Computational study of the mechanism and selectivity of ruthenium-catalyzed hydroamidations of terminal alkynes

Density functional theory calculations were performed to elucidate the mechanism of the ruthenium-catalyzed hydroamidation of terminal alkynes, a powerful and sustainable method for the stereoselective synthesis of enamides. The results provide an explanation for the puzzling experimental finding that with tri-n-butylphosphine (P(Bu)₃) as the ligand, the E-configured enamides are obtained, whereas the stereoselectivity is inverted in favor of the Z-configured enamides with (dicyclohexylphosphino)methane (dcypm) ligands. Using the addition of pyrrolidinone to 1-hexyne as a model reaction, various pathways were investigated, among which a catalytic cycle turned out to be most advantageous for both ligand systems that consists of: (a) oxidative addition, (b) alkyne coordination, (c) alkyne insertion (d) vinyl-vinylidene rearrangement, (e) nucleophilic transfer and finally (f) reductive elimination. The stereoselectivity of the reaction is decided in the nucleophilic transfer step. For the P(ⁿBu)₃ ligand, the butyl moiety is oriented anti to the incoming 2-pyrolidinyl unit during the nucleophilic transfer step, whereas for the dcypm ligand, steric repulsion between the butyl and cyclohexyl groups turns it into a syn orientation. Overall, the formation of E-configured product is favorable by 4.8 kcal mol^–1 (Δ^‡ GSDL) for the catalytic cycle computed with P(Bu)₃ as ancillary ligand, whereas for the catalytic cycle computed with dcypm ligands, the Z-product is favored by 7.0 kcal mol^–1 (Δ^‡ GSDL). These calculations are in excellent agreement with experimental findings.     

A hexanuclear gold carbonyl cluster

The hexanuclear gold carbonyl cluster [PPh₄]₂[Au₆(CF₃)₆Br₂(CO)₂] (4) has been obtained by spontaneous self-assembly of the following independent units: CF₃AuCO (1) and [PPh₄][Br(AuCF₃)₂] (3). The cyclo-Au₆ aggregate 4, in which the components are held together by unassisted, fairly strong aurophilic interactions (Au···Au ∼310 pm), exhibits a cyclohexane-like arrangement with chair conformation. These aurophilic interactions also result in significant ν(CO) lowering: from 2194 cm^–1 in the separate component 1 to 2171 cm^–1 in the mixed aggregate 4. Procedures to prepare the single-bridged dinuclear component 3 as well as the mononuclear derivative [PPh₄][CF₃AuBr] (2) are also reported.     

Wide bandgap OPV polymers based on pyridinonedithiophene unit with efficiency >5%

We report the properties of a new series of wide band gap photovoltaic polymers based on the N-alkyl 2-pyridone dithiophene (PDT) unit. These polymers are effective bulk heterojunction solar cell materials when blended with phenyl-C₇₁-butyric acid methyl ester (PC₇₁BM). They achieve power conversion efficiencies (up to 5.33%) high for polymers having such large bandgaps, ca. 2.0 eV (optical) and 2.5 eV (electrochemical). Grazing incidence wide-angle X-ray scattering (GIWAXS) reveals strong correlations between π–π stacking distance and regularity, polymer backbone planarity, optical absorption maximum energy, and photovoltaic efficiency.     

Tuning π-Acceptor/σ-Donor Ratio of the 2-Isocyanoazulene Ligand: Non-Fluorinated Rival of Pentafluorophenyl Isocyanide and Trifluorovinyl Isocyanide Discovered

Isocyanoazulenes (CNAz) constitute a relatively new class of isocyanoarenes that offers rich structural and electronic diversification of the organic isocyanide ligand platform. This article considers a series of 2-isocyano-1,3-X₂-azulene ligands (X = H, Me, CO₂Et, Br, and CN) and the corresponding zero-valent complexes thereof, [(OC)₅Cr(2-isocyano-1,3-X₂-azulene)]. Air- and thermally stable, X-ray structurally characterized 2-isocyano-1,3-dimethylazulene may be viewed as a non-benzenoid aromatic congener of 2,6-dimethyphenyl isocyanide (2,6-xylyl isocyanide), a longtime “workhorse” aryl isocyanide ligand in coordination chemistry. Single crystal X-ray crystallographic {Cr–CNAz bond distances}, cyclic voltametric {E_1/2(Cr^0/1+)}, ¹³C NMR {δ(¹³CN), δ(¹³CO)}, UV-vis {dπ(Cr) → pπ*(CNAz) Metal-to-Ligand Charge Transfer}, and FTIR {ν_N≡C, ν_C≡O, k_C≡O} analyses of the [(OC)₅Cr(2-isocyano-1,3-X₂-azulene)] complexes provided a multifaceted, quantitative assessment of the π-acceptor/σ-donor characteristics of the above five 2-isocyanoazulenes. In particular, the following inverse linear relationships were documented: δ(¹³CO_trans) vs. δ(¹³CN), δ(¹³CO_cis) vs. δ(¹³CN), and δ(¹³CO_trans) vs. k_C≡O,trans force constant. Remarkably, the net electron withdrawing capability of the 2-isocyano-1,3-dicyanoazulene ligand rivals those of perfluorinated isocyanides CNC₆F₅ and CNC₂F₃.     

Kinetic Study of the Oxidative Addition Reaction between Methyl Iodide and [Rh(imino-β-diketonato)(CO)(PPh)3] Complexes,Utilizing UV–Vis,IR Spectrophotometry,NMR Spectroscopy and DFT Calculations

The oxidative addition of methyl iodide to [Rh(β-diketonato)(CO)(PPh)₃] complexes, as modal catalysts of the first step during the Monsanto process, are well-studied. The β-diketonato ligand is a bidentate (BID) ligand that bonds, through two O donor atoms (O,O-BID ligand), to rhodium. Imino-β-diketones are similar to β-diketones, though the donor atoms are N and O, referred to as an N,O-BID ligand. In this study, the oxidative addition of methyl iodide to [Rh(imino-β-diketonato)(CO)(PPh)₃] complexes, as observed on UV–Vis spectrophotometry, IR spectrophotometry and NMR spectrometry, are presented. Experimentally, one isomer of [Rh(CH₃COCHCNPhCH₃)(CO)(PPh₃)] and two isomers of [Rh(CH₃COCHCNHCH₃)(CO)(PPh₃)] are observed—in agreement with density functional theory (DFT) calculations. Experimentally the [Rh(CH₃COCHCNPhCH₃)(CO)(PPh₃)] + CH₃I reaction proceeds through one reaction step, with a rhodium(III)-alkyl as the final reaction product. However, the [Rh(CH₃COCHCNHCH₃)(CO)(PPh₃)] + CH₃I reaction proceeds through two reaction steps, with a rhodium(III)-acyl as the final reaction product. DFT calculations of all the possible reaction products and transition states agree with experimental findings. Due to the smaller electronegativity of N, compared to O, the oxidative addition reaction rate of CH₃I to the two [Rh(imino-β-diketonato)(CO)(PPh)₃] complexes of this study was 7–11 times faster than the oxidative addition reaction rate of CH₃I to [Rh(CH₃COCHCOCH₃)(CO)(PPh₃)].     

Synthesis,Structure, and Photophysical Properties of Yellow-Green and Blue Photoluminescent Dinuclear and Octanuclear Copper(I) Iodide Complexes with a Disilanylene-Bridged Bispyridine Ligand

The synthesis, structural, and photophysical investigations of CuI complexes with a disilanylene-bridged bispyridine ligand 1 are herein presented. Dinuclear (2) and ladder-like (3) octanuclear copper(I) complexes were straightforwardly prepared by exactly controlling the ratio of CuI/ligand 1. Single-crystal X-ray analysis confirmed that dinuclear complex 2 had no apparent π…π stacking whereas octanuclear complex 3 had π…π stacking in the crystal packing. In the solid state, the complexes display yellow-green (λ_em = 519 nm, Φ = 0.60, τ = 11 µs, 2) and blue (λ_em = 478 nm, Φ = 0.04, τ = 2.6 µs, 3) phosphorescence, respectively. The density functional theory calculations validate the differences in their optical properties. The difference in the luminescence efficiency between 2 and 3 is attributed to the presence of π…π stacking and the different luminescence processes.     

Accelerating the insertion reactions of (NHC)Cu–H via remote ligand functionalization

Most ligand designs for reactions catalyzed by (NHC)Cu–H (NHC = N-heterocyclic carbene ligand) have focused on introducing steric bulk near the Cu center. Here, we evaluate the effect of remote ligand modification in a series of [(NHC)CuH]₂ in which the para substituent (R) on the N-aryl groups of the NHC is Me, Et, ^tBu, OMe or Cl. Although the R group is distant (6 bonds away) from the reactive Cu center, the complexes have different spectroscopic signatures. Kinetics studies of the insertion of ketone, aldimine, alkyne, and unactivated α-olefin substrates reveal that Cu–H complexes with bulky or electron-rich R groups undergo faster substrate insertion. The predominant cause of this phenomenon is destabilization of the [(NHC)CuH]₂ dimer relative to the (NHC)Cu–H monomer, resulting in faster formation of Cu–H monomer. These findings indicate that remote functionalization of NHCs is a compelling strategy for accelerating the rate of substrate insertion with Cu–H species.

Remote modification of an N-heterocyclic carbene ligand with bulky or electron-rich groups in [(NHC)Cu(μ-H)]₂ increases the rate of substrate insertion, which kinetics studies suggest arises from changes in the Cu–H monomer–dimer equilibrium.     

Cobalt-catalysed asymmetric hydrovinylation of 1,3-dienes

In the presence of bidentate 1,n-bis-diphenylphosphinoalkane-CoCl₂ complexes {Cl₂Co[P ∼ P]} and Me₃Al or methylaluminoxane, acyclic (E)-1,3-dienes react with ethylene (1 atmosphere) to give excellent yields of hydrovinylation products. The regioselectivity (1,4- or 1,2-addition) and the alkene configuration (E- or Z-) of the resulting product depend on the nature of the ligand and temperature at which the reaction is carried out. Cobalt(ii)-complexes of 1,1-diphenylphosphinomethane and similar ligands with narrow bite angles give mostly 1,2-addition, retaining the E-geometry of the original diene. Complexes of most other ligands at low temperature (–40 °C) give almost exclusively a single branched product, (Z)-3-alkylhexa-1,4-diene, which arises from a 1,4-hydrovinylation reaction. A minor product is the linear adduct, a 6-alkyl-hexa-1,4-diene, also arising from a 1,4-addition of ethylene. As the temperature is increased, a higher proportion of the major branched-1,4-adduct appears as the (E)-isomer. The unexpectedly high selectivity seen in the Co-catalysed reaction as compared to the corresponding Ni-catalysed reaction can be rationalized by invoking the intermediacy of an η⁴-[(diene)[P ∼ P]CoH]⁺-complex and its subsequent reactions. The enhanced reactivity of terminal E-1,3-dienes over the corresponding Z-dienes can also be explained on the basis of the ease of formation of this η⁴-complex in the former case. The lack of reactivity of the X₂Co(dppb) (X = Cl, Br) complexes in the presence of Zn/ZnI₂ makes the Me₃Al-mediated reaction different from the previously reported hydroalkenylation of dienes. Electron-rich phospholanes, bis-oxazolines and N-heterocyclic carbenes appear to be poor ligands for the Co(ii)-catalysed hydrovinylation of 1,3-dienes. An extensive survey of chiral ligands reveals that complexes of DIOP, BDPP and Josiphos ligands are quite effective for these reactions even at –45 °C and enantioselectivities in the range of 90–99% ee can be realized for a variety of 1,3-dienes. Cobalt(ii)-complex of an electron-deficient Josiphos ligand is especially active, requiring only <1 mol% catalyst to effect the reactions.     

Cluster Compounds with Oxidised,Hexanuclear [Nb6Cli 12Ia 6] n− Anions (n=2 or 3)

Four mixed‐halide cluster salts with chloride‐iodide‐supported octahedral Nb₆ metal atoms cores were prepared and investigated. The cluster anions have the formula [Nb₆Clⁱ ₁₂I^a ₆] ⁿ⁻ with Cl occupying the inner ligand sites and I the outer one. They are one‐ or two‐electron‐oxidized (n=2 or 3) with respect to the starting material cluster. (Ph₄P)⁺ and (PPN)⁺ function as counter cations. The X‐ray structures reveal a mixed occupation of the outer sites for only one compound, (PPN)₃[Nb₆Clⁱ ₁₂I^a _5.047(9)Cl^a _0.953]. All four compounds are obtained in high yield. If in the chemical reactions a mixture of acetic anhydride, CH₂Cl₂, and trimethylsilyl iodide is used, the resulting acidic conditions lead to form the two‐electron‐oxidised species (n=2) with 14 cluster‐based electrons (CBEs). If only acetic anhydride is used, the 15 CBE species (n=3) is obtained in high yield. Interesting intermolecular bonding is found in (Ph₄P)₂[Nb₆Clⁱ ₁₂I^a ₆] ⋅ 4CH₂Cl₂ with I⋅⋅⋅I halogen bonding and π‐π bonding interactions between the phenyl rings of the cations in (PPN)₃[Nb₆Clⁱ ₁₂I^a _5.047(9)Cl^a _0.953]. The solubility of (Ph₄P)₂[Nb₆Clⁱ ₁₂I^a ₆] ⋅ 4CH₂Cl₂ has been determined qualitatively in a variety of solvents, and good solubility in the aprotic solvents CH₃CN, THF and CH₂Cl₂ has been found.     

Square-Planar Heteroleptic Complexes of α-Diimine-NiII-Catecholate Type: Intramolecular Ligand-to-Ligand Charge Transfer

Two heteroleptic Ni^II complexes combined the redox-active catecholate and 2,2′- bipyridine ligand platforms were synthesized to observe a photoinduced intramolecular ligand-to-ligand charge transfer (LL’CT, HOMO_catecholate → LUMO_α-diimine). A molecular design of compound [Ni^II(3,6-Cat)(bipy)]∙CH₃CN (1) on the base of bulky 3,6-di-tert-butyl-o-benzoquinone (3,6-DTBQ) was an annelation of the ligand with an electron donor glycol fragment, producing derivative [Ni^II(3,6-Cat^gly)(bipy)]∙CH₂Cl₂ (2), in order to influence the energy of LL’CT transition. A substantial longwave shift of the absorption peak was observed in the UV-Vis-NIR spectra of 2 compared with those in 1. In addition, the studied Ni^II derivatives demonstrated a pronounced negative solvatochromism, which was established using a broad set of solvents. The molecular geometry of both compounds can be ascribed as an insignificantly distorted square-planar type, and the π–π intermolecular stacking of the neighboring α-diimines is realized in a crystal packing. There is a lamellar crystal structure for complex 1, whereas the perpendicular T-motifs with the inter-stacks attractive π–π interactions form the packing of complex 2. The redox-active nature of ligand systems was clearly shown through the electrochemical study: a quasi-reversible one-electron reduction of 2,2′-bipyridine and two reversible successive one-electron oxidative conversations (“catecholate dianion—o-benzosemiquinonato radical anion—neutral o-benzoquinone”) were detected.     

Theoretical prediction of a graphene-like 2D uranyl material with p-orbital antiferromagnetism

Versatile graphene-like two-dimensional materials with s-, p- and d-block elements have aroused significant interest because of their extensive applications while there is a lack of such materials with f-block elements. Herein we report a unique one composed of the f-block element moiety of uranyl (UO₂²⁺) through a global-minimum structure search. Its geometry is found to be similar to that of graphene with a honeycomb-like hexagonal unit composed of six uranyl ligands, where each uranyl is bridged by two superoxido groups and a pair of hydroxyl ligands. All the uranium and bridging oxygen atoms form an extended planar 2D structure, which shows thermodynamic, kinetic and thermal stabilities due to σ/π bonding as well as electrostatic interactions between ligands. Each superoxido ligand has one unpaired (2p_π*)¹ electron and is antiferromagnetically coupled through uranyl bridges with 2p_π*–5f_δ–2p_π* superexchange interactions, forming a rare type of one-dimensional Heisenberg chain with p-orbital antiferromagnetism, which might become valuable for application in antiferromagnetic spintronics.

An unprecedented graphene-like 2D uranyl material with p-orbital antiferromagnetism is found to be stable by computational investigations.     

1,2-Addition and cycloaddition reactions of niobium bis(imido) and oxo imido complexes

The bis(imido) complexes (BDI)Nb(N^tBu)₂ and (BDI)Nb(N^tBu)(NAr) (BDI = N,N′-bis(2,6-diisopropylphenyl)-3,5-dimethyl-β-diketiminate; Ar = 2,6-diisopropylphenyl) were shown to engage in 1,2-addition and [2 + 2] cycloaddition reactions with a wide variety of substrates. Reaction of the bis(imido) complexes with dihydrogen, silanes, and boranes yielded hydrido-amido-imido complexes via 1,2-addition across Nb-imido π-bonds; some of these complexes were shown to further react via insertion of carbon dioxide to give formate-amido-imido products. Similarly, reaction of (BDI)Nb(N^tBu)₂ with tert-butylacetylene yielded an acetylide-amido-imido complex. In contrast to these results, many related mono(imido) Nb BDI complexes do not exhibit 1,2-addition reactivity, suggesting that π-loading plays an important role in activating the Nb–N π-bonds toward addition. The same bis(imido) complexes were also shown to engage in [2 + 2] cycloaddition reactions with oxygen- and sulfur-containing heteroallenes to give carbamate- and thiocarbamate-imido complexes: some of these complexes readily dimerized to give bis-μ-sulfido, bis-μ-iminodicarboxylate, and bis-μ-carbonate complexes. The mononuclear carbamate imido complex (BDI)Nb(NAr)(N(^tBu)CO₂) (12) could be induced to eject tert-butylisocyanate to generate a four-coordinate terminal oxo imido intermediate, which could be trapped as the five-coordinate pyridine or DMAP adduct. The DMAP adducted oxo imido complex (BDI)NbO(NAr)(DMAP) (16) was shown to engage in 1,2-addition of silanes across the Nb-oxo π-bond; this represents a new reaction pathway in group 5 chemistry.

Another slice of pi: the addition of a second π-donor ligand engenders 1,2-addition and [2 + 2] cycloaddition reactivity across Nb-imido and Nb-oxo bonds.     

Synthesis of New Functionally Substituted 9-Azabicyclo[4.2.1]nona-2,4,7-trienes by Cobalt(I)-Catalyzed [6π + 2π]-Cycloaddition of N-Carbocholesteroxyazepine to Alkynes

Catalytic [6π + 2π]-cycloaddition of N-carbocholesteroxyazepine with functionally substituted terminal alkynes and 1,4-butynediol was performed for the first time under the action of the Co(acac)₂(dppe)/Zn/ZnI₂ three-component catalytic system. The reaction gave previously undescribed but promising 9-azabicyclo[4.2.1]nona-2,4,7-trienes (in 79–95% yields), covalently bound to a natural metabolite, cholesterol. The structure of the synthesized azabicycles was confirmed by analysis of one- and two-dimensional (¹H, ¹³C, DEPT ¹³C, COSY, NOESY, HSQC, HMBC) NMR spectra.     

Toxic Effect of Fullerene and Its Derivatives upon the Transmembrane β2-Adrenergic Receptors

Numerous experiments have revealed that fullerene (C₆₀) and its derivatives can bind to proteins and affect their biological functions. In this study, we explored the interaction between fullerine and the β₂-adrenergic receptor (β₂AR). The MD simulation results show that fullerene binds with the extracellular loop 2 (ECL2) and intracellular loop 2 (ICL2) of β₂AR through hydrophobic interactions and π–π stacking interactions. In the C₆₀_in1 trajectory, due to the π–π stacking interactions of fullerene molecules with PHE and PRO residues on ICL2, ICL2 completely flipped towards the fullerene direction and the fullerene moved slowly into the lipid membrane. When five fullerene molecules were placed on the extracellular side, they preferred to stack into a stable fullerene cluster (a deformed tetrahedral aggregate), and had almost no effect on the structure of β₂AR. The hydroxyl groups of fullerene derivatives (C₆₀(OH)_X, X represents the number of hydroxyl groups, X = 4, 8) can form strong hydrogen bonds with the ECL2, helix6, and helix7 of β₂AR. The hydroxyl groups firmly grasp the β₂AR receptor like several claws, blocking the binding entry of ligands. The simulation results show that fullerene and fullerene derivatives may have a significant effect on the local structure of β₂AR, especially the distortion of helix4, but bring about no great changes within the overall structure. It was found that C₆₀ did not compete with ligands for binding sites, but blocked the ligands’ entry into the pocket channel. All the above observations suggest that fullerene and its derivatives exhibit certain cytotoxicity.     

Ligand and solvent effects on CO2 insertion into group 10 metal alkyl bonds

The insertion of carbon dioxide into metal element σ-bonds is an important elementary step in many catalytic reactions for carbon dioxide valorization. Here, the insertion of carbon dioxide into a family of group 10 alkyl complexes of the type (^RPBP)M(CH₃) (^RPBP = B(NCH₂PR₂)₂C₆H₄⁻; R = Cy or ^tBu; M = Ni or Pd) to generate κ¹-acetate complexes of the form (^RPBP)M{OC(O)CH₃} is investigated. This involved the preparation and characterization of a number of new complexes supported by the unusual ^RPBP ligand, which features a central boryl donor that exerts a strong trans-influence, and the identification of a new decomposition pathway that results in C–B bond formation. In contrast to other group 10 methyl complexes supported by pincer ligands, carbon dioxide insertion into (^RPBP)M(CH₃) is facile and occurs at room temperature because of the high trans-influence of the boryl donor. Given the mild conditions for carbon dioxide insertion, we perform a rare kinetic study on carbon dioxide insertion into a late-transition metal alkyl species using (^tBuPBP)Pd(CH₃). These studies demonstrate that the Dimroth–Reichardt parameter for a solvent correlates with the rate of carbon dioxide insertion and that Lewis acids do not promote insertion. DFT calculations indicate that insertion into (^tBuPBP)M(CH₃) (M = Ni or Pd) proceeds via an S_E2 mechanism and we compare the reaction pathway for carbon dioxide insertion into group 10 methyl complexes with insertion into group 10 hydrides. Overall, this work provides fundamental insight that will be valuable for the development of improved and new catalysts for carbon dioxide utilization.

The kinetics of carbon dioxide insertion into a pincer-supported palladium methyl complex are studied. The complex inserts carbon dioxide at room temperature, and we explore both solvent and Lewis acid effects on carbon dioxide insertion.     

Cooperative B–H bond activation: dual site borane activation by redox active κ2-N,S-chelated complexes

Cooperative dual site activation of boranes by redox-active 1,3-N,S-chelated ruthenium species, mer-[PR₃{κ²-N,S-(L)}₂Ru{κ¹-S-(L)}], (mer-2a: R = Cy, mer-2b: R = Ph; L = NC₇H₄S₂), generated from the aerial oxidation of borate complexes, [PR₃{κ²-N,S-(L)}Ru{κ³-H,S,S′-BH₂(L)₂}] (trans–mer-1a: R = Cy, trans–mer-1b: R = Ph; L = NC₇H₄S₂), has been investigated. Utilizing the rich electronic behaviour of these 1,3-N,S-chelated ruthenium species, we have established that a combination of redox-active ligands and metal–ligand cooperativity has a big influence on the multisite borane activation. For example, treatment of mer-2a–b with BH₃·THF led to the isolation of fac-[PR₃Ru{κ³-H,S,S′-(NH₂BSBH₂N)(S₂C₇H₄)₂}] (fac-3a: R = Cy and fac-3b: R = Ph) that captured boranes at both sites of the κ²-N,S-chelated ruthenacycles. The core structure of fac-3a and fac-3b consists of two five-membered ruthenacycles [RuBNCS] which are fused by one butterfly moiety [RuB₂S]. Analogous fac-3c, [PPh₃Ru{κ³-H,S,S′-(NH₂BSBH₂N)(SC₅H₄)₂}], can also be synthesized from the reaction of BH₃·THF with [PPh₃{κ²-N,S-(SNC₅H₄)}{κ³-H,S,S′-BH₂(SNH₄C₅)₂}Ru], cis–fac-1c. In stark contrast, when mer-2b was treated with BH₂Mes (Mes = 2,4,6-trimethyl phenyl) it led to the formation of trans- and cis-bis(dihydroborate) complexes [{κ³-S,H,H-(NH₂BMes)Ru(S₂C₇H₄)}₂], (trans-4 and cis-4). Both the complexes have two five-membered [Ru–(H)₂–B–NCS] ruthenacycles with κ²-H–H coordination modes. Density functional theory (DFT) calculations suggest that the activation of boranes across the dual Ru–N site is more facile than the Ru–S one.

Redox-active ruthenium complexes supported by hemilabile κ²-N,S-chelated ruthenacycles undergo unusual dual site B–H bond activation through metal–ligand cooperation with free and bulky boranes.     

Magnesium–halobenzene bonding: mapping the halogen sigma-hole with a Lewis-acidic complex

Complexes of the Lewis base-free cations (^MeBDI)Mg⁺ and (^tBuBDI)Mg⁺ with Ph–X ligands (X = F, Cl, Br, I) have been studied (^MeBDI = HC[C(Me)N-DIPP]₂ and ^tBuBDI = HC[C(tBu)N-DIPP]₂; DIPP = 2,6-diisopropylphenyl). For the smaller β-diketiminate ligand (^MeBDI) only complexes with PhF could be isolated. Heavier Ph–X ligands could not compete with bonding of Mg to the weakly coordinating anion B(C₆F₅)₄⁻. For the cations with the bulkier ^tBuBDI ligand, the full series of halobenzene complexes was structurally characterized. Crystal structures show that the Mg⋯X–Ph angle strongly decreases with the size of X: F 139.1°, Cl 101.4°, Br 97.7°, I 95.1°. This trend, which is supported by DFT calculations, can be explained with the σ-hole which increases from F to I. Charge calculation and Atoms-In-Molecules analyses show that Mg⋯F–Ph bonding originates from electrostatic attraction between Mg²⁺ and the very polar C^δ+–F^δ− bond. For the heavier halobenzenes, polarization of the halogen atom becomes increasingly important (Cl < Br < I). Complexation with Mg leads in all cases to significant Ph–X bond activation and elongation. This unusual coordination of halogenated species to early main group metals is therefore relevant to C–X bond breaking.

Complexes of a highly Lewis acidic Mg cation and the full series of Ph–X (X = F, Cl, Br, I) have been structurally characterized. The Mg⋯X–Ph angle decreases with halogen size on account of the growing halogen σ-hole.     

Green Strategies for the Preparation of Enantiomeric 5–8-Membered Carbocyclic β-Amino Acid Derivatives through CALB-Catalyzed Hydrolysis

Candida antarctica lipase B-catalyzed hydrolysis of carbocyclic 5–8-membered cis β-amino esters was carried out in green organic media, under solvent-free and ball-milling conditions. In accordance with the high enantioselectivity factor (E > 200) observed in organic media, the preparative-scale resolutions of β-amino esters were performed in tBuOMe at 65 °C. The unreacted β-amino ester enantiomers (1R,2S) and product β-amino acid enantiomers (1S,2R) were obtained with modest to excellent enantiomeric excess (ee) values (ee_s > 62% and ee_p > 96%) and in good chemical yields (>25%) in one or two steps. The enantiomers were easily separated by organic solvent/H₂O extraction.     

Bis[pyrrolyl Ru(ii)] triads: a new class of photosensitizers for metal–organic photodynamic therapy

A new family of ten dinuclear Ru(ii) complexes based on the bis[pyrrolyl Ru(ii)] triad scaffold, where two Ru(bpy)₂ centers are separated by a variety of organic linkers, was prepared to evaluate the influence of the organic chromophore on the spectroscopic and in vitro photodynamic therapy (PDT) properties of the compounds. The bis[pyrrolyl Ru(ii)] triads absorbed strongly throughout the visible region, with several members having molar extinction coefficients (ε) ≥ 10⁴ at 600–620 nm and longer. Phosphorescence quantum yields (Φ_p) were generally less than 0.1% and in some cases undetectable. The singlet oxygen quantum yields (Φ_Δ) ranged from 5% to 77% and generally correlated with their photocytotoxicities toward human leukemia (HL-60) cells regardless of the wavelength of light used. Dark cytotoxicities varied ten-fold, with EC₅₀ values in the range of 10–100 μM and phototherapeutic indices (PIs) as large as 5400 and 260 with broadband visible (28 J cm^–2, 7.8 mW cm^–2) and 625 nm red (100 J cm^–2, 42 mW cm^–2) light, respectively. The bis[pyrrolyl Ru(ii)] triad with a pyrenyl linker (5h) was especially potent, with an EC₅₀ value of 1 nM and PI > 27 000 with visible light and subnanomolar activity with 625 nm light (100 J cm^–2, 28 mW cm^–2). The lead compound 5h was also tested in a tumor spheroid assay using the HL60 cell line and exhibited greater photocytotoxicity in this more resistant model (EC₅₀ = 60 nM and PI > 1200 with 625 nm light) despite a lower dark cytotoxicity. The in vitro PDT effects of 5h extended to bacteria, where submicromolar EC₅₀ values and PIs >300 against S. mutans and S. aureus were obtained with visible light. This activity was attenuated with 625 nm red light, but PIs were still near 50. The ligand-localized ³ππ* state contributed by the pyrenyl linker of 5h likely plays a key role in its phototoxic effects toward cancer cells and bacteria.     

A prochelator peptide designed to use heterometallic cooperativity to enhance metal ion affinity

A peptide has been designed so that its chelating affinity for one type of metal ion regulates its affinity for a second, different type of metal ion. The prochelator peptide (PCP), which is a fusion of motifs evocative of calcium loops and zinc fingers, forms a 1 : 2 Zn : peptide complex at pH 7.4 that increases its affinity for Zn²⁺ ∼3-fold in the presence of Tb³⁺ (log β₂ from 13.8 to 14.3), while the 1 : 1 luminescent complex with Tb³⁺ is brighter, longer lived, and 20-fold tighter in the presence of Zn²⁺ (log K from 6.2 to 7.5). This unique example of cooperative, heterometallic allostery in a biologically compatible construct suggests the possibility of designing conditionally active metal-binding agents that could respond to dynamic changes in cellular metal status.