Theoretical approach to identify carcinogenic activity of polycyclic aromatic hydrocarbons

Polycyclic aromatic hydrocarbons (PAHs) are a class of planar molecules that can induce chemical carcinogenesis. Their carcinogenic powers vary in a large range, from the very strong carcinogens to the inactive ones. Many models have been proposed to explain the PAHs' carcinogenic activity, but all of them present some failures. Here we introduce a new methodology to identify PAHs' carcinogenic activity based on the concept of electronic local density of states (LDOS). We show that the analysis of the molecular energy levels in association with the LDOS calculated over the ring which contains the highest bond order of the molecule allows simple rules to identify whether a specific PAH molecule will present (or not) carcinogenic activity.7761186118

A semi-empirical study on the electronic structure of ellipticines

Ellipticine and some of its derivatives are organic molecules with intense antitumor activity. In this work we report a semiempirical study on the electronic structure of ellipticine and some derivatives. Geometrical and spectroscopic aspects were investigated through the use of the well-known PM3 (Parametric Method 3) and ZINDO (Zerner's Intermediate Neglect of Differential Overlap) methods. Comparing PM3 and previously reported AM1 (Austin Method One) results, we found out that overall PM3 results are better. The ZINDO simulated absorption spectra compare well to the available experimental data. We have observed a very simple correlation between the dipole moment value (DM) and the antitumor activity. These results suggest a way to improve and design new antitumor ellipticine derivatives, as well as, to select promising molecules from untested groups. (C) 1999 Elsevier Science B.V. All rights reserved.4654170021922

NUMERICAL STUDY OF TRANSPORT IN A DISSIPATIVE MEDIUM

A numerical study of propagation of a particle through a one-dimensional dissipative medium is presented. The medium is composed of several dissipative sections, which are characterized by their friction coefficients eta. In particular, we have considered two types of friction coefficients distributed orderly or disorderly along the chain. For the same relative proportion of the coefficients, we have found that transport can be enhanced in the disordered distribution in comparison with the ordered one. We also show how this can be considered an approximated way to treat the propagation in a dissipative medium with a position-dependent friction coefficient.4563592359

Pattern recognition methods investigation of ellipticines structure-activity relationships

Ellipticine is a molecule derived from the natural extract Ochrosia elliptica. This molecule and its derivatives are highly cytotoxic to malignant cultured cells. The relatively simple structure of ellipticine has prompted chemists to design various structural modifications in order to obtain either more active derivatives or information on the structural moieties required for pharmacological activities. In the present work we report theoretical structure-activity relationship studies for 40 ellipticine derivatives using pattern-recognition methods such as electronics indices methodology (EIM), principal component analysis (PCA) and hierarchical clustering analysis (HCA) with molecular descriptors obtained from semiempirical parametric method 3 (PM3) calculations. By applying selected molecular descriptors it was possible to classify active and inactive compounds with accuracy up to 92% and also to suggest the activity of new untested molecules. These descriptors have been only recently discussed in the literature as new possible universal parameters for defining the biological activity of several classes of compounds. (c) 2006 Elsevier Inc. All rights reserved.25691292

A theoretical investigation on the dual-mode photoswitching mechanism of some chiroptical systems

The synthesis of dual-mode optical molecular switching systems has been recently achieved. These systems were based on chiral helical-shaped alkenes in which the chirality can be reversibly modulated by light. In this work we report a theoretical study on the geometric and spectroscopic properties of these structures using the well-known semiempirical methods PM3 (parametric method 3) and ZINDO/S-CI (Zerner's intermediate neglect of differential overlap/spectroscopic-configuration interaction). Our results show that there are two stable conformers very close in energy for each possible molecular helicity presenting a barrier of similar to 40 kcal/mol for bond rotation along the main molecular axis. Under protonation these barriers increase significantly and might explain why the protonation leads to the blocking of the switching process. We propose a scheme for the switching mechanism based on charge transfer and conformational changes during the isomer interconversion.105358334833

Semiempirical study on the electronic structure of antitumor drugs ellipticines, olivacines and isoellipticines

Ellipticine [5,11-dimethyl-6H-pyrido[4,3]carbazole] is a planar organic compound isolated from the plant extract of Ochrosia elliptica, with a high degree of antitumor and cytotoxic activity. Ellipticine and its derivatives have different modes of action, which may include intercalation or covalent binding to DNA and interference with the activity of topoisomerase II. In the present work we studied the electronic, geometrical and spectroscopic properties of 31 ellipticine derivatives and analogue compounds, using the semiempirical methods Parametric Method 3 and Zerner's Intermediate Neglect of Differential Overlap. The Zero Differential Overlap semiempirical Molecular Electrostatic Potential (MEP) was also calculated in order to interpret the electronic structure of the molecules. For the biologically tested ellipticines and olivacines we have observed a rule based on the dipole moment values and a selective distribution of active sites (coming from the MEP calculations) that can be used to identify the active molecules. These results provide a pattern which can be used to select potentially active molecules from the untested group of molecules and to design new ellipticine derivatives with improved antitumor activity. (C) 2004 Elsevier B.V. All rights reserved.71041699515

Electronic indices from semi-empirical calculations to identify carcinogenic activity of polycyclic aromatic hydrocarbons

Recently we have shown that it is possible to group and identify the carcinogenic activity of the polycyclic aromatic hydrocarbons (PAHs) using very simple rules derived from simple Huckel calculations. In this work we have carried out similar calculations using semi-empirical methods in order to investigate whether the derived rules are method dependent. We present PM3 (Parametric Method 3) and ZINDO-CI (Zerner Intermediate Neglect of Differential Overlap-Configuration Interaction) study on the electronic structure of PAHs, Very similar rules, based on the concept of electronic local density of states over specific molecular regions, are derived from PM3 calculations showing that they are essentially method independent. The analysis of the ZINDO-CI results for the intensity of the threshold transitions (first optical transitions) and the composition of the CI contributions also show a differentiated behavior for the strong carcinogenic molecules and the inactive ones. (C) 2000 Elsevier Science B,V. All rights reserved.505556

NUMERICAL STUDY OF TRANSPORT IN A DISSIPATIVE MEDIUM

A numerical study of propagation of a particle through a one-dimensional dissipative medium is presented. The medium is composed of several dissipative sections, which are characterized by their friction coefficients eta. In particular, we have considered two types of friction coefficients distributed orderly or disorderly along the chain. For the same relative proportion of the coefficients, we have found that transport can be enhanced in the disordered distribution in comparison with the ordered one. We also show how this can be considered an approximated way to treat the propagation in a dissipative medium with a position-dependent friction coefficient

Some electronic properties of saturated and unsaturated cubane oligomers using DFT-based calculations

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Cubanes and cubane-based molecular structures attract considerable interest as structural units which represent a new class of materials with remarkable properties. These structures are potentially useful for a variety of industrial applications and, for this reason, deserve detailed study. One of the options is to use cubane-based structures to synthesize a new class of conducting polymers with small energy band gap. In the present work we use the DFT-based methods to perform geometrical optimization and obtain some electronic properties for cubane, cubatriene, saturated and unsaturated oligomers containing different number of cubane and cubatriene building units. Our results indicate that the energy difference between the lowest unoccupied molecular orbital (LUMO) and the highest occupied molecular orbital (HOMO) manifests a small decrease with the growing units number for saturated or unsaturated oligomers. This energy difference is strongly dependent on the presence of hydrogen atoms and is greater for unsaturated structures. (C) 2008 Elsevier B.V. All rights reserved.868416993741Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)FAP-EMIGFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Instituto do Milenio de Nanotecnologia/ MCT (Brazil)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP