Theoretical studies on penicillins, penicillin sulphones and their 1-oxa-1-dethia and 1-carba-1-dethia analogues: binding specificities of transeptidases and penicillinases

Empirical potential energy calculations have been carried out to determine the preferred conformations of penicillins and penicillin sulphones and their 1-oxa-1-dethia and 1-carba-1-dethia analogues. With the exception of 1-oxa-1-dethia penicillins, all the other compounds favour C2 and the C3 puckered conformations of their five-membered rings. Replacement of C2 methyl groups by hydrogen atoms as in bisnorpenicillin V or oxidation of sulphur in position 1 as in sulphones, makes the C3 puckered form much less favourable. Addition of an amino-acyl group at the C6 atom, however, makes the C3 puckered form more favoured in penicillin G or V and in 1-carba-1-dethia penicillins. Through the replacement of the sulphur atom at position 1 by an oxygen atom or by a -CH2 group increases the non-planarity of the lactam peptide bond, it significantly affects the relative disposition of the C3 carboxyl group with respect to the β-lactam ring. These conformational differences have been correlated with the biological activities of these compounds. The present study suggests that the conformation of the bicyclic ring system may be more important for initial binding with the crosslinking enzyme(s) involved in the biosynthesis of bacterial cell-wall peptidoglycan and that the mode of binding is influenced by the nature of the side-group at the C6 atom. These studies predict, in agreement with experimental results, that the 1-oxa-1-dethia penicillin nulceus is an inhibitor of penicillianses. The study also suggests that the stereospecificities of the crosslinking enzyme(s) and penicillinases are very similar with regard to the nature of the side-group at the 6 atom and the confirmation of the bicyclic ring system. However, the confirmational requirement for the bicyclic ring system appears to be more specific in the former enzyme than in the latter.

Crystal Physics, Diffraction, Theoretical and General Crystallography

A formula has been derived for the mean-square error in the phases of crystal reflections determined through the multiwavelength anomalous scattering method. The error is written in terms of a simple function of the positions in the complex plane of the 'centres' corresponding to the different wavelengths. For the case of three centres, the mean-square error is inversely proportional to the area of the triangle formed by them. The theoretical values are in good agreement with those obtained by earlier workers from computer simulations. The present method makes it easier to optimize the number and the actual wavelengths to be employed in the multiwavelength method. The maximum benefits of this method are expected in experiments employing synchrotron radiation or neutrons.

X-Pro peptides. A theoretical study of the hydrogen bonded conformations of (a-aminoisobutyryl-L -prolyl)n sequences

Intramolecularly hydrogen bonded conformations of (Aib-Pro)n sequences have been analysed theoretically. Both 4�1 (C10 and 3�1 (C7 hydrogen bonded regular structures are shown to be stereochemically feasible. Conformational energies for the helical structures have been estimated using classical potential energy methods. Both C10 and C7 conformations have very similar energies. Pyrrolidine ring puckering has a pronounced effect on the energies, and only Cγ-endo puckered Pro residues can be accommodated. The theoretical calculations using spectroscopic data suggest that the recently proposed novel 310 helical conformation for benzyloxycarbonyl(Aib-Pro)4-methyl ester is in solution, is indeed energetically and stereochemically favourable.

Theoretical studies on the conformations of aldopentopyranose tetraacetates

Abstract is not available.

Theoretical gain optimization studies in 10.6 µm CO2-N2 gasdynamic lasers. IV. Further results of parametric study

Based on a method proposed by Reddy and Shanmugasundaram, similar solutions have been obtained for the steady inviscid quasi-one-dimensional nonreacting flow in the supersonic nozzle of CO2-N2-H2O and CO2-N2-He gasdynamic laser systems. Instead of using the correlations of a nonsimilar function NS for pure N2 gas, as is done in previous publications, the NS correlations are computed here for the actual gas mixtures used in the gasdynamic lasers. Optimum small-signal optical gain and the corresponding optimum values of the operating parameters like reservoir pressure and temperature and nozzle area ratio are computed using these correlations. The present results are compared with the previous results and the main differences are discussed. Journal of Applied Physics is copyrighted by The American Institute of Physics.

Conformational Choices for the Stereochemically Constrained gamma-Amino Acid Residue Gabapentin: Theoretical Studies and Correlation With Experimental Results

Gabapentin (1-aminomethylcyclohexaneacetic acid, Gpn) is an achiral, conformationally constrained gamma amino acid residue. A survey of available crystal structures of Gpn peptides reveals that the torsion angles about the C-gamma-C-beta (theta(1)) and C-beta-C-alpha(theta(2)) bonds are overwhelmingly limited to gauche, gauche (g(+)g(+)/g(-)g(-)) conformations. The Gpn residue forms C-7 and C-9 hydrogen bonds in which the donor and acceptor atoms come from the flanking peptide units. In combination with alpha amino acid residues alpha gamma and gamma alpha segments can adopt C-12 hydrogen bonded structures. The conformational choices available to the Gpn residue have been probed using energy calculations, adopting a grid search strategy. Ramachandran phi-psi maps have been constructed for fixed values of theta(1) and theta(2), corresponding to the gauche and trans conformations. The sterically allowed and energetically favorable regions of conformational space have been defined and experimental observations compared. C-7 and C-9 hydrogen bonded conformational families have been identified using a grid search approach in which theta(1) and theta(2) values are varied over a range of +/- 10 degrees about ideal values at 1 degrees intervals. The theoretical analysis together with experimental observations for 59 Gpn residues from 35 crystal structures permits definition of the limited range of conformational possibilities at this gamma amino acid residue. .

Theoretical gain optimization in CO2-N2-H2 gasdynamic lasers with two-dimensional wedge nozzles

Attention is given to the results of optimization studies with a 16-micron CO2-N2-H2 GDL employing two-dimensional wedge nozzles. The optimum value of the achievable gain reaches 12.7 percent/cm on the P(15) line for a 30:50:20 percent respective apportionment of the aforementioned gases. The corresponding optimum values for reservoir pressure and area ratio are computed as functions of reservoir temperature, and presented graphically.

Theoretical calculations of base-base interactions in nucleic acids: II Stacking interactions in polynucleotides

Base-base interactions were computed for single- and double- stranded polynucleotides, for all possible base sequences. In each case, both right and left stacking arrangements are energetically possible. The preference of one over the other depends upon the base-sequence and the orientation of the bases with respect to helix-axis. Inverted stacking arrangement is also energetically possible for both single- and double-stranded polynucleotides. Finally, interaction energies of a regular duplex and the alternative structures3 were compared. It was found that the type II model3 is energetically more favourable than the rest.

Theoretical calculations of base-base interactions in nucleic acids: I Stacking interactions in free bases

Stacking interactions in free bases were computed on the basis of molecular association. The results of the calculations were compared with the stacking patterns observed in a few single crystals of nucleic acid components as examples. The following are the conclusions: (i) there can be two types of stacking pattern classified as normal and inverted types for any two interacting bases and both can be energetically favourable (ii) in both the types the stacking interaction is a combined effect of the overlap of the interacting bases and relative positions and orientations of the atomic centres of the two bases (iii) crystal symmetry and H-bonding interaction may influence stacking patterns.

Which One Is Preferred: Myers-Saito Cyclization of Ene-Yne-Allene or Garratt-Braverman Cyclization of Conjugated Bisallenic Sulfone? A Theoretical and Experimental Study

A competitive scenario between Myers-Saito (MS) and Garraff-Braverman (GB) cyclization has been created in a molecule. High-level computations indicate a preference for GB over MS cyclization. The activation energies for the rate-determining steps of the GB and MS cyclizations were found to be the same (24.4 kcal/mol) at the B3LYP/6-31G* level of theory; thus, from the kinetic point of view, both reactions are feasible. However, the main biradical intermediate GB2 of the GB reaction is 6.2 kcal/mol lower in energy than the biradical MS2, which is the main intermediate of MS reaction, so GB cyclization is thermodynamically favored over MS cyclization. To verify the prediction by computational techniques, bisenediynyl sulfones 1-4 and bisenediynyl sulfoxide 17 were synthesized. Under basic conditions, these molecules isomerized to a system possessing both the ene-yne-allene and the bisallenic sulfone. The isolation of only one product, identified as the corresponding naphthalene- or benzene-fused sulfone 8-11, indicated the occurrence of GB cyclization as the sole reaction pathway. No product corresponding to the MS cyclization pathway could be isolated. Though the theoretical prediction showed a preference for the GB pathway over the MS pathway, the exclusive preference for GB over MS cyclization is very striking. Further analysis showed that the intramolecular self-quenching nature of the GB pathway may play an important role in the complete preference for this reaction. Apart from the mechanistic studies, these sulfones showed DNA cleavage activity that had an inverse relation with the reactivity order. Our findings are important for the design of artificial DNA-cleaving agents.

Simple theoretical analysis of the Einstein's photoemission from quantum confined superlattices

In this paper, we study the Einstein's photoemission from III-V, II-VI, IV-VI and HgTe/CdTe quantum well superlattices (QWSLs) with graded interfaces and quantum well effective mass superlattices in the presence of a quantizing magnetic field on the basis of newly formulated dispersion relations in the respective cases. Besides, the same has been studied from the afore-mentioned quantum dot superlattices and it appears that the photoemission oscillates with increasing carrier degeneracy and quantizing magnetic field in different manners. In addition, the photoemission oscillates with film thickness and increasing photon energy in quantum steps together with the fact that the solution of the Boltzmann transport equation will introduce new physical ideas and new experimental findings under different external conditions. The influence of band structure is apparent from all the figures and we have suggested three applications of the analyses of this paper in the fields of superlattices and microstructures.

Theoretical Investigation on the Effect of Different Nitrogen Donors on Intramolecular Se center dot center dot center dot N Interactions

The effect of different donor nitrogen atoms on the strength and nature of intramolecular Se center dot center dot center dot N interactions is evaluated for organoselenium compounds having N,N-dimethylaminomethyl (dime), oxazoline (oxa) and pyridyl (py) substituents. Quantum chemical calculations on three series of compounds [2-(dime)C6H4SeX (1a-g), 2-(oxa)C6H4SeX (2a-g), 2- (py)C6H4SeX (3-ag); X=Cl, Br, OH, CN, SPh, SePh, CH3] at the B3LYP/6-31G(d) level show that the stability of different conformers depends on the strength of intramolecular nonbonded Se center dot center dot center dot N interactions. Natural bond orbital (NBO), NBO deletion and atoms in molecules (AIM) analyses suggest that the nature of the Se center dot center dot center dot N interaction is predominantly covalent and involves nN ->sigma*(Se-X) orbital interaction. In the three series of compounds, the strength of the Se center dot center dot center dot N interaction decreases in the order 3>2>1 for a particular X, and it decreases in the order Cl > Br > OH>SPh approximate to CN approximate to SePh>CH3 for all the three series 1-3. However, further analyses suggest that the differences in strength of Se center dot center dot center dot N interaction in 1-3 is predominantly determined by the distance between the Se and N atoms, which in turn is an outcome of specific structures of 1, 2 and 3, and the nature of the donor nitrogen atoms involved has very little effect on the strength of Se center dot center dot center dot N interaction. It is also observed that Se center dot center dot center dot N interaction becomes stronger in polar solvents such as CHCl3, as indicated by the shorter r(Se center dot center dot center dot N) and higher E-Se center dot center dot center dot N values in CHCl3 compared to those observed in the gas phase.