Graciela N. Zamarbide

QSAR Study and Molecular Design of Open-Chain Enaminones as Anticonvulsant Agents

Present work employs the QSAR formalism to predict the ED50 anticonvulsant activity of ringed-enaminones, in order to apply these relationships for the prediction of unknown open-chain compounds containing the same types of functional groups in their molecular structure. Two different modeling approaches are applied with the purpose of comparing the consistency of our results: (a) the search of molecular descriptors via multivariable linear regressions; and (b) the calculation of flexible descriptors with the CORAL (CORrelation And Logic) program. Among the results found, we propose some potent candidate open-chain enaminones having ED50 values lower than 10 mg·kg−1 for corresponding pharmacological studies. These compounds are classified as Class 1 and Class 2 according to the Anticonvulsant Selection Project.

Peptide models XXIV: An ab initio study on N-formyl-L-prolinamide with trans peptide bond. The existence or non-existence of αL and ϵL conformations

Abstract N-formyl-L-prolinamide was subjected to geometry optimization at three levels of theory: HF/3-21G, HF/6-31G (d) and B3LYP/6-31G (d). At all three levels of computation the global minimum was γ L (inverse γ -Turn) backbone conformation with two ring-puckered forms “UP” and “DOWN”. At HF/3-21G level of theory three backbone conformations were found γ L , ϵ L , and α L . At higher levels of theory the ϵ L , and α L conformations disappeared. The “UP” and “DOWN” ring-puckered forms, in the γ L backbone conformation, led to practically identical vibrational spectra at the B3LYP/6-31G (d) level of theory.

Peptide models XXIX. cis-trans Isomerism of peptide bonds: ab initio study on small peptide model compound; the 3D-Ramachandran map of formylglycinamide

Thermodynamic separations for cis and trans-amides and formylglycinamide range from 0.00 to 4.77 kcal/mol as computed at various levels of theory. The barriers for trans! cis-isomerization, for the same set of compounds, computed at various levels of theory, were found between 15.69 and 22.67 kcal/mol. The cis- and trans-Ramachandran maps of formylglycinamide are compared and the topology of the ab initio 3D-Ramachandran map is presented for the first time.q 2000 Elsevier Science B.V. All rights reserved.

Characteristics of Ramachandran maps of L-alanine diamides as computed by various molecular mechanics, semiempirical and ab initio MO methods. A search for primary standard of peptide conformational stability

Abstract The optimized geometries and relative energies obtained by four force field and two semi-empirical methods were compared with ab initio results computed for formyl- L -alaninamide. Not all methods yielded the same number of minimum energy conformers. Furthermore, while the optimized geometries of the conformers found were comparable, the computed relative energies varied substantially. Also, the force field calculations produced Ramachandran maps that did not even have the appearance of the ab initio Ramachandran map. Correlating the ab initio relative energies (Δ E ) or free energy (Δ G ) with the log of relative populations, ln( p x / p γ L ), led to linear relationships from which four conformers deviated; two of them (α L and e L ) were overly destabilized and two of them (γ L and γ D ) were over-stabilized. It is suggested that, after such deviations are corrected, a primary standard may be obtained that might be useful in further investigations related to force-field parametrization as well as protein folding.

Geometrical isomerism, tautomerism and conformational charges of 2-propenal-3-amine in its neutral and protonated forms

Abstract Enaminones may be pro-drugs releasing via proton catalyzed hydrolysis a primary amine, which may be an actual drug. The prototype enaminone: 2-propenal-3-amine has been subjected to quantum chemical studies. Its various tautomers and their conformers were investigated in a search for the most likely reactive form. Protonation study revealed the following order of basicity: O>C>N for favorable sites of protonation.

Theoretical studies on sulfanilamide and derivatives with antibacterial activity: conformational and electronic analysis

AbstractQuantum chemical methods have been used to study the conformational and electronic properties of sulfanilamide and derivatives with antibacterial activity. Calculations at B3LYP/6-311++G(3df,2p) level of theory predict the existence of four conformers for sulfanilamide depending on the orientation of p-amino and amide groups. Focusing on the sulfonamide moiety, amide NH2 and SO2 groups could exist either in an eclipsed or staggered arrangement. Gas-phase results predict the eclipsed conformer to be most stable but opposite to what has been rationalized previously, no stabilizing hydrogen bonds between those groups has been found through NBO analysis. When solvent effect is taken into account through the IEF-PCM method, staggered conformer is preferred; in fact, eclipsed conformation changed when explicit solvent molecules were included. Conformational analysis of all derivatives has shown two global minima which are specular images. Five out of the seven derivatives studied adopted a particular minimum energy conformation with very similar geometries. FigureAntibacterial sulfonamides show a large conformational similarity degree.

An exploratory conformational analysis of 3-mercapto-propanamide and 2-methyl-3-mercapto-propanamide as well as their S-deprotonated conjugate basis: an ab initio study

Abstract Ab initio conformational analysis has been carried out on 3-mercapto-propanamide, ( R )- and ( S )-2-methyl-3-mercapto-propanamide as well as their S -deprotonated conjugate basis. They were carried out at the HF/3-21G level of theory. The topology of the conformational potential energy surfaces and hypersurfaces have been analysed.

Stereoelectronic effects and dynamic chirality in ethyl nitrite (Et-ONO) computed at the HF and DFT levels of theory

Abstract The annihilation of the most extended conformer on the comformational potential energy surface of ethyl nitrite is studied and analyzed in terms of the principles of stereoelectronic effects. The dynamic chirality of the prochiral CH 2 moiety in Me–CH 2 –ONO is investigated.