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Y H Mariam

Publications and source records attributed to Y H Mariam.

7 recordsLinked to original sources
PubMed1997

Electron affinities of p-benzoquinone, p-benzoquinone imine and p-benzoquinone diimine, and spin densities of their p-benzosemiquinones computed by several quantum chemical models.

Restricted and unrestricted (U) Hartree-Fock (HF), second-order Møller-Plesset perturbation (MP2), density functional (DF), hybrid HF/DF and semiempirical (half-electron (HE) method) models have been used to calculate adiabatic electron affinities (EAad values) of p-benzoquinone (I), p-benzoquinone imine (VI) and p-benzoquinone diimine (XI), as well as expectation values ( ) and spin density distributions in the radical anions of I, VI and XI. The AM1/AM1-HE and ab initio calculated structures are found to be in accord with each other. The ROHF/6-31G(d) method gave the poorest EAad result. The UHF and UMP2 wave functions were found to be substantially spin contaminated (for the radicals) and the accuracies of the EAad values calculated were also poor. The use of molecular energies obtained after spin annihilation did not lead to significant improvement of the UHF and UMP2 results. In contrast to the ROHF, UHF and UMP2 results, the DF(USVWN, UBVWN, UBLYP) and hybrid HF/DF(UB3LYP) methods, as well as the AM1-HE, gave much better results. The calculated EAad values decreased, as predicted by most of the models, in the order EAad(I) > EAad(VI) > EAad(XI). The differences in the EAs, EAad(I)-EAad(VI) and EAad(I)-EAad(XI), were consistently predicted to be about 8-9 and 17-18 kcal/mol, respectively, by the DF, B3LYP and AM1-HE models. The performance of the PM3 and SAM1 models was not as good as the AM1 model. Of all the methods tested, the B3LYP/6-311G(d,p) model is concluded to give the most accurate quantitative trend (I(42.6) > VI(33.1) > XI(23.7)) in EAad. The predicted trend in EA can satisfactorily be rationalized by the calculated LUMO orbital energies, atomic charges and spin density distributions. Analysis of the spin density data predicts that phenoxyl- and anilino-type radical anions predominate in the p-benzosemiquinones of I and XI, respectively, while both phenoxyl- and anilino-type radicals contribute to the structure of the p-benzosemiquinone of VI, with the anilino-type predominating.

Benzoquinones↗
PubMed1996

A computational study on the relative reactivity of reductively activated 1,4-benzoquinone and its isoelectronic analogs.

The redox capacities of p-benzoquinone (I) and its analogs p-benzoquinone imine (VI) and p-benzoquinone diimine (XI) as the simplest model systems for the biochemically important quinone site of the pharmacophores of the anthracyclines has been investigated by AM1 semi-empirical and ab initio methods. The reductive activation of the parent (Q) model systems to their various redox states (quinone radical anion (Q.-), semiquinone (QH.), semiquinone anion (QH-) and hydroquinone (QH2)), the internal geometrical reorganization and the redox capacities of the redox states have been examined by using energy-partitioning analysis, reaction enthalpies/energies for electron and proton attachments, adiabatic ionization potentials (IPad) and electron affinities (EAad), adiabatic electronegativities (Xad), dipole moments, electrostatic potentials and spin-density surfaces. EAad data and results of energy-partitioning analysis suggest that the one-electron Q to Q.- reducibility of VI is diminished when compared to that of I. The data also predict that reduction to QH., QH- and QH2 is more favorable in VI (cf. I). Deprotonation enthalpy/energy calculations predict that the oxidizability of the reduced forms of VI is diminished when compared to I. Overall, the calculations suggest that the redox cycling of VI should be diminished if deprotonation is the first step of the autoxidation of the reduced forms. The results suggest that the electron affinity of Q and deprotonation of the reduced forms (e.g., QH.) may play important roles in the redox cycling of the anthracyclines. It is further suggested that these same factors are probably responsible for the reduced toxicity of 5-iminodaunomycin, which consists of VI as part of its pharmacophore. A comparison of the AM1 results with ab initio results suggests that the AM1 method is capable of predicting trends in redox capacity, nucleophilicity, electrophilicity and electron affinity in the systems investigated.

Antibiotics, Antineoplastic↗
PubMed1987

A free radical scavenger role for daunomycin: inhibition of nonenzymatic oxidation of NADH.

The effect of daunomycin(Dm) on the nonenzymatic oxidation of NADH in the presence of metal ions, H2O2 and various ligands was examined. The results show that daunomycin inhibits the oxidation of NADH by reacting with one or more of the reaction intermediates which include OH., HO2., O2. and NAD.. This reaction is a reductive one involving the anthraquinone moiety of daunomycin as confirmed by control experiments by comparative UV-Vis analysis of the spectral character of daunomycin after reduction by NaBH4. Daunomycin, once reduced, apparently does not transfer its electron to another species such as O2 and is thus thought to play the role of free radical scavenger.

DNA↗
PubMed1986

Degradation of DNA by metalloanthracyclines: requirement for metal ions.

Metallodaunomycin has been shown to cleave DNA only in the presence of oxygen, a reducing agent and a metal ion under reaction conditions similar to those used for the cuprous-phenanthroline complex. The intermediacy of 02-. and H2O2 has been substantiated by experiments with superoxide dismutase and catalase, respectively. Only partial inhibition by OH. scavengers was observed. An important feature of the reaction is that no specificity for Cu(II) was observed. This observation has led us to propose a reaction mechanism different from that proposed for the cuprous-phenanthroline complex. The mechanism proposed includes a catalytic role for metal ions other than Cu(II) as well as the direct participation of products of metal-catalyzed redox reactions such as semiquinone and/or hydroquinone of daunomycin.

Acetates↗
PubMed1981

Irreversible inactivation of yeast glucose-6-P dehydrogenase by penicillin G.

Yeast glucose-6-P dehydrogenase is irreversibly inactivated by penicillin G. Kinetic data show that 1 molecule of penicillin G reacts with each active unit when the enzyme is inactivated. The rate of inactivation increases greatly with increasing pH. This irreversible inactivation by penicillin G is largely prevented by pyridoxal-P, a reversible inactivator or this enzyme. Prior treatment of penicillin G with penicillinase totally abolishes its ability to inactivate the enzyme.

Dose-Response Relationship, Drug↗
PubMed1977

Solvent effects on thiamin-enzyme model interactions. I. Interactions with tryptophan.

The solvent polarity dependence of the interaction between thiamin and tryptophan was studied by spectrophotometric methods. The ultraviolet (UV) data clearly indicate that the interaction is weakened when the complex is transferred from water to aqueous ethanol or aqueous dioxane. The interaction of thiamin and tryptophan could also be detected by fluorescence-quenching studies (excitation of tryptophan at 287 nm, maximum emission at 348 nm). Appropriate treatment of the quenching data allowed dissection into static and dynamic contributions. A pyrimidine derivative related to thiamin, both in its neutral and protonated states, was shown to interact with tryptophan by fluorescence techniques, but not by UV. A thiazolium model was shown to interact with tryptophan by UV but was an inefficient quencher of the tryptophan fluorescence. Theoretical models are presented to explain the solvent dielectric constant dependence of the association constant between tryptophan and thiamin. Both electrostatic and dispersion forces are found to contribute to the stability of the complex.

Binding Sites↗