PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Models, Chemical”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 109 records · Page 6Linked to original sources
PubMed1989

Metabolism of metapramine in vitro by chemical model systems and rat liver microsomes.

Metapramine (Timaxel) was oxidised by hepatic microsomes from rat and by biomimetic chemical systems; vanadyl acetylacetonate-iodylbenzene, phthalocyanin-iron II-iodosylbenzene, meso tetraphenyl porphyrine-iron III chloride-iodosylbenzene and Fenton's reagent. The major metabolite in all cases was the monodemethylated product formed by oxydative removal of the methyl group on the endocyclic nitrogen atom.

Animals↗
PubMedDate not supplied

[Anticonvulsive activity of antiepileptic drugs and quantum-chemical modelling of their interaction with GABA(A) receptor].

The results of experimental analysis of the clinical activity of the antiepileptic drugs' (Phenobarbital, Carbamazepine, Valproic acid, Lamotrigine, Topiramate, Felbamate) widely used in clinic, that was carried out using the standard convulsion test with bicuculline in vivo were compared with characteristics of these drugs' interaction with the key aminoacids of GABA(A) receptor calculated by quantum chemical method (program HyperChem7, semi-empirical method AM1 technique). The correlation between the activity of the drugs in the experiment in vivo and energy of system's interaction of the drugs with aminoacid residue Thr201-Thr202-Gly203- Ala204-Tyr205-Pro206 was found out.

Animals↗
PubMed2002

Chemical models for cytochrome P450 as a biomimetic metabolic activation system in mutation assays.

DNA damage is a critical factor in carcinogenesis. The Ames assay is a short-term test that screens for DNA-damaging agents. To be detected in the assay, most carcinogens require oxidation by cytochrome P450, a component of the liver homogenate preparation (S9 mix) that is traditionally used to metabolize promutagens to an active form in vitro. A combination of iron(III) porphyrin plus an oxidant activates many promutagens by mimicking cytochrome P450 metabolism. We previously reported that the mutagenicity of the N-nitrosodialkylamines was detected following reaction with tetrakis(pentafluorophenyl)porphyrinatoiron(III) chloride (Fe(F(5)P)Cl) plus tert-butyl hydroperoxide (t-BuOOH), which yielded the same alcohols and aldehydes as the enzymatic reaction. In the present study, to extend the scope of biomimetic models, we tested the mutagenicity of other carcinogens exposed to chemical oxidation systems.We investigated the optimal assay conditions for the models in Salmonella typhimurium TA1538, a strain sensitive to frame-shift mutagens. We activated 2-aminofluorene (AF), benzo[a]pyrene (B[a]P), a tryptophane pyrolysate 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2), and 2-acetylaminofluorene (AAF) with Fe(F(5)P)Cl plus an oxidant-t-BuOOH, m-chloroperoxybenzoic acid (mCPBA), or magnesium monoperoxyphthalate (MPPT)-and we noted the effect of three solvents-acetonitrile (CH(3)CN),1,4-dioxane, and N,N-dimethylformamide (DMF)-on AF activation. All the promutagens became mutagenic in the presence of Fe(F(5)P)Cl plus an oxidant, with the effectiveness of the oxidant varying with the chemical. Aromatic amines, for example, showed the strongest mutagenicity with t-BuOOH whereas polycyclic hydrocarbons showed the strongest mutagenicity with mCPBA. All the promutagens were mutagenic in the presence of Fe(F(5)P)Cl plus MPPT. For AF activation, the order of effectiveness of the solvents was CH(3)CN>1,4-dioxane>DMF. The results suggested that these systems would serve as useful models for microsomal activating systems.

2-Acetylaminofluorene↗
PubMed2002

A mechano-chemical model for energy transduction in cytochrome c oxidase: the work of a Maxwell's god.

Cytochrome c3 has a central role in the energetics of Desulfovibrio sp., where it performs an electroprotonic energy transduction step. This process uses a network of cooperativities, largely based on anti-Coulomb components, resulting from a mechano-chemical energy coupling mechanism. This mechanism provides a model coherent with the data available for the redox chemistry of haem a of cytochrome c oxidase and its link to the activation of protons. A crucial feature of the model is an anti-Coulomb effect that sets the stage for a molecular ratchet, ensuring vectoriality for the redox-driven localised movement of protons across the membrane, against an electrochemical gradient.

Biophysical Phenomena↗
PubMed2001

On T2-shortening by weakly magnetized particles: the chemical exchange model.

Chemical exchange (CE) theory is compared with two theories of T2-shortening caused by microscopic magnetic centers: inner- and outer-sphere relaxation theory (long-echo limit) and mean gradient diffusion theory (short-echo limit). The CE equation is shown to be identical to these theories in the respective limits and appropriate parameter relationships are derived for spherical particles. The theories are then compared with computer simulations of spherical particles and with a recent general theory, with good agreement in the asymptotic regions. The CE model also reproduces the essential relaxation characteristics in the intermediate range. Finally, good agreement of a CE model with simulations for magnetized cylinders is also demonstrated. The discussion is limited to weakly magnetized particles such that the maximum phase shift during an echo interval is less than one radian, permitting the use of the Luz-Meiboom CE equation. Published 2001 Wiley-Liss, Inc.

Computer Simulation↗
PubMedDate not supplied

Reduction of nitroimidazoles in model chemical and biological systems.

Some chemical and biological properties of intermediates obtained during reduction of nitroimidazoles are discussed. These include: rate data for the decay of the nitro radical-anion, stoichiometry and absorption spectra for reduction via the radical-anion or using dithionite, stoichiometry with other reducing agents, and rate of reduction by xanthine/xanthine oxidase. Increased radiosensitization by misonidazole is seen upon prolonged pre-irradiation incubation using E. coli, enabling demonstration that a freely-diffusable metabolite is responsible for this effect. Preliminary experiments designed to extend studies of the radiobiological properties of extracellularly-added metabolites to mammalian cells and the use of liver perfusion to generate metabolites are described.

Animals↗
PubMed2005

A chemical model for redox regulation of protein tyrosine phosphatase 1B (PTP1B) activity.

Growing evidence indicates that endogenously produced hydrogen peroxide acts as a cellular signaling molecule that (among other things) can regulate the activity of some protein phosphatases. Recent X-ray crystallographic studies revealed an unexpected chemical transformation underlying the redox regulation of protein tyrosine phosphatase 1B, in which oxidative inactivation of the enzyme yields an intrastrand protein cross-link between the catalytic cysteine residue and its neighboring amide nitrogen. This work describes a small organic molecule that serves as an effective model for the redox-sensing assembly of functional groups at the active site of PTP1B. Findings obtained using this model system suggest that the oxidative transformation of PTP1B to its "crosslinked" inactive form can proceed directly via oxidation of the active-site cysteine to a sulfenic acid (RSOH). The remarkably facile nature of this protein cross-link-forming reaction, along with the widespread cellular occurrence of protein sulfenic acids generated via oxidation of cysteine residues, suggests that the type of oxidative protein cross-link formation first seen in the context of PTP1B represents a potentially general mechanism for redox "switching" of protein function. Thus, the chemistry characterized here could have broad relevance to both redox-regulated signal transduction and the toxic effects of oxidative stress.

Models, Chemical↗
PubMed1985

The OR control system of bacteriophage lambda. A physical-chemical model for gene regulation.

A quantitative model has been developed for processes in the bacteriophage lambda that control the switchover from lysogenic to lytic modes of growth. These processes include the interactions of cI repressor and cro proteins at the three DNA sites of the right operator, OR, the binding of RNA polymerase at promoters PR and PRM, the synthesis of cI repressor and cro proteins, and the degradative action of recA during induction of lysis. The model is comprised of two major physical-chemical components: a statistical thermodynamic theory for relative probabilities of the various molecular configurations of the control system; and a kinetic model for the coupling of these probabilities to functional events, including synthesis of regulatory proteins cI and cro. Using independently evaluated interaction constants and rate parameters, the model was found capable of predicting essential physiological characteristics of the system over an extended time. Sufficiency of the model to predict known physiological properties lends credence to the physical-chemical assumptions used in its construction. Several major physiological characteristics were found to arise as "system properties" through the non-linear, time-dependent, feedback-modulated combinations of molecular interactions prescribed by the model. These include: maintenance of the lysogenic state in the absence of recA-mediated cI repressor degradation; induction of lysis and the phenomenon of subinduction; and autogenous negative control of cro. We have used the model to determine the roles, within the composite system, of several key molecular processes previously characterized by studies in vitro. These include: co-operativity in cI repressor binding to DNA; interactions between repressors and RNA polymerase (positive control); and the monomer-dimer association of cI repressor molecules. A major role of cI repressor co-operativity is found to be that of guaranteeing stability of the lysogenic state against minor changes in cI repressor levels within the cell. The role of positive control seems to be that of providing for a peaked, rather than monotonic, dependence of PRM activity on cI repressor level, while permitting PR activity to be a step function. The model correlates an immense body of studies in vivo and in vitro, and it makes testable predictions about molecular phenomena as well as physiological characteristics of bacteriophage lambda. The approach developed in this study can be extended to include more features of the lambda system and to treat other systems of gene regulation.

Allosteric Regulation↗
PubMed1993

Peracid oxidation of an N-hydroxyguanidine compound: a chemical model for the oxidation of N omega-hydroxyl-L-arginine by nitric oxide synthase.

Arginine is oxidized by a class of enzymes called the nitric oxide synthases (NOS) to generate citrulline and, presumably, nitric oxide (.NO). N-Hydroxylation of a guanidinium nitrogen of arginine to generate N-hydroxyarginine (NOHA) has been shown to be a step in the biosynthesis of .NO. In an effort to elucidate the mechanism by which further oxidation of NOHA occurs, the oxidation of a model N-hydroxyguanidine compound by several peracids was studied in depth. This oxidative chemistry is a possible model for the enzymatic process since the corresponding urea (or citrulline equivalent product) is obtained along with an oxidized nitrogen species. The oxidized nitrogen product was, however, not .NO but rather HNO. .NO generation in this chemical system and in the enzymatic process would require another one-electron oxidation. The mechanistic details of this are further discussed.

Amidines↗
PubMed1978

Chemical models for possible nitrosamine artifact formation in environmental analysis.

Preliminary data concerning two different phenomena of potential importance to those studying the analysis and formation of environmental N-nitroso compounds are presented. First of all, we report that inorganic nitrite in the solid phase can serve as an effective nitrosating agent for solutions of amines in certain nonaqueous media. Secondly, we describe evidence suggesting that the appearance of nitrosamines as contaminants in deionized water (Cohen, 1977; Gough et al., 1977; Fiddler et al., 1977) might result at least partly from simple, acid-catalyzed nitrosation of the amine/ammonium functional groups on the anion exchange resins used in the demineralization process. Possible implications of both phenomena are discussed and potentially useful measures for their control are suggested.

Catalysis↗
PubMed1995

Physico-chemical modeling of the role of free radicals in photodynamic therapy. III. Interactions of stable free radicals with excited photosensitizers studied by kinetic ESR spectroscopy.

The loss of paramagnetism of the stable free radical 4,4'-di-tert.-butyl- diphenyl-1-nitroxy during illumination of the photosensitizer meso-tetrahydroxyphenyl chlorine by light above 620 nm in the absence of oxygen has been followed by kinetic ESR spectroscopy. Addition of the spin trap alpha-(4-pyridyl-1-oxide)- N-tert.-butyl-nitrone reduces the initial rate of the disappearance of the free radical enabling to separate triplet-doublet interactions from processes between radicals stemming from the triplet sensitizer and the stable free radical. Kinetic treatment of the mechanism suggested yielded the rate constant of the triplet-doublet interaction proceeding via electron transfer being about 6% of the rate constant of the overall interaction including both energy transfer and electron transfer.

Biphenyl Compounds↗
PubMed1996

Multilayered dermal subcompartments for modeling chemical absorption.

Dermal penetration of chemicals and drugs is of concern to both toxicologists and pharmacologists. Environmental professionals try to limit exposure to chemicals using protective clothing and gloves or barrier creams to trap chemicals. Drug developers try to enhance penetration of chemicals through the skin for medical purposes. Both can use predictive biologically-based mathematical models to assist in understanding the processes involved. These models are especially useful when they are based on physiological and biochemical parameters which can be measured in the laboratory. Appropriately validated models based on conservation of mass, diffusion and chemical transport by flow can be predictive of human exposures. In this paper we develop two new physiologically-based pharmacokinetic (PBPK) skin models to predict blood concentrations of dibromomethane in rats after skin-only vapor exposures. These new models improve the predictions of the blood concentrations especially at the beginning of the exposures. Sensitivity analysis shows that the permeability constants followed by partition coefficients have the most impact on blood concentration predictions. With proper validation the new models could be used to improve species, dose, and duration extrapolations of chemical or drug penetration. They could also be used to investigate and predict concentrations of drugs or chemicals in the skin.

Animals↗