Vancomycin resistance: Modeling backbone variants with d-Ala-d-Ala and d-Ala-d-Lac peptides

To seek vancomycin analogs with broader antibacterial activity, effects of backbone modifications for the agylcon 2 on binding with d-Ala-d-Ala- and d-Ala-d-Lac-containing peptides were investigated by Monte Carlo/free energy perturbation (MC/FEP) calculations. The experimental trend in binding affinities for 2 with three tripeptides was well reproduced. Possible modifications of the peptide bond between residues 4 and 5 were then considered, specifically for conversion of the OCNH linkage to CH₂NH₂⁺ (6), FCCH (7), HCCH (8), and HNCO (9). The MC/FEP results did not yield binding improvements for 7, 8, and 9, though the fluorovinyl replacement is relatively benign. The previously reported analog 6 remains as the only variant that exhibits improved affinity for the d-Ala-d-Lac sequence and acceptable affinity for the d-Ala-d-Ala sequence.     

Organogold(I) complexes of a C2-symmetric diacetylide ligand derived from 1,1′-bi-2-naphthol

Alkynylgold(I) complexes incorporating a chiral binaphthyl group have been prepared. Bis(alkyne) reagents [rac-1,1′-C₂₀H₁₂-2,2′-(OCH₂CCH)₂] (1) and [rac-1,1′-C₂₀H₁₂-2,2′-(OC(O)CH₂CCH)₂] (2), react with [AuCl(SMe₂)] and base to give insoluble oligomeric alkynylgold(I) complexes [rac-1,1′-C₂₀H₁₂-2,2′-(OCH₂CCAu)₂]_n (3) and [rac-1,1′-C₂₀H₁₂-2,2′-(OC(O)CH₂CCAu)₂]_n (4), which react with phosphine or diphosphine ligands to give soluble complexes [rac-1,1′-C₂₀H₁₂-2,2′-(OCH₂CCAuPR₃)₂] (5), R = Ph or Cy, [rac-1,1′-C₂₀H₁₂-2,2′-(OCH₂CCAu)₂(Ph₂P(CH₂)_nPPh₂)] (6), or [rac-1,1′-C₂₀H₁₂-2,2′-(OC(O)CH₂CCAu)₂(Ph₂P(CH₂)_nPPh₂)] (7), with n = 3–5. Several of the complexes 6 and 7 are shown to exist as mixtures of isomeric forms in solution.     

Selective protein modification by the hydroperoxide intermediate in a photoprotein,aequorin

During the course of protein modification program, we employed a recombinant aequorin, the apo-protein reconstituted with coelenterazine, and found out that the photolytic hyperperoxide modified three –S–SCH₂CHOHCHOHCH₂SH groups to –S–SCH₂CHOHCHCH–SO)H or –S–SCH₂CHOHCHCH–S(O)OH of terminal DTT connected to cysteine residues of the C¹⁴⁵, C¹⁵² and C¹⁸⁰, which turned out to locate near the chromophore.     

Novel rhodium complexes containing a bulky iminophosphine ligand and their use as catalysts for the hydroboration of vinylarenes

Addition of o-Ph₂PC₆H₄CHN-2,6-ⁱPr₂C₆H₃ (1) to [RhCl(coe)₂]₂ (coe = cis-cycloctene) gave several new iminophosphino rhodium(I) complexes including [Rh(κ²-o-Ph₂PC₆H₄CHN-2,6-ⁱPr₂C₆H₃)(μ-Cl)]₂ (2). Addition of 1 to Rh(acac)(coe)₂ (acac = acetylacetonato) gave [Rh(acac)(κ²-o-Ph₂PC₆H₄CHN-2,6-ⁱPr₂C₆H₃)] (3) in yields of up to 75%. Complex 3 has been examined for its ability to catalyze the hydroboration of a series of vinyl arenes. Reactions using catecholborane and pinacolborane seem to proceed largely through a dehydrogenative borylation mechanism to give a number of boronated products.     

Synthesis and structure of an unusual di-rhodium diarylbutadiyne π-complex featuring a μ-(1,2-η2):(3,4-η2)-p-CF3C6H4–CC–CC–C6H4-p-CF3 moiety

Reaction of the salt [Rh(PMe₃)₄]Cl (1) with p-F₃C–C₆H₄–CC–CC–C₆H₄-p-CF₃ (2) in THF gives a mixture of two related neutral π-bound diyne complexes of [Rh(PMe₃)₃Cl], each having two distinct CF₃ resonances of equal intensity in the in situ ¹⁹F{¹H} NMR spectrum. The ratio of the two products can be varied by varying the stoichiometry of the reagents. On the basis of the spectroscopic data and literature precedent, we propose Rh(PMe₃)₃(Cl)((1,2-η²)-p-F₃C–C₆H₄–CC–CC–C₆H₄-p-CF₃) (3a) and [Rh(PMe₃)₃(Cl)]₂(μ-(1,2-η²):(1,2-η²)-p-F₃C–C₆H₄–CC–CC–C₆H₄-p-CF₃) (3b) as the most likely structures of the species in solution. However, upon standing overnight, single crystals of the unusual, dinuclear complex [Rh(PMe₃)₃(Cl)]₂(μ-(1,2-η²):(3,4-η²)-p-F₃C–C₆H₄–CC–CC–C₆H₄-p-CF₃) (4), an isomer of 3b, form reproducibly and in good yield as two different solvates from THF/C₆D₆ solution. The centrosymmetric structure of 4, obtained from single-crystal X-ray diffraction data, displays a transoid orientation of the bridging diarylbutadiyne ligand.     

Synthesis and characterization of two isomers of Os3(CO)10(C5H4N-2-C(H)NR) and the conversion to ortho-metallated HOs3(C5H3N-2-C(H)NR)(CO)9. Part III. X-ray Structure of HOs3(C5H3N-2-C(H)Ni-Pr)(CO)9

Os₃(CO)₁₀(MeCN)₂ reacts at room temperature in MeCN or toluene with R-Pyca2 to yield two isomers of Os₃(CO)₁₀(R-Pyca) that differ in the bonding of the R-Pyca ligand to the Os₃(CO)₁₀ unit. In all cases Os₃(CO)₁₀(R-Pyca(4e)) (isomer A; 4a: R = c-Pr, 4b: R = i-Pr, 4c: R = neo-Pent, 4d: R = t-Bu), containing a chelating 4e donating R-Pyca ligand and three OsS bonds, could be isolated. In the case of R = c-Pr and R = i-Pr Os₃(CO)₁₀(R-Pyca(6e)) (isomer B; 5a: R = c-Pr, 5b: R = i-Pr), in which only two OsS bonds are present and the R-Pyca ligand is bonded as a 6e donating ligand bridging two non-bonded Os atoms, could be isolated as a minor product.At 70 °C Os₃(CO)₁₀(R-Pyca(4e)) (4b and 4d) loses one carbonyl and the pyridine moiety of the R-Pyca ligand is ortho-metallated to form HOs₃(C₅H₃N-2-C(H)NR)(CO)₉ (6b: R = i-Pr and 6d: R = t-Bu). Under the same conditions Os₃(CO)₁₀(i-Pr-Pyca(6e)) (5b) reacts to Os₂(CO)₆(6e)) (7b) containing a bridging 6e donating ligands. The latter two reactions were followed with FT-IR spectroscopy in a high temperature IR cell.The structure of the complexes in solution have been studied by ¹H and ¹C NMR and IR spectroscopy. The stoichiometries of 4a and 5a were determined by FAB-mass spectrometry while an exact mass determination was carried out for 4a.The crystal structure of 6b has been determined. Crystal of 6b are monoclinic, space group P2₁/n, with a = 7.808(2),b = 17.613(3),c = 16.400(8)Å, β = 94.09(3)° and Z = 4. The structure was refined to R = 0.039. The molecule contains a triangular array of osmium atoms [Os(1)Os(2) = 2.898(2)Å, Os(1)Os(3) = 2.886(2)Åand Os(2)O(3) = 2.911(2)Å] and nine terminally bonded carbonyl ligands. The C₅H₃N-2-C(H)N-i-Pr ligand is chelate bonded to Os(2) with the pyridine and imine nitrogens atoms axially and equatorially coordinated respectively [Os(2)N(1) = 2.00(2)Åand Os(2)N(2) = 2.11(2)Å]. The i-Pr-Pyca ligand is ortho-metallated at C(1) and forms a four membered ring containing Os(2), Os(3), C(1) and N(1), the Os(3)C(1) distance being 2.12(2)Å. The hydride, which could not be located unequivocally from a difference Fourier map is proposed to bridge the Os(2)(3) bond on the basis of stereochemical considerations.     

Mechanisms and kinetic profiles of superoxide-stimulated nitrosative processes in cells using a diaminofluorescein probe

In this study, we examined the mechanisms and kinetic profiles of intracellular nitrosative processes using diaminofluorescein (DAF-2) as a target in RAW 264.7 cells. The intracellular formation of the fluorescent, nitrosated product diaminofluorescein triazol (DAFT) from both endogenous and exogenous nitric oxide (NO) was prevented by deoxygenation and by cell membrane-permeable superoxide (O₂⁻) scavengers but not by extracellular bovine Cu,Zn-SOD. In addition, the DAFT formation rate decreased in the presence of cell membrane-permeable Mn porphyrins that are known to scavenge peroxynitrite (ONOO⁻) but was enhanced by HCO₃⁻/CO₂. Together, these results indicate that nitrosative processes in RAW 264.7 cells depend on endogenous intracellular O₂⁻ and are stimulated by ONOO⁻/CO₂-derived radical oxidants. The N₂O₃ scavenger sodium azide (NaN₃) only partially attenuated the DAFT formation rate and only with high NO (>120 nM), suggesting that DAFT formation occurs by nitrosation (azide-susceptible DAFT formation) and predominantly by oxidative nitrosylation (azide-resistant DAFT formation). Interestingly, the DAFT formation rate increased linearly with NO concentrations of up to 120–140 nM but thereafter underwent a sharp transition and became insensitive to NO. This behavior indicates the sudden exhaustion of an endogenous cell substrate that reacts rapidly with NO and induces nitrosative processes, consistent with the involvement of intracellular O₂⁻. On the other hand, intracellular DAFT formation stimulated by a fixed flux of xanthine oxidase-derived extracellular O₂⁻ that also occurs by nitrosation and oxidative nitrosylation increased, peaked, and then decreased with increasing NO, as previously observed. Thus, our findings complementarily show that intra- and extracellular O₂⁻-dependent nitrosative processes occurring by the same chemical mechanisms do not necessarily depend on NO concentration and exhibit different unusual kinetic profiles with NO dynamics, depending on the biological compartment in which NO and O₂⁻ interact.     

Synthesis,crystal structure and biological evaluation of new phosphoramide derivatives as urease inhibitors using docking,QSAR and kinetic studies

In an attempt to achieve a new class of phosphoramide inhibitors with high potency and resistance to the hydrolysis process against urease enzyme, we synthesized a series of bisphosphoramide derivatives (01–43) and characterized them by various spectroscopic techniques. The crystal structures of compounds 22 and 26 were investigated using X-ray crystallography. The inhibitory activities of the compounds were evaluated against the jack bean urease and were compared to monophosphoramide derivatives and other known standard inhibitors. The compounds containing aromatic amines and their substituted derivatives exhibited very high inhibitory activity in the range of IC₅₀ = 3.4–1.91 × 10⁻¹⁰ nM compared with monophosphoramides, thiourea, and acetohydroxamic acid. It was also found that derivatives with PO functional groups have higher anti-urease activity than those with PS functional groups. Kinetics and docking studies were carried out to explore the binding mechanism that showed these compounds follow a mixed-type mechanism and, due to their extended structures, can cover the entire binding pocket of the enzyme, reducing the formation of the enzyme-substrate complex. The quantitative structure-activity relationship (QSAR) analysis also revealed that the interaction between the enzyme and inhibitor is significantly influenced by aromatic rings and PO functional groups. Collectively, the data obtained from experimental and theoretical studies indicated that these compounds can be developed as appropriate candidates for urease inhibitors in this field.     

On the use of fluorescence lifetime imaging and dihydroethidium to detect superoxide in intact animals and ex vivo tissues: A reassessment

Recently, D.J. Hall et al. reported that ethidium (E⁺) is formed as a major product of hydroethidine (HE) or dihydroethidium reaction with superoxide (O₂⁻) in intact animals with low tissue oxygen levels (J. Cereb. Blood Flow Metab. 32:23–32, 2012). The authors concluded that measurement of E⁺ is an indicator of O₂⁻ formation in intact brains of animals. This finding is in stark contrast to previous reports using in vitro systems showing that 2-hydroxyethidium, not ethidium, is formed from the reaction between O₂⁻ and HE. Published in vivo results support the in vitro findings. In this study, we performed additional experiments in which HE oxidation products were monitored under different fluxes of O₂⁻. Results from these experiments further reaffirm our earlier findings (H. Zhao et al., Free Radic. Biol. Med. 34:1359, 2003). We conclude that whether in vitro or in vivo, E⁺ measured by HPLC or by fluorescence lifetime imaging is not a diagnostic marker product for O₂⁻ reaction with HE.     

Endothelial NO and O2− production rates differentially regulate oxidative,nitroxidative, and nitrosative stress in the microcirculation

Endothelial dysfunction causes an imbalance in endothelial NO and O₂⁻ production rates and increased peroxynitrite formation. Peroxynitrite and its decomposition products cause multiple deleterious effects including tyrosine nitration of proteins, superoxide dismutase (SOD) inactivation, and tissue damage. Studies have shown that peroxynitrite formation during endothelial dysfunction is strongly dependent on the NO and O₂⁻ production rates. Previous experimental and modeling studies examining the role of NO and O₂⁻ production imbalance on peroxynitrite formation showed different results in biological and synthetic systems. However, there is a lack of quantitative information about the formation and biological relevance of peroxynitrite under oxidative, nitroxidative, and nitrosative stress conditions in the microcirculation. We developed a computational biotransport model to examine the role of endothelial NO and O₂⁻ production on the complex biochemical NO and O₂⁻ interactions in the microcirculation. We also modeled the effect of variability in SOD expression and activity during oxidative stress. The results showed that peroxynitrite concentration increased with increase in either O₂⁻ to NO or NO to O₂⁻ production rate ratio (Q_O2⁻/Q_NO or Q_NO/Q_O2⁻, respectively). The peroxynitrite concentrations were similar for both production rate ratios, indicating that peroxynitrite-related nitroxidative and nitrosative stresses may be similar in endothelial dysfunction or inducible NO synthase (iNOS)-induced NO production. The endothelial peroxynitrite concentration increased with increase in both Q_O2⁻/Q_NO and Q_NO/Q_O2⁻ ratios at SOD concentrations of 0.1–100 μM. The absence of SOD may not mitigate the extent of peroxynitrite-mediated toxicity, as we predicted an insignificant increase in peroxynitrite levels beyond Q_O2⁻/Q_NO and Q_NO/Q_O2⁻ ratios of 1. The results support the experimental observations of biological systems and show that peroxynitrite formation increases with increase in either NO or O₂⁻ production, and excess NO production from iNOS or from NO donors during oxidative stress conditions does not reduce the extent of peroxynitrite mediated toxicity.     

Kinetic study on ESR signal decay of nitroxyl radicals,potent redox probes for in vivo ESR spectroscopy,caused by reactive oxygen species

The effect of the chemical structure of nitroxyl spin probes on the rate at which ESR signals are lost in the presence of reactive oxygen species (ROS) was examined. When the spin probes were reacted with either hydroxyl radical (OH) or superoxide anion radical (O₂⁻) in the presence of cysteine or NADH, the probes lost ESR signal depending on both their ring structure and substituents. Pyrrolidine nitroxyl probes were relatively resistant to the signal decay caused by O₂⁻ with cysteine/NADH. Signal decay rates for these reactions correlated with reported redox potentials of the nitroxyl/oxoammonium couple of spin probes, suggesting that the signal decay mechanism in both cases involves the oxidation of a nitroxyl group. The apparent rate constants of the reactions between the spin probe and OH and between the spin probe and O₂⁻ in the presence of cysteine were estimated using mannitol and superoxide dismutase (SOD), respectively, as competitive standards. The rate constants for spin probes and OH were in the order of 10⁹ M⁻¹ s⁻¹, much higher than those for the probes and O₂⁻ in the presence of cysteine (10³–10⁴ M⁻¹ s⁻¹). These basic data are useful for the measurement of OH and O₂⁻ in living animals by in vivo ESR spectroscopy.     

Antioxidant and acetylcholinesterase inhibition properties of novel bromophenol derivatives

In this study, series of novel bromophenol derivatives were synthesized and investigated for their antioxidant and AChE inhibition properties. Novel brominated diarylmethanones were obtained from the acylation reactions of benzoic acids with substituted benzenes. One of the bromodiarylmethanone was synthesized from the bromination of diarylmethanone with molecular bromine. All diarylmethanones were converted into their bromophenol derivatives with BBr₃. The antioxidant activities of all synthesized compounds were elucidated by using various bioanalytical assays. Radical scavenging activities of compounds 10–24 were evaluated by means of DPPH and ABTS⁺ scavenging activities. In addition, reducing ability of 10–24 were determined by Fe³⁺, Cu²⁺, and [Fe³⁺-(TPTZ)₂]³ reducing activities. α-Tocopherol, trolox, BHA, and BHT were used as positive antioxidant and radical scavenger molecules. On the other hand, IC₅₀ values were calculated for DPPH, ABTS⁺ scavenging, and AChE inhibition effects of novel compounds. The results obtained from the current studies clearly show that novel bromophenol derivatives 20–24 have considerable antioxidant, antiradical, and AChE inhibition effects.     

An experimental and theoretical study of the electronic spectra of tetraethylammonium [bis(1,3-dithiole-2-thione-4,5-dithiolato)zincate(II)], [NEt4]2[Zn(dmit)2], and tetraethylammonium [bis(1,3-dithiole-2-one-4,5-dithiolato)zincate(II)], [NEt4]2[Zn(dmio)2]

Metal-dmit complexes and related compounds have been the object of intense study in the last decade. Despite such efforts on the study of its structural properties, very few attempts have been made to the spectroscopic study of these metal complexes. Experimental reports of its infrared, Raman and UV–Vis spectra present the main spectroscopic features, however, many details of the electronic structure have still to be fully investigated and inconsistent assignments are found in the literature. This work presents a detailed analysis of the UV–Vis spectra of the zinc-dmit, [Zn(dmit)₂]⁻², and the zinc-dmio complex, [Zn(dmio)₂]⁻². The experimental spectrum was deconvoluted and analysed with several theoretical methodologies including ab initio CI calculations, ab initio TD and zindo semi-empirical methods. The results confirm the multi-configuration nature of several excited states and the calculated results were concordant for several transitions. The results lead to a new assignment of the 457 nm band in the [Zn(dmit)₂]⁻² as π(pS_m) → π*CS band. In the metal-dmio, the sulfur substitution by oxygen results in a larger HOMO–LUMO gap and a change in the nature of the frontier orbitals. As the first transition we found, for the dmit compound, a high-intensity π → π*CS while for the zinc-dmio, a low-intensity π → σ*C–S transition.     

Phenylsulfonyl piperazine bridged [1,3]dioxolo[4,5-g]chromenones as promising antiproliferative and antioxidant agents

Two series of sulfonylpiperazines linked [1,3]dioxolo[4,5-g]chromenones were synthesized featuring phenyl (7a-k) and chalcone (12a-k) bridge representing flavones or homoisoflavonoids core. New molecules are synthesized utilizing aldol condensation to inspect as antioxidants against DPPH and ABTS⁺ and antiproliferative agents toward selected human cancer cell lines. Cytotoxicity of new compounds was confirmed using SRB assay against non-cancer MDCK cell line. The results concluded that both individual structures of 7 and 12 were vital for modulating pharmacological potencies and presence of different electron withdrawing and electron donating functional group(s) on the phenylsulfonyl entity yielded varied biological effects. Substituent h (OCF₃) and j, k (OCH₃) were found to play a crucial role scavenging DPPH and ABTS⁺ as well as inhibiting cancer cell lines SK-OV-3 and HT-29. Moreover, molecules bearing halogen atom(s) such as substituent b-g expressed excellent inhibitory potential against HeLa and A-549 cancerous cell lines. Bioassay data displayed some interesting structure-activity relationships which are discussed in this paper. The results justified that tested derivatives are promising antioxidants and cytotoxic agents and warrant further structural optimization and bioassay studies. Spectroscopic techniques such as FT-IR, ¹H NMR, ¹³C NMR and elemental analysis (CHN) were carried out to confirm the final structures.     

Four- versus five-coordination in platinum(II) complexes of α-diimines and the crystal structure of [PtClMe(i-PrNCHCHNi-Pr)]

The complex [PtCIMe(i-PrNCHCHNi-Pr)] and its unstable five-coordinate ethylene adduct have been prepared and characterized by ¹H NMR. The crystal and molecular structure of the former has been determined. The complex crystallizes in the orthorhombic space group Pca2 ₁, with a = 12.138(6), b = 9.601(6), c = 10.586(6)Å, Z = 4. Refinement converged to a final R index of 0.059. The geometrical parameters of the structure are compared with those of a related complex and discussed in relation to the stability of the five-coordinate olefin adducts.     

Synthesis and coordination of the bifunctionalized ylides Ph2P(CH2)n(Ph)2PCHCOOMe (n = 1, 2) and ketenylidene Ph2P(CH2)2(Ph)2PCCO to Pd and Pt complexes

In this paper it is reported the synthesis of the phosphonium salts [Ph₂P(CH₂)_n(Ph)₂PCH₂COOMe]Br (n = 1 (1), 2 (2)) and [Ph₂P(CH₂COOMe)(CH₂)_n(Ph)₂PCH₂COOMe]Br₂ (n = 3 (3)) derived from the reactions of the diphosphines dppm, dppe and dppp with methyl bromoacetate. By reaction of the monophosphonium salt of dppm and dppe with the strong base Na[N(SiMe₃)₂] the corresponding carbonyl stabilized ylides Ph₂P(CH₂)_n(Ph)₂PCHCOOMe (n = 1 (4), 2 (5)) were obtained. The Ph₂P(CH₂)₂(Ph)₂PCHCOOMe (5) ylide was reacted with Pd(II) and Pt(II) substrates. From these reactions were isolated exclusively complexes in which the ylide was chelated to the metal through the free phosphine group and the ylidic carbon atom. A further reaction of the Ph₂P(CH₂)₂(Ph)₂PCHCOOMe (5) ylide with 1.5 equiv. of Na[N(SiMe₃)₂] gives the bifunctionalized ketenylidene Ph₂P(CH₂)₂(Ph)₂PCCO (6) system. This cumulenic ylide reacts with Pt(II) complexes to form a chelated derivative in which IR and NMR spectra suggest the breaking of the CC bond of the -CCO group.     

Synthesis and characterization of cis-dioxomolybdenum(VI) complexes with sterically bulky tripodal tetradentate ligands

A new series of sterically bulky tripodal tetradentate ligands have been synthesized. The ligands were found to react readily with MoO ₂(acac) ₂ in absolute methanol to yield the corresponding cis- dioxoMo(VI) complexes. These complexes were characterized by IR, ¹H and ¹³C NMR, UV-Vis spectroscopy, elemental analysis and cyclic voltammetry (CV). Cyclic voltammetry was performed in DMF and CH ₂Cl ₂. In CH ₂Cl ₂ the ease of reduction was found to decrease in the order MoO ₂[LNO ₂ (SCH ₃)]> MoO ₂[LNO ₂(OCH ₃)]> MoO ₂ [LNO ₂ (N(CH ₃) ₂)]. The CV results are consistent with that expected for a S,O,N substitution pattern.     

Antioxidant capacities in various animal sera as measured with multiple free-radical scavenging method

Scavenging abilities of animal sera against six reactive species (OH, O₂⁻, RO, t-BuOO, H₃C, and ¹O₂) were determined with the use of multiple free-radical scavenging (MULTIS) method. Commercially available sera from pig, horse, rabbit, Guinea pig, hamster and chicken were subjected to MULTIS analysis and the results were compared with human specimen. In general, animal sera showed lower scavenging ability against OH and RO radicals than human serum. However, it is noteworthy that rabbit and chicken sera have higher scavenging ability against O₂⁻ than others. This is consistent with the known data that superoxide dismutase levels in these sera are high. In addition, we determined the uric acid level in animal sera using the uricase-TOOS method. In chicken serum, uric acid was found to be the major effective component in RO scavenging. This paper is first to quantitatively evaluate antioxidant capacities in animal sera.     

Enhancements of enantio and diastereoselectivities in reduction of (Z)-3-halo-4-phenyl-3-buten-2-one mediated by microorganisms in ionic liquid/water biphasic system

Reductions of (Z)-C₆H₅CHCXC(O)CH₃ (X = Cl, Br) mediated by Saccharomyces cerevisiae, Candida albicans, Rhodotorula glutinis, Geotrichum candidum and Micrococcus luteus gave the corresponding halohydrins through consecutive reduction reactions of CC and CO bonds. In general, the reactions performed in the biphasic system water/[(bmim)PF₆] gave better diastereoselectivity and enantioselectivity than in pure water.     

Kinetics and mechanism of auto- and copper-catalyzed oxidation of 1,4-naphthohydroquinone

Although quinones represent a class of organic compounds that may exert toxic effects both in vitro and in vivo, the molecular mechanisms involved in quinone species toxicity are still largely unknown, especially in the presence of transition metals, which may both induce the transformation of the various quinone species and result in generation of harmful reactive oxygen species. In this study, the oxidation of 1,4-naphthohydroquinone (NH₂Q) in the absence and presence of nanomolar concentrations of Cu(II) in 10 mM NaCl solution over a pH range of 6.5–7.5 has been investigated, with detailed kinetic models developed to describe the predominant mechanisms operative in these systems. In the absence of copper, the apparent oxidation rate of NH₂Q increased with increasing pH and initial NH₂Q concentration, with concomitant oxygen consumption and peroxide generation. The doubly dissociated species, NQ²⁻, has been shown to be the reactive species with regard to the one-electron oxidation by O₂ and comproportionation with the quinone species, both generating the semiquinone radical (NSQ⁻). The oxidation of NSQ⁻ by O₂ is shown to be the most important pathway for superoxide (O₂⁻) generation with a high intrinsic rate constant of 1.0×10⁸ M⁻¹ s⁻¹. Both NSQ⁻ and O₂⁻ served as chain-propagating species in the autoxidation of NH₂Q. Cu(II) is capable of catalyzing the oxidation of NH₂Q in the presence of O₂ with the oxidation also accelerated by increasing the pH. Both the uncharged (NH₂Q⁰) and the mono-anionic (NHQ⁻) species were found to be the kinetically active forms, reducing Cu(II) with an intrinsic rate constant of 4.0×10⁴ and 1.2×10⁷ M⁻¹ s⁻¹, respectively. The presence of O₂ facilitated the catalytic role of Cu(II) by rapidly regenerating Cu(II) via continuous oxidation of Cu(I) and also by efficient removal of NSQ⁻ resulting in the generation of O₂⁻. The half-cell reduction potentials of various redox couples at neutral pH indicated good agreement between thermodynamic and kinetic considerations for various key reactions involved, further validating the proposed mechanisms involved in both the autoxidation and the copper-catalyzed oxidation of NH₂Q in circumneutral pH solutions.