Self-Assembly of Dithiolene-based Coordination Polymers of Mercury(II): Dithioether versus Thiocarbonyl Bonding

The reactions of 4,5-bis(methylthio)-1,3-dithiole-2-thione (L) with mercury(II) halides allowed the isolation and structural characterization of three novel coordination polymers, [HgX₂L]_n (X = I, 1; X = Br, 2; X = Cl, 3). In all cases, the complexation of L on HgX₂ occurs via the thiocarbonyl function. The strength of this Hg–S bond decreases from X = I to X = Cl, as indicated by the increasing Hg–S bond distances (2.583(4) 1; 2.668(4) 2; 2.815(5) ? 3). The 1D polymeric structures result from bridging halide interactions and a combination of π–π and S···S interactions between the sulfur rich ligands. The coordination around the Hg center is distorted tetrahedral in 1, whereas the geometry around the mercury in 3 is better described as distorted square pyramidal. In addition, weak interchain interactions are observed in the crystalline state. The preference of HgI₂ for thiocarbonyl bonding instead of a chelating dithioether bonding was also studied by means of ab initio calculations.     

Selenocysteine versus cysteine reactivity: a theoretical study of their oxidation by hydrogen peroxide

The cysteine and selenocysteine oxidation by H2O2 in vacuo and in aqueous solution was studied using the integrated molecular orbital + molecular orbital (IMOMO) method combining the quadratic configuration method QCISD(T) and the spin projection of second-order perturbation theory PMP2. It is shown that including in the model system of cysteine (selenocysteine) residue up to 20 atoms has significant consequences upon the calculated reaction energy barrier. On the other hand, it is demonstrated that free cysteine and selenocysteine have very similar reaction energy barriers, 77-79 kJ mol(-1) in aqueous solution. It is thus concluded that the high experimental reaction rate constant reported for the oxidation of the selenocysteine residue in the glutathione peroxidase (GPx) active center is due to an important interaction between selenocysteine and its molecular environment. The sensitivity of the calculated energy barrier to the dielectric constant of the molecular environment observed for both cysteine and selenocysteine as well as the catalytic effect of the NH group emphasized in the case of cysteine supports this hypothesis.     

Mechanism of thiol oxidation by the superoxide radical

In spite of the large quantity of experimental work that deals with the oxidation of thiols by superoxide, the mechanism of this reaction is still controversial. The ab initio molecular orbital calculations reported here predict that the main reaction pathway includes the formation of a three-electron-bonded adduct followed by the elimination of the hydroxide anion, giving the sulfinyl radical as the reaction product. The alternative reaction pathway consisting of hydrogen atom transfer from the thiol to the protonated superoxide radical involves a reaction energy barrier that is significantly higher. The difference between the two reaction energy barriers is clearly beyond the expected computational uncertainty. The systematic scanning of the potential energy surface reveals no other competitive reaction pathways. The present results provide a useful basis for the interpretation of the complex experimental data related to thiol oxidation by superoxide radical in a biological environment.     

1,3‐Dipolar Cycloaddition Reactions of Indan‐1‐one Enamines across Arylnitrile Oxides Leading to Novel Cyclic Isoxazoline Derivatives

Synthesis of a series of cyclic fused‐isoxazolines has been accomplished by regioselective and diastereoselective 1,3‐dipolar cycloaddition of 3‐methylindan‐1‐one enamines ( 1a , 1b , 1c ) and 3‐phenylindan‐1‐one enamines ( 2a , 2b , 2c ) to arylnitrile oxides ( 3d , 3e , 3f , 3g , 3h ). The structure of the cycloadducts was elucidated by ¹H and ¹³C NMR spectroscopy. The proposed regio‐ and stereochemistry of fused‐compounds ( 4 ) and ( 5 ) has also been corroborated by two single‐crystal X‐ray diffraction studies carried out on 4‐methyl‐8b‐morpholinyl‐3‐(p‐tolyl)‐4H‐3a,8b‐dihydroindeno[2,3‐d]isoxazoline ( 4be ) and 3‐(p‐anisyl)‐4‐phenyl‐8b‐pyrrolidinyl‐4H‐3a,8b‐dihydroindeno[2,3‐d]isoxazoline ( 5af ) and by means of density functional theory calculations.     

Excited-State Dynamics of Fully Reduced Flavins and Flavoenzymes Studied at Subpicosecond Time Resolution

The photophysics of the fully reduced states of a number of flavins (flavin mononucleotide, flavin adenine dinucleotide and 3-N-methyllumiflavin) and flavoenzymes (glucose oxidase from Aspergillus niger and the flavodehydrogenase component isolated from flavocytochrome b₂) was studied using subpicosecond laser excitation at Λ. = 312 nm. The prompt transient absorption spectra (measured from 400 to 850 nm) were all closely similar in the case of the free flavins in aqueous solution. The decay of the transient absorbance obeyed biexponential kinetics with a fast component of lifetime ranging from 4 to 130 ps and a slower phase with a lifetime above 1 ns. The spectral structure changed appreciably during the rapid decay phase. In contrast, in the case of the enzymes only a very slight decay was apparent over the probed time interval (1 ns) and the shape of the spectrum remained unchanged. It is proposed that the two transient spectra appearing in the free flavins correspond to two conformations differing by their degree of nonplanarity, whereas in the flavoenzymes only one conformation is possible.     

Self-Assembly of Dithiolene-based Coordination Polymers of Mercury(II): Dithioether versus Thiocarbonyl Bonding

Summary. The reactions of 4,5-bis(methylthio)-1,3-dithiole-2-thione (L) with mercury(II) halides allowed the isolation and structural characterization of three novel coordination polymers, [HgX₂L]_n (X = I, 1; X = Br, 2; X = Cl, 3). In all cases, the complexation of L on HgX₂ occurs via the thiocarbonyl function. The strength of this Hg–S bond decreases from X = I to X = Cl, as indicated by the increasing Hg–S bond distances (2.583(4) 1; 2.668(4) 2; 2.815(5) ? 3). The 1D polymeric structures result from bridging halide interactions and a combination of π–π and S···S interactions between the sulfur rich ligands. The coordination around the Hg center is distorted tetrahedral in 1, whereas the geometry around the mercury in 3 is better described as distorted square pyramidal. In addition, weak interchain interactions are observed in the crystalline state. The preference of HgI₂ for thiocarbonyl bonding instead of a chelating dithioether bonding was also studied by means of ab initio calculations.     

A computational study of thiolate and selenolate oxidation by hydrogen peroxide.

Ab initio molecular orbital calculations have been used to study the effects of the molecular environment on the oxidation of thiolate and selenolate by hydrogen peroxide. The reaction was first examined in vacuo at the QCISD(T)/6-311+G(2df,2pd)//MP2/6-311+G(d,p) level of theory. It was found for both thiolate and selenolate that a reactant aggregate is formed, which has a dissociation rate constant comparable to the activation rate constant (about 10(-3) s(-1) for thiolate and 10(-1) s(-1) for selenolate). Using the polarizable continuum model (PCM) it was then found that the dissociation barrier energy decreases dramatically in water giving a dissociation rate constant of the order of 10(9) s(-1). In this case, the predicted overall rate constant of the thiolate reaction was about 10.2 mol(-1) dm3 s(-1), which is in good agreement with the experimental rate constant of cysteine oxidation in aqueous solution. The calculated rate constant for the selenolate reaction was somewhat higher (about 35.4 mol(-1) dm3 s(-1)). However, this value is several orders of magnitude smaller than the experimental value reported for the oxidation of selenocysteine in glutathione peroxidase. By considering the effect of the PCM dielectric constant on the reaction rate constant it was concluded that the high reactivity of the selenocysteine in glutathione peroxidase, as compared with cysteine, could be mainly due to the molecular environment of the selenocysteine residue.     

Mechanism of cysteine oxidation by a hydroxyl radical: a theoretical study.

Cysteine oxidation by HO(.) was studied at a high level of ab initio theory in both gas phase and aqueous solution. Potential energy surface scans in the gas phase performed for the model system methanethiol+HO(.) indicate that the reactants can form two intermediate states: a sulfur-oxygen adduct and a hydrogen bound reactant complex. However these states appear to play a minor role in the reaction mechanism as long as they are fast dissociating states. Thus the main reaction channel predicted at the QCISD(T)/6-311+G(2df,2pd) level of theory is the direct hydrogen atom abstraction. The reaction mechanism is not perturbed by solvation which was found to induce only small variations in the Gibbs free energy of different reactant configurations. The larger size reactant system cysteine+HO* was treated by the integrated molecular orbital+molecular orbital (IMOMO) hybrid method mixing the QCISD(T)/6-311+G(2df,2pd) and the UMP2/6-311+G(d,p) levels of theory. The calculated potential energy, enthalpy, and Gibbs free energy barriers are slightly different from those of methanethiol. The method gave a rate constant for cysteine oxidation in aqueous solution, k=2.4 x 10(9) mol(-1) dm(3) s(-1), which is in good agreement with the experimental rate constant. Further analysis showed that the reaction is not very sensitive to hydrogen bonding and electrical polarity of the molecular environment.     

Oxidation of zinc-thiolate complexes of biological interest by hydrogen peroxide: a theoretical study

Zinc-thiolate complexes play a major structural and functional role in the living cell. Their stability is directly related to the thiolate reactivity toward reactive oxygen species naturally present in the cell. Oxidation of some zinc-thiolate complexes has a functional role, as is the case of zinc finger redox switches. Herein, we report a theoretical investigation on the oxidation of thiolate by hydrogen peroxide in zinc finger cores of CCCC, CCHC, and CCHH kinds containing either cysteine or histidine residues. In the case of the CCCC core, the calculated energy barrier for the oxidation to sulfenate of the complexed thiolate was found to be 16.0 kcal mol(-1), which is 2 kcal mol(-1) higher than that for the free thiolate. The energy barrier increases to 19.3 and 22.2 kcal mol(-1) for the monoprotonated and diprotonated CCCC cores, respectively. Substitution of cysteine by histidine also induces an increase in the magnitude of the reaction energy barrier: It becomes 20.0 and 20.9 kcal mol(-1) for the CCCH and CCHH cores, respectively. It is concluded that the energy barrier for the oxidation of zinc fingers is strictly dependent on the type of ligands coordinated to zinc and on the protonation state of the complex. These changes in the thiolate reactivity can be explained by the lowering of the nucleophilicity of complexed sulfur and by the internal reorganization of the complex (changes in the metal-ligand distances) upon oxidation. The next reaction steps subsequent to sulfenate formation are also considered. The oxidized thiolate (sulfenate) is predicted to dissociate very fast: For all complexes, the calculated dissociation energy barrier is lower than 3 kcal mol(-1). It is also shown that the dissociated sulfenic acid can interact with a free thiolate to form a sulfur-sulfur (SS) bridge in a reaction that is predicted to be quasi-diffusion limited. The interesting biological consequences of the modulation of thiolate reactivity by the chemical composition of the zinc finger cores are discussed.     

PHOTOPHYSICS OF METHYLENE BLUE-POLYNUCLEOTIDE COMPLEXES IN THE PICOSECOND TIME RANGE: INFLUENCE OF THE LOCAL STRUCTURE OF THE POLYNUCLEOTIDE

Abstract—
The photophysics of methylene blue (MB) complexed with 2'-deoxycytidylyl-2'-deoxygua-nosine, polydeoxyguanylic-deoxycytidylic acid, polydeoxyguanylic-polydeoxycytidylic acid and poly-guanylic acid, respectively, was investigated by transient absorption spectroscopy with a time resolution of ˜1 ps. The decays of the transient difference spectra indicate that the radiationless process responsible for the strong shortening of the S, state lifetime of MB associated with a guanine in the polynucleotide chain is similar to that already observed in the case of the MB—guanosine-5'-monophosphate complex, that is, the excited state decays by return of molecules to the ground state without formation of a detectable intermediate state. The local structure of the polynucleotide apparently does not change the nature of the deactivation process but influences significantly the deactivation rate. Thus, the intercalation of MB between guanosine and cytosine increases this rate constant (as compared to that of the MB—guanosine-5'-monophosphate complex) while the interaction of MB intercalated with a supplementary guanine has an opposite effect. The results are discussed in connection with the photosensitizing effect of MB in nucleic acid damage.