Photoswitchable Sol–Gel Transitions and Catalysis Mediated by Polymer Networks with Coumarin-Decorated Cu24L24 Metal–Organic Cages as Junctions

Photoresponsive materials that change in response to light have been studied for a range of applications. These materials are often metastable during irradiation, returning to their pre-irradiated state after removal of the light source. Herein, we report a polymer gel comprising poly(ethylene glycol) star polymers linked by Cu₂₄L₂₄ metal–organic cages/polyhedra (MOCs) with coumarin ligands. In the presence of UV light, a photosensitizer, and a hydrogen donor, this “polyMOC” material can be reversibly switched between Cu^II, Cu^I, and Cu⁰. The instability of the MOC junctions in the Cu^I and Cu⁰ states leads to network disassembly, forming Cu^I/Cu⁰ solutions, respectively, that are stable until re-oxidation to Cu^II and supramolecular gelation. This reversible disassembly of the polyMOC network can occur in the presence of a fixed covalent second network generated in situ by copper-catalyzed azide-alkyne cycloaddition (CuAAC), providing interpenetrating supramolecular and covalent networks.     

Simultaneously multiply-configurable or superposed molecular logic systems composed of ICT (internal charge transfer) chromophores and fluorophores integrated with one- or two-ion receptors

Integrated "ICT chromophore-receptor" systems show ion-induced shifts in their electronic absorption spectra. The wavelength of observation can be used to reversibly configure the system to any of the four logic operations permissible with a single input (YES, NOT, PASS 1, PASS 0), under conditions of ion input and transmittance output. We demonstrate these with dyes integrated into Tsien's calcium receptor, 1-2. Applying multiple ion inputs to 1-2 also allows us to perform two- or three-input OR or NOR operations. The weak fluorescence output of 1 also shows YES or NOT logic depending on how it is configured by excitation and emission wavelengths. Integrated "receptor(1)-ICT chromophore-receptor(2)" systems 3-5 selectively target two ions into the receptor terminals. The ion-induced transmittance output of 3-5 can also be configured via wavelength to illustrate several logic types including, most importantly, XOR. The opposite effects of the two ions on the energy of the chromophore excited state is responsible for this behaviour. INHIBIT and REVERSE IMPLICATION are two of the other logic types seen here. Integration of XOR logic with a preceding OR operation can be arranged by using three ion inputs. The fluorescence output of these systems can be configured via wavelength to display INHIBIT or NOR logic under two-input conditions. The superposition or multiplicity of logic gate configurations is an unusual consequence of the ability to simultaneously observe multiple wavelengths.     

Evidence for a monomeric structure of nonribosomal Peptide synthetases

Nonribosomal peptide synthetases (NRPS) are multimodular biocatalysts that bacteria and fungi use to assemble many complex peptides with broad biological activities. The same modular enzymatic assembly line principles are found in fatty acid synthases (FAS), polyketide synthases (PKS), and most recently in hybrid NRPS/PKS multienzymes. FAS as well as PKS are known to function as homodimeric enzyme complexes, raising the question of whether NRPS may also act as homodimers. To test this hypothesis, biophysical methods (size exclusion chromatography, analytical equilibrium ultracentrifugation, and chemical crosslinking) and biochemical methods (two-affinity-tag-system and complementation studies with enzymes being inactivated in different catalytic domains) were applied to NRPS subunits from the gramicidin S (GrsA-ATE), tyrocidine (TycB(1)-CAT and TycB(2-3)-AT.CATE), and enterobactin (EntF-CATTe) biosynthetic systems. These methods had revealed the dimeric structure of FAS and PKS previously, but all three NRPS systems investigated are functionally active as monomers.     

Nannocystin A: an Elongation Factor 1 Inhibitor from Myxobacteria with Differential Anti‐Cancer Properties

Cultivation of myxobacteria of the Nannocystis genus led to the isolation and structure elucidation of a class of novel cyclic lactone inhibitors of elongation factor 1. Whole genome sequence analysis and annotation enabled identification of the putative biosynthetic cluster and synthesis process. In biological assays the compounds displayed anti‐fungal and cytotoxic activity. Combined genetic and proteomic approaches identified the eukaryotic translation elongation factor 1α (EF‐1α) as the primary target for this compound class. Nannocystin A ( 1 ) displayed differential activity across various cancer cell lines and EEF1A1 expression levels appear to be the main differentiating factor. Biochemical and genetic evidence support an overlapping binding site of 1 with the anti‐cancer compound didemnin B on EF‐1α. This myxobacterial chemotype thus offers an interesting starting point for further investigations of the potential of therapeutics targeting elongation factor 1.     

Selective anion binding by a cofacial binuclear zinc complex of a Schiff-base pyrrole macrocycle

The synthesis of the new cofacial binuclear zinc complex [Zn(2)(L)] of a Schiff-base pyrrole macrocycle is reported. It was discovered that the binuclear microenvironment between the two metals of [Zn(2)(L)] is suited for the encapsulation of anions, leading to the formation of [K(THF)(6)][Zn(2)(μ-Cl)(L)]·2THF and [Bu(n)(4)N][Zn(2)(μ-OH)(L)] which were characterized by X-ray crystallography. Unusually obtuse Zn-X-Zn angles (X = Cl: 150.54(9)° and OH: 157.4(3)°) illustrate the weak character of these interactions and the importance of the cleft preorganization to stabilize the host. In the absence of added anion, aggregation of [Zn(2)(L)] was inferred and investigated by successive dilutions and by the addition of coordinating solvents to [Zn(2)(L)] solutions using NMR spectroscopy as well as isothermal microcalorimetry (ITC). On anion addition, evidence for deaggregation of [Zn(2)(L)], combined with the formation of the 1:1 host-guest complex, was observed by NMR spectroscopy and ITC titrations. Furthermore, [Zn(2)(L)] binds to Cl(-) selectively in THF as deduced from the ITC analyses, while other halides induce only deaggregation. These conclusions were reinforced by density functional theory (DFT) calculations, which indicated that the binding energies of OH(-) and Cl(-) were significantly greater than for the other halides.     

Iridium-catalyzed hydrogenation of N-heterocyclic compounds under mild conditions by an outer-sphere pathway

A new homogeneous iridium catalyst gives hydrogenation of quinolines under unprecedentedly mild conditions-as low as 1 atm of H(2) and 25 °C. We report air- and moisture-stable iridium(I) NHC catalyst precursors that are active for reduction of a wide variety of quinolines having functionalities at the 2-, 6-, and 8- positions. A combined experimental and theoretical study has elucidated the mechanism of this reaction. DFT studies on a model Ir complex show that a conventional inner-sphere mechanism is disfavored relative to an unusual stepwise outer-sphere mechanism involving sequential proton and hydride transfer. All intermediates in this proposed mechanism have been isolated or spectroscopically characterized, including two new iridium(III) hydrides and a notable cationic iridium(III) dihydrogen dihydride complex. DFT calculations on full systems establish the coordination geometry of these iridium hydrides, while stoichiometric and catalytic experiments with the isolated complexes provide evidence for the mechanistic proposal. The proposed mechanism explains why the catalytic reaction is slower for unhindered substrates and why small changes in the ligand set drastically alter catalyst activity.     

Recent progress in SERS biosensing

This perspective gives an overview of recent developments in surface-enhanced Raman scattering (SERS) for biosensing. We focus this review on SERS papers published in the last 10 years and to specific applications of detecting biological analytes. Both intrinsic and extrinsic SERS biosensing schemes have been employed to detect and identify small molecules, nucleic acids, lipids, peptides, and proteins, as well as for in vivo and cellular sensing. Current SERS substrate technologies along with a series of advancements in surface chemistry, sample preparation, intrinsic/extrinsic signal transduction schemes, and tip-enhanced Raman spectroscopy are discussed. The progress covered herein shows great promise for widespread adoption of SERS biosensing.     

Insertion, isomerization, and cascade reactivity of the tethered silylalkyl uranium metallocene (η(5)-C5Me4SiMe2CH2-κC)2U

Investigation of the insertion reactivity of the tethered silylalkyl complex (η(5)-C(5)Me(4)SiMe(2)CH(2)-κC)(2)U (1) has led to a series of new reactions for U-C bonds. Elemental sulfur reacts with 1 by inserting two sulfur atoms into each of the U-C bonds to form the bis(tethered alkyl disulfide) complex (η(5):η(2)-C(5)Me(4)SiMe(2)CH(2)S(2))(2)U (2). The bulky substrate N,N'-diisopropylcarbodiimide, (i)PrN═C═N(i)Pr, inserts into only one of the U-C bonds of 1 to produce the mixed-tether complex (η(5)-C(5)Me(4)SiMe(2)CH(2)-κC)U[η(5)-C(5)Me(4)SiMe(2)CH(2)C((i)PrN)(2)-κ(2)N,N'] (3). Carbon monoxide did not exclusively undergo a simple insertion into the U-C bond of 3 but instead formed {μ-[η(5)-C(5)Me(4)SiMe(2)CH(2)C(═N(i)Pr)O-κ(2)O,N]U[OC(C(5)Me(4)SiMe(2)CH(2))CN((i)Pr)-κ(2)O,N](2) (4) in a cascade of reactions that formally includes U-C bond cleavage, C-N bond cleavage of the amidinate ligand, alkyl or silyl migration, U-O, C-C, and C-N bond formations, and CO insertion. The reaction of 3 with isoelectronic tert-butyl isocyanide led to insertion of the substrate into the U-C bond, but with a rearrangement of the amidinate ligand binding mode from κ(2) to κ(1) to form [η(5):η(2)-C(5)Me(4)SiMe(2)CH(2)C(═N(t)Bu)]U[η(5)-C(5)Me(4)SiMe(2)CH(2)C(═N(i)Pr)N((i)Pr)-κN] (5). The product of double insertion of (t)BuN≡C into the U-C bonds of 1, namely [η(5):η(2)-C(5)Me(4)SiMe(2)CH(2)C(═N(t)Bu)](2)U (6), was found to undergo an unusual thermal rearrangement that formally involves C-H bond activation, C-C bond cleavage, and C-C bond coupling to form the first formimidoyl actinide complex, [η(5):η(5):η(3)-(t)BuNC(CH(2)SiMe(2)C(5)Me(4))(CHSiMe(2)C(5)Me(4))]U(η(2)-HC═N(t)Bu) (7).     

Basal and squamous cell carcinoma risks for golfers: an assessment of the influence of tee time for latitudes in the Northern and Southern hemispheres

This study investigates the influence of tee time to determine the relative basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) risk for weekly single round competition golfers located in the Northern and Southern latitude ranges between 25°, 35°, 45° and 55°. A comparative risk methodology, employing annual erythemally effective ultraviolet (UVE) exposure calculations was used to determine BCC and SCC risk factors for golfers using a regular weekly tee time. Relative risk was found to be proportional to golf tee time with mid morning tee times generally presenting the greatest risk in each latitude range. The greatest contribution toward the risk of developing basal and squamous cell carcinoma was found to occur for golfers beginning weekly rounds mid to late morning, with specific risk factors of 1.47 (BCC) and 1.98 (SCC) in the Northern hemisphere compared with similar maximum risk factors of 1.51 (BCC) and 2.08 (SCC) in the Southern hemisphere occurring at comparable morning tee times. Differences in annual UVE exposure between the golfer and non-golfer were the largest determinant of BCC and SCC risk. Generally, these risks were found to decrease with lower latitude although contribution toward overall risk was influenced strongly by the global time zone of each studied golf course site.     

A sulfone-based strategy for the preparation of 2,4-disubstituted furan derivatives

2,4-Disubstituted furans are prepared by treating 2,3-dibromo-1-phenylsulfonyl-1-propene (DBP, 2) with 1,3-diketones under basic conditions. The furan-forming step involves a deacetylation, and the selectivity of this process depends upon the steric demand of the R group. The substituent in position 4 is elaborated by reaction of sulfonyl carbanions with alkyl halides, acyl halides, and aldehydes. Oxidative or reductive desulfonylation produces the 2,4-disubstituted furans in 60-92% yield. This strategy has been used to prepare rabdoketone A (12) and the naturally occurring nematotoxic furoic acid 13.