a mutant that enforces a closer Y112–Rh distance leading to improved TON. This result demonstrates the use of a hypothesis-based site-directed mutagenesis of the secondary sphere residues, to optimize the metal''s electronic environment within the protein scaffold and enhance an ArM''s activity. 相似文献
10.
Zishi Zhang Chaohai Wang Yiyuan Yao Hao Zhang Jongbeom Na Yujun Zhou Zhigao Zhu Junwen Qi Miharu Eguchi Yusuke Yamauchi Jiansheng Li 《Chemical science》2022,13(32):9159
The organized assembly of nanoparticles into complex macroarchitectures opens up a promising pathway to create functional materials. Here, we demonstrate a scalable strategy to fabricate macroarchitectures with high compressibility and elasticity from hollow particle-based carbon nanofibers. This strategy causes zeolitic imidazolate framework (ZIF-8)-polyacrylonitrile nanofibers to assemble into centimetre-sized aerogels (ZIF-8/NFAs) with expected shapes and tunable functions on a large scale. On further carbonization of ZIF-8/NFAs, ZIF-8 nanoparticles are transformed into a hollow structure to form the carbon nanofiber aerogels (CNFAs). The resulting CNFAs integrate the properties of zero-dimensional hollow structures, one-dimensional nanofibers, and three-dimensional carbon aerogels, and exhibit a low density of 7.32 mg cm−3, high mechanical strength (rapid recovery from 80% strain), outstanding adsorption capacity, and excellent photo-thermal conversion potential. These results provide a platform for the future development of macroarchitectured assemblies from nanometres to centimetres and facilitate the design of multifunctional materials.A scalable strategy is established to generate macroarchitectures based on MOF-related nanofibers. The modular assembly of macroarchitectures with luffa-like structures exhibits high mechanical strength and low densities.The assembly of simple nanoparticles (such as silica, polystyrene and metal–organic frameworks) into macroarchitectures has a unique attraction for engineering materials due to their variable sizes, shapes, and chemical and physical properties.1–3 As a novel nanomaterial, the formed macroarchitecture with three-dimensional (3D) porous interconnected network structures has broad application prospects in various fields, including environment treatment, chemical sensing, energy storage, catalysis, and advanced electronic devices.4–7 Moreover, the functions of macroarchitectures are mainly determined by the fundamental building blocks. On account of large surface area, high porosity and more exposure to active sites, the complex macroarchitectures, which are assembled by building blocks with hollow structures, possess greater advantages.8,9In the past few decades, in order to seek high-performance hollow building blocks for macroarchitectures, much effort has been put into it. In particular, the emergence of one-dimensional (1D) carbon hollow nanostructures, including hollow porous carbon nanofibers (HPCNs)10 and carbon nanotubes (CNTs)11 promotes the rapid development of this field. The HPCN- and CNT-based macroarchitectures realize the transformation from 1D nanomaterials to three-dimensional (3D) macroscopic materials with excellent properties (e.g., electrochemical energy storage and antimicrobial air filtration).12,13 Furthermore, these macroarchitectures can not only retain the characteristics of the 1D material, but also generate many new kinds of features (e.g., high specific surface area, high mechanical strength, and low density) that the components do not possess. Unfortunately, though the HPCN- and CNT-based macroarchitectures exhibit improved conductivity and stability properties, the synthesis of their building blocks is usually expensive and complex.14 Besides, the assembly of building blocks into 3D macroarchitectures usually exhibits relatively poor mechanical properties and requires some adhesives or templates, which have to be eliminated by extra strategies.15 These complex synthetic procedures and less favourable structural stability largely hinder the scale-up production of carbon aerogels and their practical applications.To address these issues, we explore a novel and scalable method to synthesize functional macroarchitectures with robust mechanical properties fabricated from MOF-derived carbon nanofibers through manipulating nano-sized particles (MOFs) and micron-sized fibers. First, zeolitic imidazolate framework (ZIF-8) nanoparticles, which are spectacular for their large nitrogen content and surface area,16–18 are embedded into polyacrylonitrile (PAN)/polyvinylpyrrolidone (PVP) nanofibers to form ZIF-8-PAN/PVP composite nanofibers. Subsequently, the ZIF-8-PAN/PVP nanofibers are assembled into centimetre-sized nanofiber aerogels (ZIF-8/NFAs) by a freeze-drying technique. After preoxidation and carbonization of ZIF-8/NFAs, the carbon nanofiber aerogels with hollow and porous interlayer structures are fabricated (named C-ZIF-8-CNFAs). The interlayer structure of C-ZIF-8-CNFAs is very similar to natural luffa consisting of a network of elastic frameworks. As with the interconnected nanofibers in the interlayer structure, cellulose skeletons are in the interior of luffa interconnected in a highly uniform manner to maximize strength, a porous structure. Therefore, we refer to our porous structure as luffa-like. The prepared C-ZIF-8-CNFAs exhibit a low density of 7.32 mg cm−3, high specific surface area (288 m2 g−1), large hierarchical pore volume (0.22 cm−3 g−1), high mechanical strength (rapid recovery from 80% strain), outstanding adsorption capacity, and excellent photo-thermal conversion potential. Fig. 1a depicts the assembly strategy of macroarchitectures (C-ZIF-8-CNFAs) schematically. The preparation process begins with the fabrication of ZIF-8/nanofibers (Fig. S1b†) using the method that ZIF-8 nanoparticles (Fig. S1a†) are incorporated into nanofibers by electrospinning (specific preparation methods in the ESI†). Upon homogenization in a mixed solution of ultrapure water and tert-butanol, the ZIF-8/nanofibers become wrapped around each other and dispersed uniformly. Subsequently, the homogenized nanofiber dispersion is frozen in a mold followed by freeze-drying into uncrosslinked ZIF-8/NFAs. To build further robust bonding among nanofibers, the obtained uncrosslinked ZIF-8/NFAs are preoxidized at 250 °C to form crosslinked ZIF-8/NFAs with a welding structure under the action of polyvinylpyrrolidone (PVP), providing elastic resilience to the resultant NFAs. Ultimately, the resulting preoxidized ZIF-8/NFAs are carbonized at 900 °C to form hollow C-ZIF-8-CNFAs under a N2 atmosphere. As a result of the carbonization, the organic ligands of ZIF-8 and molecules of PAN and PVP are decomposed and transformed into N-doped carbon materials. In addition, the Zn2+ in ZIF-8 nanoparticles is reduced to metallic Zn and then evaporated at high temperature.19–21 Nanoscale 0D MOFs are assembled into micron-scale 1D fibers, which are then assembled into centimeter-scale 3D carbon aerogels (Fig. 1b). This novel approach enables the super assembly on a multi-dimensional scale, which realizes the macroscopic application of nanoparticles and the functionalization of CAs. In order to verify that the performance of C-ZIF-8-CNFAs is improved after the introduction of ZIF-8, pure CNFAs (Fig. S2†) without ZIF-8 (the synthetic process is shown in the ESI†) are also prepared.Open in a separate windowFig. 1Preparation steps for C-ZIF-8-CNFAs. (a) More fabrication details for C-ZIF-8-CNFAs. (b) Schematic illustration of the fabrication of CNFAs.As illustrated in Fig. 2a, when the ZIF-8/nanofiber dispersion solution is frozen, the uniformly dispersed ZIF-8/nanofibers are extruded by the growth of ice crystals and assembled among ice crystals. After the sample is frozen completely, the nanofibers become lapped and locked into a 3D nanofibrous network. Subsequently, the ZIF-8/NFAs with a luffa-like structure are obtained after the sublimation of ice crystals through the freeze-drying process.22 Moreover, ZIF-8/NFAs can be made into diverse desired shapes such as cylinders, cubes, moon-like shapes, star-like shapes, heart-like shapes and intricate shapes of the letters (Fig. 2b). Fig. 2c shows the obvious reduction of the intensity of ZIF-8/NFA XRD patterns compared to the original ZIF-8, but the site hardly changes, which confirms that the introduced ZIF-8 nanoparticles are not destroyed during the electrospinning and the preparation process of aerogels. After the preoxidation and carbonization steps, the typical C-ZIF-8-CNFAs with an ultra-low density of 7.32 mg cm−3 can freely stand on the tip of a red maple leaf (Fig. 2b). The scanning electron microscopy (SEM) images in Fig. 2d–f show that C-ZIF-8-CNFAs have the hierarchical porous luffa-like structure with three kinds of pores (the picture of an actual luffa shown in the inset of Fig. 2d). The porous structure exhibits obvious rectangular pores of ∼25 μm, and the wall of these pores is made of interconnecting nanofibers (Fig. 2e). Meanwhile, the secondary pores of ∼1.5 μm are formed by the welded nanofibers that are interconnected with each other. The nanoscale pores of ∼200 nm also exist in these nanofibers, which come from the carbonization of ZIF-8 nanoparticles (Fig. 2f). As observed from the magnified SEM image (Fig. S3†), the welded structure resulting from preoxdiation is still preserved through carbonization. Remarkably, ZIF-8 nanoparticles encapsulated by PAN and PVP are transformed into a hollow structure after carbonization. As can be seen from the TEM image (Fig. 2g), the ZIF-8-derived hollow structure is evenly dispersed in PAN/PVP-derived carbon nanofibers. Because Zn2+ ions coordinate with –C N groups existing on the surface of PAN/PVP nanofibers, the ZIF-8 particles become tightly encapsulated by the PAN/PVP layers. During carbonization, the PAN/PVP layers make ZIF-8 shrink from inside to outside, thereby leading to the generation of a hollow structure. Moreover, the confined carbonization process within the PAN/PVP matrix prevents the irreversible fusion and aggregation of carbonized ZIF-8 nanoparticles.19Open in a separate windowFig. 2(a) Schematical illustration of the formation principles for the hierarchical cellular structure. (b) Photographs of ZIF-8/NFAs with diverse shapes and the lightweight C-ZIF-8-CNFAs standing on the tip of a red maple leaf. (c) Wide-angle XRD patterns. (d–g) SEM (d–f) and TEM (g) images showing the microstructure of C-ZIF-8-CNFAs at various magnifications. (h and i) N2 adsorption–desorption isotherm and pore-size distribution curve of CNFAs and C-ZIF-8-CNFAs.After ZIF-8 nanoparticles were introduced into CNFAs, the properties have been improved significantly. To comprehend the variation of the porous characteristics in C-ZIF-8-CNFAs, nitrogen (N2) adsorption–desorption measurements were carried out. As observed from Fig. 2h and i, C-ZIF-8-CNFAs have a larger specific surface area of 288.3 m2 g−1 and pore volume of 0.22 cm−3 g−1, while the specific surface area and pore volume of CNFAs are only 12.1 m2 g−1 and 0.01 cm−3 g−1, respectively. Meanwhile, C-ZIF-8-CNFAs also have a hierarchical porous structure with micropores, mesopores, and macropores (Fig. 2i). Because of the existence of the hierarchical porous structure in C-ZIF-8-CNFAs, they have a lower density relative to CNFAs (20.73 mg cm−3) (Table S1†). The chemical compositions and graphitic structure of C-ZIF-8-CNFAs are investigated by X-ray powder diffraction (XRD) and X-ray photoelectron spectroscopy (XPS). The XRD pattern (Fig. S4a†) of C-ZIF-8-CNFAs only exhibits two broad peaks at about 25° and 44°, corresponding to the (002) and (101) diffraction facets of the graphitic structure, respectively.23 The correlative XPS spectrum shows that C-ZIF-8-CNFAs consist of C, N and O (Fig. S4b†). The high-resolution N 1s spectra (Fig. S4c†) can be deconvoluted into four peaks: pyridinic N (398.6 eV), pyrrolic N (399.4 eV), graphitic N (400.9 eV), and oxidized N (403.7 eV), respectively. The percentage of nitrogen and its types are listed in Table S2.† There is no Zn content thus indicating that it had evaporated during the carbonization process at high temperature (at 900 °C for 3 hours).24 Furthermore the N content of C-ZIF-8-CNFAs increases with the introduction of ZIF-8 compared to CNFAs clearly (Table S3†).In stark contrast to the hard and brittle characteristics of conventional carbon aerogels, C-ZIF-8-CNFAs show robust mechanical properties, sustaining large compressive strain without fracture (insets in Fig. 3a and movie S1†). The compressive stress–strain (σ–ε) curves (Fig. 3a) show the compressive process of C-ZIF-8-CNFAs and two typical deformation regimes could be recognized: a Hookean or linear elastic regime of ε < 50% with a stable tangent modulus, and a densification regime of ε > 50% with σ and dσ/dε increasing sharply. When the maximum compressive strain increases from 30% to 80%, the maximum compressive stress steeply increases from 1.2 to 25.9 kPa, indicating that C-ZIF-8-CNFAs can bear over 25 000 times their own weight without cracking. Moreover, the cyclic compression test of the C-ZIF-8-CNFAs is performed to validate their durable cycling performance by applying 50 loading–unloading fatigue cycles at a large ε of 50% (Fig. 3b). C-ZIF-8-CNFAs hardly undergo plastic deformation at all after the 50th cycle, which is a huge improvement over traditional CAs with a crisp character. As shown in Fig. 3c, C-ZIF-8-CNFAs retain nearly 100% of the initial value of the Young''s modulus, maximum stress and energy loss coefficient, indicating that their strength or stiffness has no significant decline highlighting their exceptional structural robustness. Two reasons could account for the excellent mechanical elasticity of C-ZIF-8-CNFAs. On the one hand, the compressive strain is absorbed by the bending of the connected ZIF-8/nanofibers between layers; on the other hand, the strain that continues to grow (beyond 50%) is absorbed by the densification of minor pores, which is formed by the welding of PVP (Fig. 3d).25 The two reasons can also be confirmed by the sharp increase of the compressive stress after ε > 50% (Fig. 3a).Open in a separate windowFig. 3(a) Compressive stress–strain curve of C-ZIF-8-CNFAs at different strains. The insets are photographs of C-ZIF-8-CNFAs under a compressing and releasing cycle (ε = 80%). (b) A 50-cycle compressive fatigue test with ε of 50%. (c) The Young''s modulus, energy loss coefficient, and maximum stress versus compressive cycles. (d) Sketch of the changes in the hierarchical porous structure with compressive deformation.MOF-based derived CNFAs with hollow structures, ultra-low density, extraordinary mechanical elasticity, and large surface area are conducive to applications in various fields, including environment governance, energy absorption, and energy storage.26–28 As a proof of concept, we evaluated the organic solvent absorption and photo-thermal conversion performance of C-ZIF-8-CNFAs. Excellent hydrophobicity is one of the important factors to ensure the absorption efficiency of organic solvents. As demonstrated in Fig. 4a, C-ZIF-8-CNFAs exhibit high hydrophobicity with a water contact angle of 142° and the water contact angle has no significant change after 120 s. The water droplet and the absorbed oil droplet are on the surface of C-ZIF-8-CNFAs, indicating the effective oil/water selectivity of C-ZIF-8-CNFAs (Fig. S5†). As shown in Fig. 4b, C-ZIF-8-CNFAs demonstrate extraordinary absorption capacities for common oils and various organic solvents, 90–200 times their own weight, principally depending on the density and viscosity of the solvents. For example, the adsorption capacity for carbon tetrachloride (ρ = 1.595 g cm−3) is much higher than the adsorption capacity for n-hexane (ρ = 0.66 g cm−3). We also compared the maximum adsorption capacity of C-ZIF-8-CNFAs and CNFAs for several common organic solvents and oils. The adsorption performance of C-ZIF-8-CNFAs is also demonstrated to be better than that of CNFAs (Fig. S6†). According to the cross-sectional diagram of the adsorption of organic solvents (Fig. 4c), CNFAs only absorb organic solvents through the capillary phenomenon of the channel, which is formed by nanofibers, while the absorbed organic solvent can also enter into the hollow structure formed by carbonization of ZIF-8 inside the nanofiber of C-ZIF-8-CNFAs. Therefore, the performance of C-ZIF-8-CNFAs is significantly improved after the addition of ZIF-8 nanoparticles. Moreover, the adsorption capacity of C-ZIF-8-CNFAs for organic solvents is greater than that of previously reported aerogels (Fig. S7†). To verify the excellent adsorption performance of C-ZIF-8-CNFAs in practical application, the oil/water separation and cyclic adsorption experiments were carried out. As illustrated in Fig. S8,† C-ZIF-8-CNFAs can quickly absorb heavy organic solvents such as carbon tetrachloride (dyed with oil red) sunk at the bottom of water, thus indicating their potential application for selectively removing oils from water. Recyclability and reusability are also crucial to evaluate the practical application possibility of adsorption materials. In view of the outstanding elasticity and structural robustness of C-ZIF-8-CNFAs, we chose ethanol as the absorption solvent for recycling tests. Through simple heating, ethanol absorbed by C-ZIF-8-CNFAs can be readily removed. As demonstrated in Fig. S9a and b,† even after 10 cycles, C-ZIF-8-CNFAs still retained over 90% adsorption capacity for ethanol and their mass was reduced by less than 10%.Open in a separate windowFig. 4(a) Dynamic behaviors of a water droplet on the surface of C-ZIF-8-CNFAs. (b) Adsorption efficiency of C-ZIF-8-CNFAs towards commonly used organic solvents and oils. (c) Schematic illustration of the organic solvent adsorption process inside the CNFAs and C-ZIF-8-CNFAs. (d) Mass changes of evaporated water versus time under 1 sun illumination. (e) The temperature of C-ZIF-8-CNFAs and seawater under 1 sun illumination as a function of irradiation time. (f) The infrared images (IR) show the temperature distribution of C-ZIF-8-CNFAs and seawater under 1 sun illumination with an irradiation time of 0, 30, and 60 min.Given the abundant porous structure and blackbody characteristic, C-ZIF-8-CNFAs are also promising materials for interfacial solar steam generation (ISSG). To investigate the ISSG performance, the evaporation mass change of seawater and C-ZIF-8-CNFAs is measured under one sun illumination. As shown in Fig. 4d, the seawater in C-ZIF-8-CNFAs achieves the maximum evaporation rate of 3.74 kg m−2 h−1, which is 5.12 times the evaporation rate of bulk seawater (0.73 kg m−2 h−1) and 2.34 times faster than the evaporation rate of general 2D ISSG (∼1.6 kg m−2 h−1). An infrared camera is used to trace the surface temperatures of C-ZIF-8-CNFAs and bulk seawater under one-sun illumination to evaluate the photothermal behavior of ISSG (Fig. 4e). The surface temperature of C-ZIF-8-CNFAs presents a quick increase in 5 min and eventually reaches a stable state (∼48 °C) after 10 min, while the bulk seawater temperature stays unchanged (∼25 °C). The consecutive infrared images in Fig. 4f show the equilibrium temperature distribution and heat localization effect of C-ZIF-8-CNFAs and bulk seawater in 60 min under one-sun illumination. 相似文献
11.
Gulsen Turkoglu Gozde Kayadibi Koygun Mediha Nur Zafer Yurt Seyda Nur Pirencioglu Sundus Erbas-Cakmak 《Chemical science》2021,12(28):9754
A molecular keypad lock that displays photodynamic activity when exposed to glutathione (GSH), esterase and light in the given order, is fabricated and its efficacy in drug resistant MCF7 cancer cells is investigated. The first two inputs are common drug resistant tumor markers. GSH reacts with the agent and shifts the absorption wavelength. Esterase separates the quencher from the structure, further activating the agent. After these sequential exposures, the molecular keypad lock is exposed to light and produces cytotoxic singlet oxygen. Among many possible combinations, only one ‘key’ can activate the agent, and initiate a photodynamic response. Paclitaxel resistant MCF7 cells are selectively killed. This work presents the first ever biological application of small molecular keypad locks.Information processing therapeutics with an implemented keypad lock logic gate selects input order for activation in drug resistant cancer cells.The complex nature of diseases such as cancer necessitates smarter drugs that can discriminate each disease state or regulate drug efficacy spatially and/or temporally. With this intention, activatable drugs, drugs with on demand release properties are developed with promising selectivity.1–4 Information processing therapeutics which are based on molecular logic gate operations are another approach to solve this problem.5–7 Molecular logic gates are small compounds using Boolean logic operations to process inputs (i.e. the analyte concentration), and give an output as a result (fluorescence, and therapeutic activity etc.).8 Selective drug activation, release, multiple-analyte sensing and theranostic applications of these devices have been explored by us and others.5,9–19Among the operations that can be carried out using small molecules, keypad locks provide an alternative application in information security.20 This logic operation can give a specific output when the inputs are given in the correct form and correct sequence. For the device, each input is considered as an AND logic operation where the history of the process is also considered. A pioneering example was reported by Margulies and Shanzer in 2007 where energy transfer is modulated by chelation of Fe3+ in a pH dependent manner.21 Later, various other devices were introduced with advanced properties such as more than 2 input responsiveness and error detection capability.22–24 All-photonic logic gates to address chemical waste production is extensively studied by Gust, Andréasson and Pischel.25,26 Beside small molecule keypad locks, enzymes, antibodies, and DNA hybrids are used to achieve the same goal.27–30 Although their potential use in molecular cryptology is highlighted, so far, there is no solid biological application of small molecule keypad locks.In the research presented here, a molecular keypad lock is developed which displays a photodynamic therapeutic output when a molecule is exposed to analytes in the correct order and type (PS3, Fig. 1). Two inputs of the system are chosen to be the common markers of drug resistant tumours: glutathione (GSH) and esterase enzyme (E). Cancer cells develop resistance to traditional chemotherapy in time by changing the protein expression or metabolite content of the cell. This adaptation of cancer cells is an obstacle for their treatment and needs to be addressed. Glutathione is a tripeptide used in reductive biochemical synthesis and it is known to be present in elevated levels in rapidly dividing cells such as cancer cells.31 A high GSH level is reported to contribute to drug resistance, since GSH adducts of the drugs are exported out of the cell much more rapidly.32,33 Likewise, esterase enzyme activity is known to be associated with drug detoxification as this enzyme contributes to the chemical conversion of the drug.34,35 Glutathione and esterase enzyme are chosen to be the first two inputs of the molecular keypad lock, the first two digits of the password. In the research, light is used as the final input. Although trivial, light is essential for photodynamic activity and spatiotemporal control of irradiation, further improving selectivity of the therapy.Open in a separate windowFig. 1Chemical structures of model photosensitizers (PS1 and PS2) and a molecular keypad lock (PS3). Ester bonds (red) are prone to hydrolysis by the esterase enzyme. Distyryl sites of the photosensitizers (blue) can react with thiol nucleophile provided that it is bound to an electron deficient group (i.e. pyri-dinium).Keypad lock PS3 is a photodynamic therapy (PDT) agent. PDT is a non-invasive method used for the treatment of surface cancers and certain other diseases ranging from atherosclerosis to macular degeneration.36–39 In this therapy, a photosensitizer is excited with light, and produces cytotoxic singlet oxygen (1O2) thereby triggering apoptosis or necrosis of the cell, initiating an immune response and blocking microvasculature.40 In the research, a boradiazaindecene (BODIPY) photosensitizer is used to benefit from versatile chemistry and spectroscopic properties.41–45Near-IR absorbing PS3 shown in Fig. 1 is the molecular keypad lock and it is synthesized in 13 steps (Scheme S1†). PS3 and model compound PS2 have heavy atoms on the structure to favour intersystem crossing required for transition to the triplet state and hence 1O2 generation occurs.43 Ester bonds on the structure of PS3 are prone to cleavage by esterase enzyme. Distryryl bonds on the PS3 (blue) tend to reduce or form an adduct with thiol nucleophiles when it is activated by the pyridinium electron withdrawing group.46 This property lies at the heart of sequential operation of esterase and GSH. When GSH reacts with electron poor double bonds, the extended conjugated structure is broken and PS3-a is generated (Fig. 2). This structure has absorption below 550 nm, like brominated core BODIPY molecules (compound 8, Scheme S1†), and therefore can be excited with a green light. A quencher (green) is attached to ensure that photodynamic activity is OFF until esterase cleaves the ester bond. This is because of the energy transfer from the photosensitizer to this module, until esterase separates the photosensitizer. Since PS3 lacks absorption around the 500–550 nm region, it is inactive until GSH reacts with the compound. However, the GSH reacted photosensitizer does show absorption in this region; so, in order to avoid full activation just by GSH, a quencher module is attached. Spectral overlap between the BODIPY core (see the structure of compound 8 in the ESI,† similar to that of PS3-a in terms of conjugation) and quencher (Q) can be seen from UV-Vis absorption and fluorescence spectra (Fig. 3 and S1†). By this way, the photosensitizer is chemically modulated by GSH to ensure excitation, and then esterase enzyme inhibits energy transfer by removing the quencher. Lastly a green light is used to excite the photosensitizer leading to generation of photodynamic action. Since light is necessary for the final excitation of the molecule, it should always be the last input. If the order of esterase and GSH changes, as shown in Fig. 2, activation is not expected to take place since cleavage of the ester bonds generates 4-hydroxybenzyl derivative on PS3, which spontaneously faces 1,4-elimination to generate pyridine (Fig. S2†).47 Pyridine on its own is not sufficiently electron withdrawing to favour nucleophilic attack of double bonds by GSH and to activate it as demonstrated below. Therefore, the photosensitizer preserves extended conjugation and essentially lacks absorption at the wavelength of excitation.Open in a separate windowFig. 2Sequential operation of GSH and esterase. GSH can only react with BODIPY distyryl units when the structure has electron withdrawing pyridinium, either reducing it or forming an adduct. Esterase enzyme cleaves ester bonds, liberating the photosensitizer from the quencher module (green). Initial esterase activity converts the pyridinium unit to pyridine, thereby decreasing the reactivity of double bonds with GSH.Open in a separate windowFig. 3Normalized UV-Vis absorption and fluorescence spectra of PS1–3 in 2% water in THF (a and b). Samples are excited at 600 nm. Spectral changes of PS3 (10 μM) alone (black) or PS3 upon exposure to 0.5 mM GSH (c) and 10U esterase (d) for 90 min and 60 min at 37 °C, in 2% water in THF, respectively. A new peak at 544 nm appears upon incubation with GSH which is attributed to reduced PS3 and/orthe GSH-adduct. Esterase treatment increases the relative intensity of the shoulder peak around 600 nm.In order to understand the response of the PS3 to GSH, a molecule is incubated with 0.5 mM of GSH at 37 °C for 90 min. A new peak at 544 nm appears in UV-Vis absorption spectra consistent with the hypothesis (Fig. 3c, S1 and S9†). The formation of the GSH adduct (PS3-a) is demonstrated by Liquid Chromatography Mass spectrometry analysis (Fig. S3†). When control module PS1 is exposed to the same conditions, this new peak is not detected indicating that the pyridine bearing structure is neither activated enough for the nucleophilic substitution by GSH nor did it display PDT activity (Fig. S4 and S5†). On the other hand, GSH treated pyridinium bearing PS2 immediately displayed a colour change indicative of broken conjugation (Fig. S6†). When PS3 is incubated with esterase for 1 h, a small hypsochromic shift in the absorption peak is detected as a shoulder to the parent peak which is attributed to the conversion of pyridinium to pyridine (PS3-c, Fig. 3d). The control PS3 sample which is incubated under the same conditions but lacks esterase does not show an enhancement of this peak (Fig. 3d, black). High Resolution Mass Spectrometry analysis of the esterase treated PS2 samples confirm the hydrolysis of the ester and subsequent formation of the pyridine compound (Fig. S7†). Esterase treated samples display an increase in the emission intensity when excited at 620 nm (Fig. S8†). This is attributed to the initial quenching of the quencher module by the pyridinium photosensitizer. Analysis of the absorption and emission spectra suggest that the quencher module of PS3 can induce energy transfer to the pyridinium photosensitizer (Fig. 3). Once separated by esterase, fluorescence of the quencher module increases. In the case of GSH treated sample, a small enhancement in emission upon excitation at 500 nm is observed (Fig. S9†). Note that the GSH adduct (or PS3 with reduced double bonds) has higher absorption at this wavelength, which would be the reason for the increase in emission intensity. In the spectral analysis organic solvents with a low water content are used to monitor the formation of water-insoluble, neutral, pyridine-bearing intermediate species.In the project, the molecular keypad lock is aimed to unlock in the presence of drug resistant tumour markers and get activated. Activation cannot take place when the input order differs. To demonstrate this, photodynamic action in the presence of all three inputs in a different order is investigated. 1O2 production can be followed by using trap molecule, 1,3-diphenylisobenzofuran (DPBF).48 This molecule reacts with 1O2 and loses its absorption at 418 nm. The effect of different input combinations on the PDT action are given in Fig. 4. In the first 15 min, all samples are kept in the dark. Under such conditions no 1O2 generation is detected, which indicates lack of dark activity. DPBF is exposed to light from a LED source (peak 505 nm) under the same experimental conditions and no decrease in the absorption is detected. This control experiment eliminates the photodegradation of DPBF in the absence of a photosensitizer. Upon irradiation before the activation of the photosensitizer by GSH and esterase, no 1O2 generation is observed as expected. The results show that 1O2 generation, and the subsequent decrease in DPBF absorption, are significantly more in the input order of glutathione, esterase enzyme and light, consistent with the proposed mode of activation.Open in a separate windowFig. 4 1O2 generation ability of PS3 (0.1 μM) when three inputs are given in a different order. All samples contain 50 μM of 1O2 trap molecule DPBF. In the first 15 minutes samples are kept in the dark. GSH is added in 0.5 mM concentration and incubated for 90 min at 37 °C. Samples are incubated with 10U esterase for 1 h at 37 °C. An LED light is irradiated from a 30 cm distance for 45 min.To analyse the effect of PDT action in the cell, a drug resistant cell line is generated. MCF7 cells are exposed to an increased dose of traditional cancer therapeutic agent paclitaxel as described in the literature.49 When the spindle-shaped morphology is obtained following maximum drug dose application, cells are reported to have drug resistance. At this stage, PS3 is applied to both normal and drug resistant cells. When cell viabilities at various concentrations are analysed, it has been found that the light toxicity of PS3 is significantly enhanced in drug resistant cells (Fig. 5). The IC50 values of irradiated samples are calculated to be 124.8 μM for MCF7 cells. This value is reduced to 52.5 μM in paclitaxel resistant MCF7 (Pac-MCF7) indicating improved cytotoxicity in these cells. Efficient induction of apoptosis is also proved by Annexin V and PI staining (Fig. 6). Under dark conditions, cells do not have significant loss of viability. Upon irradiation, resistant cells are more prone to apoptosis by the photosensitizer. Relative singlet oxygen generation abilities and results of cell culture experiments altogether confirm selective activation in drug resistant cells.Open in a separate windowFig. 5Change in the cell viability of normal and paclitaxel resistant MCF7 cells (Pac-MCF7) in the presence of PS3 at various concentrations. For each group, cell viability is analysed both after incubation in the dark or after irradiation with a 505 nm LED light source from a distance of 10 cm. Average values of three independent experiments are used.Open in a separate windowFig. 6Apoptosis induction by PS3 (25 μM) in normal and paclitaxel resistant MCF7 cancer cells under dark conditions and upon irradiation with a 505 nm LED light from 10 cm distance. Scale bars: 50 μm. 相似文献
12.
Nathan Corbin Deng-Tao Yang Nikifar Lazouski Katherine Steinberg Karthish Manthiram 《Chemical science》2021,12(38):12847
Correction for ‘Suppressing carboxylate nucleophilicity with inorganic salts enables selective electrocarboxylation without sacrificial anodes’ by Nathan Corbin et al., Chem. Sci., 2021, DOI: 10.1039/D1SC02413B.We regret that there was a minor error in the structure of the benzyl chloride in Scheme 2, Fig. 2 and the ESI. The structure of the benzyl chloride should be 4-methyl benzyl chloride but was instead given as 3-methyl benzyl. The correct figure and scheme are shown below, and the ESI has been updated.Open in a separate windowFig. 2(A) Comparison of acid yields for non-sacrificial-anode and sacrificial-anode carboxylation of various substrates. (B) Ratio of carboxylic acid to nucleophilic side products (ester + carbonate + alcohol) for various systems and substrates. Effect of adding MgBr2 to the sacrificial-anode system on the (C) acid yield and (D) ratio of acid to SN2 side products for benzyl bromide. Acid yields are tabulated in Table S6.† ND: acid not detected (acid-to-SN2 ratio <0.1).Open in a separate windowScheme 2Substrate scope for the sacrificial-anode-free electrochemical carboxylation of organic halides. aStandard reaction conditions: 100 mM electrolyte, 100 mM substrate, 100 mM MgBr2, silver cathode, platinum anode, 20 sccm CO2, 2.2 mL DMF, −20 mA cm−2 for 3.5 h. TBA-Br was used for chlorinated substrates because bromide oxidizes more readily than chloride, and only a small amount of chloride was replaced by bromide (<1% for the alkyl chloride, ∼4% for the benzylic chloride). Yields are referenced to the initial amount of substrate and were calculated from 1H NMR spectroscopy using either 1,3,5-trimethoxybenzene or ethylene carbonate as internal standards. b−15 mA cm−2 instead of −20 mA cm−2. c150 mM MgBr2 instead of 100 mM MgBr2.The Royal Society of Chemistry apologises for these errors and any consequent inconvenience to authors and readers. 相似文献
13.
Multisubstituted pyrroles are important fragments that appear in many bioactive small molecule scaffolds. Efficient synthesis of multisubstituted pyrroles with different substituents from easily accessible starting materials is challenging. Herein, we describe a metal-free method for the preparation of pentasubstituted pyrroles and hexasubstituted pyrrolines with different substituents and a free amino group by a base-promoted cascade addition–cyclization of propargylamides or allenamides with trimethylsilyl cyanide. This method would complement previous methods and support expansion of the toolbox for the synthesis of valuable, but previously inaccessible, highly substituted pyrroles and pyrrolines. Mechanistic studies to elucidate the reaction pathway have been conducted.This method is a toolbox for the synthesis of valuable, but previously inaccessible, highly substituted pyrroles and pyrrolines.Pyrroles are molecules of great interest in a variety of compounds including pharmaceuticals, natural products and other materials. Pyrrole fragments for example are key motifs in bioactive natural molecules, forming the subunit of heme, chlorophyll and bile pigments, and are also found in many clinical drugs, including those in Fig. 1a.1 Although many classical methods of pyrrole synthesis, including the Paal–Knorr condensation,2 the Knorr reaction,3 the Hantzsch reaction,4 transition metal-catalyzed reactions,5 and multicomponent coupling reactions,6 have been developed over many years, the efficient synthesis of multisubstituted pyrroles is still challenging. In condensation syntheses of pyrroles, the major problems lie in the extended syntheses of complex precursors and limited substitution patterns that are allowed. Multicomponent reactions are superior when building pyrrole core structures with more substituents. Among these, the [2+2+1] cycloaddition reaction of alkynes and primary amines is attractive because of the readily available alkyne and amine substrates and the ability to construct fully substituted pyrroles.7 However, with the exception of some rare examples,8 most [2+2+1] cycloaddition reactions afford pyrroles with two or more identical substituents. The synthesis of multisubstituted pyrroles with all different substituents from simple starting materials therefore remains a major challenge.Open in a separate windowFig. 1Previous reports and this work on propargylamides transformation.Easily accessible propargylamides are classical, privileged building blocks broadly utilized for the synthesis of a large variety of heterocyclic molecules such as pyrroles, pyridines, thiazoles, oxazoles and other relevant organic frameworks.9 For example, Looper10et al. reported the synthesis of 2-aminoimidazoles from propargyl cyanamides and Eycken11 reported a method starting from propargyl guanidines which undergo a 5-exo-dig heterocyclization as shown in Fig. 1b. Subsequently, Wan12et al. revealed the cyclization of N-alkenyl propargyl sulfonamides into pyrroles via sulfonyl migration. Inspired by these transformations and multi-substituted pyrrole synthesis, we report herein a direct synthesis of pentasubstituted pyrroles and hexasubstituted pyrrolines with all different substituents from propargyl sulfonylamides and allenamides.Previously, Zhu,13 Ji14 and Qiu13b,15 reported efficient syntheses of 2-aminopyrroles from isocyanides. Ye16 and Huang17 independently developed gold-catalyzed syntheses of 2-amino-pentasubstituted pyrroles with ynamides. Despite the many advantages of these methods, they all afford protected amines, rather than free amines. The deprotection of these amines may cause problems in further transformations of the products. Our method delivers pyrroles with an unprotected free amino group and are often complementary to the previously well-developed classical methods.Initially, the cyclization reaction of N-(1,3-diphenylprop-2-yn-1-yl)-N-ethylbenzenesulfonamide (1a) with trimethylsilyl cyanide (TMSCN) was carried out with Ni(PPh3)2Cl2 as a catalyst, a base (Cs2CO3) and DMF as a solvent. Different metal catalysts, such as Ni(PPh3)2Cl2, Pd(OAc)2, Cu(OAc)2, and Co(OAc)2 provided the desired product with similar yields ( Entry Cat. Base Solvent Yield 1 Ni(PPh3)2Cl2 Cs2CO3 DMF 67% 2 Pd(OAc)2 Cs2CO3 DMF 65% 3 Cu(OAc)2 Cs2CO3 DMF 65% 4 Co(OAc)2 Cs2CO3 DMF 63% 5 Cs2CO3 DMF 65% 6 KF DMF Trace 7 K3PO4 DMF Trace 8 K2CO3 DMF 48% 9 KOH DMF 52% 10 KOtBu DMF 46% 11 Et3N DMF Trace 12 Cs2CO3 CH3CN 18% 13 Cs2CO3 DME 23% 14 Cs2CO3 Toluene Trace 15 Cs2CO3 DCE Trace 16 Cs2CO3 Dioxane Trace