Mircea 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).

Comparative QSAR study with electronic and steric parameters for cAMP derivatives with large substituents in positions 2, 6 and 8

Abstract In order to discern structural characteristics for specific activation of four sites, AI and BI on cAK-I and AII and BII on cAK-II, an extended study on a series of cAMP derivatives with large substituents in positions 2, 6 and 8, has been performed. The effect of charged (at pH ≈ 7) substituents upon the corresponding receptor affinities has also been investigated. The MTD method was used together with the estimated hydrophobicities of the base moiety and the charge on the substituent at the 6-(purinic)-position (calculated by the AM1 method) as supplementary structural parameters. For the multiparametric correlations, r values between 0.73 and 0.98 were obtained, while in a cross-validation-like procedure, the r CV 2 values are between 0.36 and 0.64.

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.

Aromatic heterocycles XII. Semiempirical PM3 study of Diels-Alder cycloaddition reaction of substituted phosphabenzenes

We report the results of a semiempirical PM3 study of the 1,4 cycloaddition reaction of substituted λ3-phosphabenzenes with alkynes. The influence of the nature, position and steric hindrance of substituents on the reaction energy is studied. Except for some values, the results are in reasonable agreement with experimental observations and electronic effects of substituents.

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.

XIII. Phosphorus Macrocycles–Theoretical Study

A theoretical study of silacalix[n]phosphinine, n = 3,4 at semiempirical level RHF approximation was performed. Molecular conformation, obtained as local minimum from semiempirical calculation, bond distances and bond angles are in good agreement with X-ray experimental geometry. The values of total energies showed silacalix[4]phosphinine more stable but heats of formation emphasized silacalix[3]phosphinine more stable thermodynamically. Complexation abilities were appreciated by assignment of n andπ∗levels of silacalix[n]phosphinine. Result an improvement ofσ-donating properties and goodπ-acceptor character was kept.

Semi‐Empirical PM3 Study On The Complexation Of α‐Cyclodextrin With 5‐Flucytosine

The paper describes the use of quantum semi‐empirical PM3 calculations to establish the equilibrium geometry of a stable inclusion complex formed of 5‐flucytosine and α‐cyclodextrin. The global minima on the potential energy surface can be obtained in several steps. Some intermolecular parameters (ex.: the distance between the two studied molecules and the orientation of 5‐flucytosine in the α‐cyclodextrin cavity) are artificially modified in each step. A stable inclusion complex was obtained when the 5‐flucytosine is partially included into the α‐cyclodextrin cavity by the primary amino group.

Aromatic λ3 heterocycles XIV. Fosfinine-ether macrocyclesheterocycles XIV. Fosfinine-ether macrocycles

The geometry and electronic structure of several phosphinine-ether macrocycles were investigated at semiempirical level. The calculated geometries are in good agreement with experimental data. Compared to phosphinine, the coordinative abilities of phosphinineether macrocycles based on energy considerations suggest a little lowered π acceptor character, while π donor character is improved. The molecular environment causes a significant mixing of phosphinine and phenyl substituent π levels. The geometry and electronic properties of phosphinine-ether macrocycles can provide significant host coordination properties for guest species.