Maria Mracec

QSAR study with steric (MTD), electronic and hydrophobicity parameters on psychotomimetic phenylalkylamines

Abstract Multiple linear regression analysis has been used to identify the most important properties relevant to psychotomimetic activity displayed by 37 phenylalkylamines. Using the minimal topologic differences (MTD) parameter, lipophilicity (log P, calculated by using π Hansch substituent terms), average electrostatic field (AEF) and electronic descriptors, lowest unoccupied molecular orbital energies (ELUMO) and net atomic charges (obtained from AM1 calculations), good correlations with biological activity were obtained (R2 = 0.79 − 0.92). Cross-validation procedure was applied indicating a good predictability of the proposed models (R2cv = 0.67 − 0.81).

Structural determinants of the alpha2 adrenoceptor subtype selectivity.

Alpha2-adrenergic receptor (α2-AR) subtypes, acting mainly on the central nervous and cardiovascular systems, represent important targets for drug design, confirmed by the high number of studies published so far. Presently, only a few α2-AR subtype selective compounds are known. Using homology modeling and ligand docking, the present study analyzes the similarities and differences between binding sites, and between extracellular loops of the three subtypes of α2-ARs. Several α2-AR subtype selective ligands were docked into the active sites of the three α2-AR subtypes, key interactions between ligands and receptors were mapped, and the predicted results were compared with the available experimental data. Binding site analysis reveals a strong identity between important amino acid residues in each receptor, the very few differences being the key toward modulating selectivity of α2-AR ligands. The observed differences between binding site residues provide an excellent starting point for virtual screening of chemical databases, in order to identify potentially selective ligands for α2-ARs.

Structure simulation into a lamellar supramolecular network and calculation of the metal ions/ligands ratio

BackgroundResearch interest in phosphonates metal organic frameworks (MOF) has increased extremely in the last two decades, because of theirs fascinating and complex topology and structural flexibility. In this paper we present a mathematical model for ligand/metal ion ratio of an octahedral (Oh) network of cobalt vinylphosphonate (Co(vP)·H2O).ResultsA recurrent relationship of the ratio between the number of ligands and the number of metal ions in a lamellar octahedral (Oh) network Co(vP)·H2O, has been deducted by building the 3D network step by step using HyperChem 7.52 package. The mathematical relationship has been validated using X ray analysis, experimental thermogravimetric and elemental analysis data.ConclusionsBased on deducted recurrence relationship, we can conclude prior to perform X ray analysis, that in the case of a thermogravimetric analysis pointing a ratio between the number of metal ions and ligands number around 1, the 3D network will have a central metal ion that corresponds to a single ligand. This relation is valid for every type of supramolecular network with divalent metal central ion Oh coordinated and bring valuable information with low effort and cost.

Mixed-Ligand Complexes of Co(II) and Cu(II) with Pyrazoeon1C Mannich Bases and 2-aminobenzothiazole

Abstract Mixed-ligand complexes of the type M2L(TAB)nX4 [L = N,N′-bis(4-antipyryl-methyl)piperazine (BAMP), or N,N′-tetra(4-antipyrylmethyl)-l,2-diaminoethane (TAMEN) and 2-aminobenzothiazole (TAB), X - NCS or CIO4, M - Co, n - 2, or M - Cu, n = 4] were synthesized and investigated. The IR and Raman spectra revealed that the ligands L are coordinated through the carbonyl oxygen atom of the antipyrine and the nitrogen atom of the piperazine or 1,2-ethanediaminc bridge, except in Cu2(TAMEN)(TAB)4(ClO4)4, in which case TAMKN is coordinated to the metal only through the carbonyl oxygen. Steric considerations explain the bonding of TAB through the exocyclic or endocyclic nitrogen.

Modeling of dexmedetomidine conformers and their interactions with alpha2 adrenergic receptor subtypes

Dexmedetomidine (4-[(S)-1-(2,3-dimethyl-phenyl)-ethyl]-1H-imidazole), Dex, is potent agonist acting on α2-adrenergic receptors (α2-ARs). It can exist at the physiological pH in both forms: neutral and protonated. The results of receptor-independent and receptor-dependent studies applied to both forms of Dex are reported. A conformational analysis with PM3 semiempirical MO and ab initio HF/6-31G* methods was carried out for both forms of Dex. The calculated geometries of low-energy conformers of Dex were compared with X-ray geometry and those of conformers resulted from molecular docking of Dex in the binding pockets of 3D homology models of the α2A-, α2B-, and α2C-adrenoceptor subtypes. A MM/QM (molecular mechanics/quantum mechanics) docking study was performed to refine and optimize receptor–ligand complex and close contacts between the ligand and amino acids lining the binding cavity. Two-dimensional potential energy surface and docking results suggest that the imidazole ring can easily adopt the best orientation for an efficient interaction with the carboxylate group of Asp3.32 from the binding cavity of alpha2 adrenergic receptor subtypes.

A QSAR study using MTD method and Dragon descriptors for a series of selective ligands of α2C adrenoceptor.

A QSAR (quantitative structure-activity relationship) analysis of the binding affinities for a series of 43 quinoline derivatives active against the alpha2C adrenergic receptor was performed. Multiple linear regressions (MLR) were obtained using the minimum topological difference (MTD) descriptor and various descriptors which were calculated with Dragon3.0. The variable selection was performed either through the forward stepwise method or backward stepwise combined with forward stepwise methods, providing two satisfactory models. The first one, obtained as a result of the forward stepwise method, contains MTD, Mor24v, MATS5m, MATS7m, G3m, L1s, G_N_N descriptors, while the other one obtained through the combination of backward and forward stepwise methods contains the following descriptors: MTD, ZM2V, X5V, IC5, MATS4v, and E2u. Both models highlight the importance of steric interactions and can be used as tools for predicting the binding affinity of related compounds.

Significance of MTD and other descriptors in lipophilicity models for chlorinated aromatic compounds.

Abstract The lipophilicity of chlorinated benzenes and 20 biphenyls has been modeled using the minimum topological difference method and MTD indices. The MTD descriptor has been optimized on its own or together with nCl (number of chlorine atoms per molecule). 2D and 3D-descriptors such as van der Waals surface area and volume, solvent accessible surface area and solvent-accessible surface-bounded molecular volume, and the inter-planar angle of the substituted biphenyls. In lipophilicity models of chlorinated aromatic compounds the majority of descriptors, including MTD, contain essentially the information of nCl. MTD is a good lipophilicity descriptor of chlorinated aromatic compounds either alone or in association with other descriptors. For chlorobenzenes it gives r = 0.998, s =0.069, F = 2281, and for the set of chlorinated biphenyls r = 0.974, s = 0.255, F = 338, a better result than gives the nCl descriptor (r = 0.967). The significance of MTD descriptor in different models is discussed. Beside nCl, the MTD index encodes ortho and para effects.