Exploring the limits of nucleobase expansion: computational design of naphthohomologated (xx-) purines and comparison to the natural and xDNA purines

The properties of doubly-expanded (xx-) purine analogues are compared to the natural and singly-expanded (x-) purines using quantum chemical (B3LYP, MP2) methods. Purine expansion upon incorporation of a benzene or naphthalene spacer affects the preferred orientation of the base about the glycosidic...

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Bibliographic Details
Published in:Physical chemistry chemical physics : PCCP 2013-10, Vol.15 (37), p.15538-15549
Main Authors: SHARMA, Purshotam, LAIT, Linda A, WETMORE, Stacey D
Format: Article
Language:English
Subjects:
Base Pairing
Benzene Derivatives - chemistry
Bonding
Chemistry
DNA - chemistry
Exact sciences and technology
General and physical chemistry
Hydrogen Bonding
Models, Molecular
Naphthalene
Naphthalenes - chemistry
Nucleic Acid Conformation
Nucleosides
Purines
Purines - chemistry
Quantum chemistry
Spacers
Stability
Stacking
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Summary:The properties of doubly-expanded (xx-) purine analogues are compared to the natural and singly-expanded (x-) purines using quantum chemical (B3LYP, MP2) methods. Purine expansion upon incorporation of a benzene or naphthalene spacer affects the preferred orientation of the base about the glycosidic bond in the corresponding nucleoside to a similar extent. Although the natural purines preferentially adopt the anti orientation with respect to the 2'-deoxyribose moiety, the syn and anti conformations are almost isoenergetic in the case of the expanded analogues. However, the anti/syn rotational barrier either remains similar to or is slightly elevated upon purine expansion, and therefore the expanded analogues will likely display similar rigidity with respect to rotation about the glycosidic bond as the natural purines. The A:T Watson-Crick hydrogen-bond strength is slightly enhanced, while the G:C interaction energy decreases slightly, upon incorporation of either expanded purine. As expected, the largest effect of base expansion occurs on the stacking energies. Specifically, the maximum (most negative) stacking energies in isolated purine dimers formed by aligning the nucleobase centers of mass can be increased by up to 34% by including a single x-purine and by up to 51% by including an xx-purine. Although increases in the purinepurine intrastrand stacking interactions are found even when a simplified duplex model composed of two stacked (hydrogen-bonded) base pairs is considered, the purinepyrimidine stacking energies decrease upon purine expansion. However, the total stability (sum of all hydrogen-bonding and stacking interactions) of natural duplex models is up to 10% and 22% greater for duplexes containing expanded x- and xx-purines respectively, which is mainly due to enhanced inter and intrastrand stacking interactions. Thus, unidirectional expansion in the size of the nucleobase spacer can continuously enhance the stability of expanded duplexes.
ISSN:1463-9076
1463-9084
DOI:10.1039/c3cp52656a