The molecular orbital INDO method is used for the calculation of long-range NMR proton-proton coupling constants between H1, and protons of the base and between the protons of the furanose ring in purine and pyrimidine nucleosides. The computations show that the couplings between H1, and the protons of the base are negligible in the purine nucleosides and are very sensitive to the torsion angle about the glycosidic bond in pyrimidine nucleosides. For uridine and its derivatives the calculated J 1, 5 are in agreement with experiment for an anti conformation of these compounds. For α- and β-pseudouridines, J1, 6 is important and may be large for anti as well as syn conformations. The long-range couplings between the protons of the furanose ring vary little with the puckering of the sugar.

Measurements of the dipole moments and the electronic spectra of suitably substituted derivatives of xanthine and purine confirm the predictions, obtained by various methods of calculation, that the tautomeric forms of these two bases [N(7)H and N(9)H] have different dipole moments and that the N(7)H forms should be bathochromic as compared with the N(9)H ones.

The overlap multipole expansion procedure is ptilized for the evaluation of the electrostatic molecular potential of poly(dC·dC) and poly(dA·dT). lt is shown that the two sequences of base pairs produce different effects in the significant regions of DNA. In the inner regions of the double helix the potentials are deeper in the major groove than in the minor groove in poly(dG·dC), and the reverse is true in poly(dA·dT). At large distances from the helical axis the regions of the backbone and the minor groove are preferred. The shielding of the phosphate groups by Na+ ions is shown to have an important effect on the discrimination between the two grooves. The region of the minor groove presents always a negative potential for the sequences considered (up to the explored distance of I7 Å from the helical axis), while negative and positive values of the potentials occur, within that distance, in the region of the major groove.

SCF ab-initio molecular orbital calculations on a model of the glyoxylase metabolism of methyl glyoxal to lactic acid are presented. Possible reaction pathways are described and the importance of a magnesium ion and of a basic amino acid residue at the active site of the enzyme glyoxylase I, suggested by experimental studies, is investigated.

SO ab initio computations in the supermolecule approach have been carried out on the interaction of the PO4H2− anion with the hexahydrate, pentahydrate, and tetrahydrate of Na+ and Mg2+. The interaction with the hexahydrates corresponds to a “through-water” association; the interactions with the lesser hydrates represent “direct” binding of the partially dehydrated cation with the anion. At these levels of hydration, the two types of interaction appear competitive with some advantage for the through-water binding. Examples from x-ray crystallographic studies of biological ligands substantiate the possible multiplicity of the binding processes. A small charge transfer for Na+ and a much larger one for Mg2+ exists in the hydrates, from the water molecules toward the cations. The net excess of charge on the cations is only slightly perturbed in the adducts with PO4H2−.

The magnetic shielding constants of. carbon 13 and hydrogen nuclei of the dimethylphosphate anion are calculated for the gauche-gauche and gauche-trans conformations of the molecule as a function of the rotational angles about the PO and CO bonds. The results obtained show that for the protons the value of the rotational angle about the CO bond is more important than that about the PO bond. For carbon 13 of the two methyl groups of the molecule the gt conformation corresponds to magnetic shielding constants which are shifted downfield with respect to their values for the gg conformation. These results are discussed in relation to the role of the variations of some of the conformational parameters of the ribose phosphate backbone of polynucleotides in the nuclear magnetic resonance spectra of this type of molecule.

Quantum-mechanical studies, using the PCILO method, have been carried out on the conformational properties of formycin (both neutral and protonated), formycin B, oxoformycin B, and showdomycin with respect to XCN (whether anti or syn) and ΦC4′-C5′ (whether gg, gt, or tg). The results indicate that for neutral formycin, FMB, and oxoformycin B, the intrinsically preferred conformation is syn for XCN associated with gg for ΦC4′-C5′, while for protonated formycin and showdomycin, an anti conformation for XCN associated with the gg conformation for ΦC4′-C5′ is favored. The results also indicate the high probability for neutral formycin to adopt an anti conformation and support the dual behavior of neutral formycin as proposed by Ward and coworkers in order to explain the anomalous properties of formycin nucleotides and polynucleotides. The PCILO predictions for OXOFMB agree well with the observed crystallographic conformation. For the other compounds, the crystallographic conformation is attributed to inter- and intramolecular hydrogen bonding and packing forces in the crystal. Recent nuclear magnetic resonance results on neutral formycin and FMB show that the intrinsically preferred conformation (syn, gg) is observed for these molecules in solution.

On the basis of several parameters calculated quantum chemically an explanation is proposed for the relative reactivity of a range of aldehydes toward acid catalyzed hydration. In particular the biochemically interesting species of glyoxal and methylglyoxal are studied and compared to other aldehydes.

International Journal of Quantum ChemistryVolume 3, Issue S3A p. 83-102 Article Conjugated systems in biology Bernard Pullman, Bernard Pullman Institut de Biologie Physico-chimique, (Fondation Edmond de Rothschild), 13, rue P. et M. Curie, Paris 5eSearch for more papers by this author Bernard Pullman, Bernard Pullman Institut de Biologie Physico-chimique, (Fondation Edmond de Rothschild), 13, rue P. et M. Curie, Paris 5eSearch for more papers by this author First published: 13/18 January 1969 https://doi.org/10.1002/qua.560030714Citations: 1AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume3, IssueS3ASupplement: Proceedings of the International Symposium on Atomic, Molecular, and Solid-state Theory and Quantum Biology13/18 January 1969Pages 83-102 RelatedInformation

Anthraquinone intercalators possessing two side chains offer potentially the three possibilities of having these chains located (1) both in the major groove, (2) both in the minor groove, and (3) one in the major and the other in the minor groove ("threading" mode of intercalation). Computations carried out on two related doubly substituted anthraquinones, mitoxantrone (I) and bis-glycylglycylanthraquinone (II), indicate that while I should intercalate with its two side chains located both in the major groove, II should adopt the threading arrangement. This result is interpreted in terms of the importance of ligand-DNA mutual adaptation. The results of the computations are in agreement with very recent experimental findings of Palumbo and Gatto at the University of Padova in Italy.

To summarize the significance of the Sanibel Symposia in the field of "Structure and Activity of Biomolecules" is a Herculean task, meaning summarizing 30 years of the development of Quantum Biology in 30 minutes, which gives 1 minute per year. How does one do it? There are obviously many ways in which this cannot be done. One a priori conceivable way was to determine the most important (in the lecturer's eyes) contribution, discovery or paper for each of these consecutive 30 years and to present a list of potential laureates of what we could consider as an imaginary yearly Lowdin Prize. The author has tried the game but found it impracticable. A more reasonable solution seemed to be to trace the history of the main intellectual lines in the methods and themes which prevailed in the development of our knowledge on the Structural and Activity of Biomolecules during the period involved. It quickly turned out, however, that the scope was again so wide and its snapshot representation, the only feasible one, so dense and compact that it would have been reduced to the mere enumeration of the dozens of important, fundamental techniques and problems which have been dealt with during that time. So the author gave up this project too. Finally, after much hesitation, his choice went to a third procedure: the selection of the most important intellectual concept which had the most important impact on the development of the quantum-mechanical contribution to our understanding of structure-activity relationship in biomolecules. I believe this concept to be that of the electrostatic molecular potential, the introduction of which enabled the decisive step of moving over from the study of the structure and activity of small biomolecules or small constituents of the fundamental biomacromolecules to the study of these properties in the biomacromolecules themselves. Examples will be given which illustrate this opinion.

The author presents results of recent computations on the DNA sequence specificity of four types of antitumor drugs which have been relatively little explored theoretically till now. 1) analogues of the classical groove binding ligand distamycin A in which the heteroaromatic rings are replaced by hydrocarbon units (benzene rings or saturated β-alanine moieties), 2) tetracationic porphyrins, 3) dicationic steroid diamines and 4) aurelic acid derived antibiotics. Some of these groups have been actively investigated experimentally by authors present at this meeting.