Physics & Astronomy ETDs

Publication Date

3-29-1977

Abstract

Extended Hueckel theory (EHT) was used to study analogs of sugar rings in nucleic acid monomers. The energy gradient in a variable metric algorithm was used to find the potential energy along the pseudorotation path. Use of the energy gradient made it possible to permit 34 degrees of freedom in a molecule. Seven molecules and their isomers were studied. These were: 3-hydroxy2-methyl tetrahydrofuran, 2-ami no-4-hydroxytetrahydrofiJran, 5-ami no3-hydroxy-2-methyltetrahydrofuran (deoxyribonucleic acid analog), 3,4-dihydroxy-2-methyltetrahydrofuran, 2-amino-3,4-dihydroxytetrahydrofuran, 2-amino-5-methyltetrahydrofuran, and 2-amino-3,4-dihydroxy-5-methyltetrahydrofuran (ribonucleic acid analog).

It was shown that the difference in sum of total overlap populations (TOP) for all pairs of atoms between two related conformations of a molecule correlates well with the difference in total energy for the same two conformations. The TOP's were used as a means of studying interaction between different molecule segments.

The experimental conformations of nucleic acid-monomers obtained from X-ray crystallography were studied. Special attention was paid to the sugar conformations. The interrelationships of sugar conformation, backbone and side conformations, sugar type, base type, and substituents were discussed. Patterns were pointed out.

Bond length representation of EHT is known to be poor. Therefore,in all EHT computations on molecules carried out in this dissertation bond lengths were kept fixed. In most calculations, due to deficiency of EHT, the C-0-C ring angle was also kept fixed.

For the B conformation of the deoxyribonucleic acid sugar analog one global minimum was found. This seemed to agree with experimental results. A high barrier was found near pseudorotation angle P = TI, where no sugar in crystal form has been observed. The barrier along the pseudorotation path 1-,as about 3.37 Kcal/mole. The key interactions causing the high TT barrier were between the base N and endocyclic atoms across the ring, and between the backbone C and endocyclic atoms across the ring. Also the two H's in~ positions with respect to the ring 0 played a key role in the high 1r barrier. In the deoxyribose analog, the +gauche conformation for the hydroxyl had a slightly lower energy than -gauche or trans. For the B conformation of the ribonucleic acid sugar analog two global minima were found. The two minima were separated by a high barrier (2.65 Kcal/ mole) near P = TI and a low barrier (0.46 Kcal/mole) near P = 0. This also seemed to be consistent with experimental X-ray crystallography and nuclear magnetic resonance solution results. Key interactions for the high TI barrier were the same as for the deoxyribose analog. For the two hydroxyls of the ribose analog a -gauche, +gauche conformation was predicted to be favored.

Degree Name

Physics

Level of Degree

Doctoral

Department Name

Physics & Astronomy

First Committee Member (Chair)

Charles Leroy Beckel

Second Committee Member

Robert Edwin Tapscott

Third Committee Member

M. J. Benson

Fourth Committee Member

Howard Carnes Bryant

Language

English

Document Type

Dissertation

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