Biomedical subjects

O A Raevsky

Publications and source records attributed to O A Raevsky.

6 recordsLinked to original sources

PubMed2006

Physicochemical properties/descriptors governing the solubility and partitioning of chemicals in water-solvent-gas systems. Part 1. Partitioning between octanol and air.

QSPR analyses of a data set containing experimental partition coefficients in the three systems octanol-water, water-gas, and octanol-gas for 98 chemicals have shown that it is possible to calculate any partition coefficient in the system 'gas phase/octanol/water' by three different approaches: (1) from experimental partition coefficients obtained in the corresponding two other subsystems. However, in many cases these data may not be available. Therefore, a solution may be approached (2), a traditional QSPR analysis based on e.g. HYBOT descriptors (hydrogen bond acceptor and donor factors, SigmaCa and SigmaCd, together with polarisability alpha, a steric bulk effect descriptor) and supplemented with substructural indicator variables. (3) A very promising approach which is a combination of the similarity concept and QSPR based on HYBOT descriptors. In this approach observed partition coefficients of structurally nearest neighbours of a compound-of-interest are used. In addition, contributions arising from differences in alpha, SigmaCa, and SigmaCd values between the compound-of-interest and its nearest neighbour(s), respectively, are considered. In this investigation highly significant relationships were obtained by approaches (1) and (3) for the octanol/gas phase partition coefficient (log Log).

1-Octanol↗

PubMed2005

Quantifying hydrogen bonding in QSAR and molecular modeling.

Quantitative descriptions of hydrogen bonding for use in QSAR and molecular modeling by means of H-bond descriptors have been analyzed in detail in this paper. Ten new H-bond surface and enthalpy integral descriptors were proposed. The usefulness of these new descriptors, as well as previously developed descriptors was verified using a set of 154 drugs for which data for intestinal absorption in humans were available. The results showed that descriptors such as the number of H-bond acceptor and donor atoms and polar surface area (PSA) did not sufficiently describe the actual H-bonding ability of atoms in molecules. Thus, to enable successful modeling it was necessary to introduce descriptors directly related to the experimental thermodynamics of hydrogen bonding.

Humans↗

PubMed2001

Molecular lipophilicity calculations of chemically heterogeneous chemicals and drugs on the basis of structural similarity and physicochemical parameters.

QSARs based on molecular polarizability (alpha) and H-bond acceptor factors (sigma Ca) as independent variables provided good predictability of octanol/water partition coefficients (P) for chemicals and drugs. However, for some molecules containing few functional groups, the calculated values deviated significantly from those observed. This approach gave good results when applied to a set of 138 chemicals and drugs previously studied by Mannhold and Dross who compared other methods to calculate log P values. At the same time, three variations on a molecular similarity approach were pursued. In this study, a large training set with experimentally determined octanol/water partition coefficients (P) was searched for structures closely related to the compound-of-interest. The most successful of these variations took the mean log P value of few most closely related compounds after each was adjusted for differences between their and the compound-of-interest's polarizabilities (alpha) and H-bond acceptor capacities (sigma Ca).

Forecasting↗

PubMed1998

Estimation of blood-brain barrier crossing of drugs using molecular size and shape, and H-bonding descriptors.

The influence of physicochemical properties, including lipophilicity, H-bonding capacity and molecular size and shape descriptors on brain uptake has been investigated using a selection of marketed CNS and CNS-inactive drugs. It is demonstrated that the polar surface area of a drug can be used as a suitable descriptor for the drugs' H-bonding potential. A combination of a H-bonding and a molecular size descriptor, i.e., the major components of lipophilicity and permeability, avoiding knowledge of distribution coefficients, is proposed to estimate brain penetration potential of new drug candidates. Previously reported experimental surface activity data appear to be strongly correlated to molecular size of the drug compounds. Present analysis offers a modern basis for property-based design and targeting of CNS drugs.

Blood-Brain Barrier↗

PubMedDate not supplied

Estimating the water solubilities of crystalline compounds from their chemical structures alone.

Partial atomic charges are significant descriptors in predicting the water solubilities of crystalline organic compounds from their chemical structures. Lipophilicity remains the predominant factor. It was also found that quantitative estimates of hydrogen bond strengths (hydrogen bond factors) play important roles. These descriptors can be easily interpreted to guide chemists to the synthesis of compounds with increased or decreased water solubility. This work is based on a set of 22 compounds the aqueous solubilities of which were determined by a new potentiometric method, pSOL, and were confirmed, in part, by the traditional shake-flask method. A new software package, HYBOTPLUS, furnished the partial atomic charges and hydrogen bond factors.

Journal Article↗

PubMedDate not supplied

Creation of predictive models of aquatic toxicity of environmental pollutants with different mechanisms of action on the basis of molecular similarity and HYBOT descriptors.

Over half of known industrial pollutants have minimal toxic effect, in line with the concept of "baseline toxicity"; such toxicity usually correlates well with lipophilicity. The remainder require additional descriptors in order to model their toxicity by the QSAR approach. Hence, it has not been possible, to date, to develop common stable QSAR models for the toxicity of diverse chemicals with various modes of action on the basis of simple regression relationships. Any new methodology has to take such different modes of action into account. In our work, we used for this purpose an original combination of the similarity concept and physicochemical descriptors calculated by HYBOT, in order to construct stable QSAR models of guppy toxicity. The training set comprised 293 diverse chemicals. Experimental value(s) of one or more nearest related chemicals were used to take structural features and possible modes of toxic action into account. In addition, molecular polarisability and hydrogen bond descriptors for the chemicals of interest and related compounds were used to calculate any additional contribution in toxicity by means of linear regression relationships. Final comparison of calculated and experimental toxicity values gave good results, with standard deviation close to the experimental error.

Animals↗