An Experimental and Computational Analysis on the Differential Role of the Positional Isomers of Symmetric Bis-2-(pyridyl)-1H-benzimidazoles as DNA Binding Agents

Chaudhuri, Padmaparna and Ganguly, Bishwajit and Bhattacharya, Santanu (2007) An Experimental and Computational Analysis on the Differential Role of the Positional Isomers of Symmetric Bis-2-(pyridyl)-1H-benzimidazoles as DNA Binding Agents. In: Journal of Organic Chemistry, 72 (6). pp. 1912-1923.

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Abstract

Three symmetrical positional isomers of bis-2-(n-pyridyl)-1H-benzimidazoles (n = 2, 3, 4) were synthesized and DNA binding studies were performed with these isomeric derivatives. Like bisbenzimidazole compound Hoechst 33258, these molecules also demonstrate AT-specific DNA binding. The binding affinities of 3-pyridine (m-pyben) and 4-pyridine (p-pyben) derivatized bisbenzimidazoles to doublestranded DNA were significantly higher compared to 2-pyridine derivatized benzimidazole o-pyben. This has been established by combined experimental results of isothermal fluorescence titration, circular dichroism, and thermal denaturation of DNA. To rationalize the origin of their differential binding characteristics with double-stranded DNA, computational structural analyses of the uncomplexed ligands were performed using ab initio/Density Functional Theory. The molecular conformations of the symmetric head-to-head bisbenzimidazoles have been computed. The existence of intramolecular hydrogen bonding was established in o-pyben, which confers a conformational rigidity to the molecule about the bond connecting the pyridine and benzimidazole units. This might cause reduction in its binding affinity to double-stranded DNA compared to its para and meta counterparts. Additionally, the predicted stable conformations for p-, m-, and o-pyben at the B3LYP/6-31G* and RHF/6-31G* levels were further supported by experimental $pK_a$ determination. The results provide important information on the molecular recognition process of such symmetric head to head bisbenzimidazoles toward duplex DNA.

Item Type:	Journal Article
Publication:	Journal of Organic Chemistry
Publisher:	American Chemical Society
Additional Information:	Copyright of this article belongs to American Chemical Society.
Department/Centre:	Division of Chemical Sciences > Organic Chemistry
Date Deposited:	02 Jun 2008
Last Modified:	19 Sep 2010 04:45
URI:	http://eprints.iisc.ac.in/id/eprint/14109

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