Molecular orbital studies on nucleoside antibiotics X. Conformation of nebularine and isoguanosine

Summary Conformational properties of two nucleoside analogs, namely nebularine and isoguanosine have been investigated by using PCILO (Perturbative Configuration Interaction using Localized Orbitals) method. Nebularine (9--ribofurnosyl purine) is a naturally occurring purine nucleoside which is structurally similar to adenosine and it inhibits the growth of tumor cells and influenza B virus. Isoguanosine is one of the two naturally occurring analogs of guanosine. Both C2-endo and C3-endo sugar puckerings have been considered for both the molecules with preselected values of torsion angles around C2–O2 and C5–O5 bonds. The results indicate that nebularine has conformational preferences very similar to those of its parent nucleoside, adenosine; whereas the conformational properties of isoguanosine are very different from those of guanosine as well as adenosine. The important implications of these results have been discussed in terms of the biological activity of these molecules.     

Molecular orbital studies on nucleoside antibiotics. IV. conformation of 3'-deoxyadenosine (cordycepin) and 3'-amino-3'-deoxyadenosine

PCILO computations have been carried out on the conformation of 3'-deoxyadenosine (cordycepin) and 3'-amino-3'-deoxyadenosine. These nucleoside antibiotics results as a consequence of modification in the sugar part of adenosine. Both C(2')-endo and C(3')-endo sugar puckerings have been considered in the computations and the results obtained indicate that these nucleoside antibiotics have very similar conformational preferences as compared to those of the parent nucleoside adenosine. This similarity which is quite marked in aqueous solution has important biological significance.     

Molecular orbital calculations on the preferred conformation of nucleosides

The extended Hückel theory has been applied to the study of the conformation of the nucleosides of the purine and pyrimidine bases of the nucleic acids. Although the evaluation of the total energy as a function of the rotation angle presents in all cases two minima, the calculations predict a preferred anti conformation for uridine, cytidine and adenosine and a preferred syn conformation for guanosine. These predictions appear to be in agreement with the available experimental data.

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Zusammenfassung Mit der erweiterten Hückel-Theorie wurde die Konformation der Purin- und Pyrimidin-Nucleoside untersucht. Die Gesamtenergie in Abhängigkeit vom Verdrehungswinkel zeigt zwei schwache Minima; für Uridin, Cytidin und Adenosin ist die anti-Konformation bevorzugt, für Guanosin die syn-Konformation. Die Berechnungen sind in Übereinstimmung mit den verfügbaren experimentellen Daten.

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Résumé La méthode de Hückel étendue a été appliquée à l'étude de la conformation des nucléosides des bases puriques et pyrimidiques des acides nucléiques. Bien que l'énergie moléculaire totale présente dans tous les cas deux minima en fonction de l'angle de rotation, la théorie prévoit une conformation préférentielle anti pour l'uridine, la cytidine et l'adénosine et une conformation préférentielle syn pour la guanosine. Ces prédictions paraissent en accord avec les données expérimentales disponibles.

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This work was supported by grant no, 67-00-532 of the Délégation Générale à la Recherche Scientifique et Technique (Comité de Biologie Moléculaire).

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NATO Postdoctoral Fellow in Science 1967–1968.     

Mass spectrometry of nucleoside derivatives. Seleno analogs of purine and pyrimidine bases and nucleosides

Mass spectra of certain selenobases and selenonucleosides, and some of their trimethylsilyl and O,N-permethyl derivatives have been studied from the standpoint of structural characterization, and in order to ascertain the influence of selenium on normal fragmentation patterns. Molecular ion abundances of the selenouracils are intermediate between those of the corresponding oxygen and sulfur analogs. Fragmentation processes are similar to those of the corresponding normal bases and nucleosides but with additional ions resulting from expulsion of Se or SeH in most cases. Trimethylsilylation occurs at approximately the same rate as for normal bases and nucleosides but the products show decreasing stability with prolonged heating. A least squares procedure is demonstrated which generates monoisotopic mass patterns and assists in interpretation of the mass spectra.     

Molecular orbital studies of the thienopyrazines

The calculated reactivity indicies and bond lengths for thieno[2,3-b]- and thieno[3,4-b]-pyrazine are reported.     

Molecular orbital studies on ice-like structures

Molecular orbital (MO) calculations were carried out on a series of ice-I _h and ice-I _c type lattices. These lattices were assigned dimensions which approximate conditions in liquid water (O-O = 2.86 Å) and, in addition, the dimensions of the ice-I _h lattices were changed to ascertain the influence of lattice expansion and contraction. Component parts of several lattices were investigated as were lattices lacking one or two individual monomeric units. Results are in accord with current experimental approximations. As the ice-I _h lattice is expanded, the stabilization energy diminishes. In the liquid model, ice-I _h structures are generally more stable than those of ice-I _c ; component rings of the lattice models of ice-I _c determine the stabilities of these models, and a stable ring system can stabilize an unstable system. An ice-I _h lattice model lacking a single monomer is stable. The trend of charges at the oxygen centres closely correlates with the charges on the central oxygen atom of the appropriate trimer.     

Molecular orbital studies of conformation

The application of single-configuration molecular orbital theory to the conformations of small organic molecules is reviewed. Emphasis is laid on systematic ab initio studies using simple gaussion-type basis sets for expansion of the molecular orbitals. Topics dealt with include the prediction of bond angles, single-rotor potential functions, effects of single and double (1,2) substitutions on such rotors and double-rotor potentials involving two internal rotation coordinates.     

Molecular structure of carbene analogs

The geometrical parameters of all carbene analogs, halocarbenes, and the corresponding tetrahalides obtained from experimental data and high-level quantum-chemical calculations were collected. Trends in their variations are interpreted using the VSEPR model and by consideration of the HOMOs and LUMOs.     

Molecular orbital studies of hydrogen bonds

The ground state, the lowest singlet and triplet n-* states, and the lowest triplet -* state of the formic acid monomer and dimer are studied with the ab initio molecular orbital theory. The two-configuration electron-hole potential method is used for calculations of excited states of dimers. The potential energy curves for the symmetrical simultaneous movement of two bridging protons are studied for all of the states. The barrier of the proton transfer in the ground state is found to be the smallest of the states studied. The association energy is analyzed in terms of various components.A preliminary account has been presented at the First International Congress of Quantum Chemistry, Menton, France, 1973, and has appeared in Ref. [3].     

Molecular orbital studies of polyethylene deformation

Young's modulus E for polyethylene in the chain direction is calculated with molecular orbital theory applied to n-alkanes C₃H₈ through n-C₁₃H₂₈ and analyzed with the cluster-difference method. Semiempirical CNDO, MNDO, and AM1 models and ab initio HF/STO-3G, HF/6-31G, HF/6-31G*, and MP2/6-31G* models are used. Cluster-difference results, when extrapolated to infinite chain length, give E in good agreement with moduli evaluated with molecular cluster or crystal orbital methods, provided minimal basis sets are employed. E decreases from 495 GPa (CNDO) to 336 GPa (MP2/6-31G*) as the level of theory is improved, consistent with established behaviors of the various models. Our calculations do not reproduce earlier molecular cluster or crystal orbital results, which gave E < 330 GPa. The most rigorous MP2/6-31G* model is known to overestimate force constants by ∼ 11%; the scaled modulus E = 299 GPa is in good accord with E = 306 GPa from recent calculations based on experimental vibration frequencies. © 1996 John Wiley & Sons, Inc.