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Interactions of molecules with nucleic acids. V. Intercalation of thioxanthenones into DNA
Author(s) -
Miller Kenneth J.,
Lauer Michael,
Archer Sydney
Publication year - 2009
Publication title -
international journal of quantum chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.484
H-Index - 105
eISSN - 1097-461X
pISSN - 0020-7608
DOI - 10.1002/qua.560180703
Subject(s) - intercalation (chemistry) , chemistry , base pair , chromophore , stereochemistry , dna , crystallography , substituent , molecule , helix (gastropod) , protonation , binding energy , nucleic acid , dimer , photochemistry , inorganic chemistry , organic chemistry , biochemistry , biology , ecology , ion , physics , snail , nuclear physics
Binding positions, conformations, and relative minimum binding energies of thioxanthenones, lucanthone, and N‐methyllucanthone are calculated for intercalation complexes with DNA in the theoretically determined principal intercalation sites I and II. The optimum binding position of thioxanthenone is identical to that for the chromophore in lucanthone and in its N‐methyl derivative. Intercalative binding is optimized in lucanthone and N‐methyllucanthone because the chromophore is not disrupted by substituents, and the amino side chain conforms to the phosphate backbone without an increase in conformational energy over that of the free molecule. N‐methyl substitution of lucanthone results in a reorientation of the NCH 2 ‐CH 2 NH(+)(CH 2 CH 3 ) 2 substituent and a net loss in electrostatic energy resulting in a decrease of 17.9 kcal in the total binding energy. This result is consonant with the experimental observation that N‐methyllucanthone does not intercalate into DNA, whereas lucanthone does. Specificity for base pair sequences in intercalation complexes with lucanthone is attributed primarily to the energy required to open B‐DNA to an intercalation site and secondarily to the orientation of the terminal protonated nitrogen toward the carbonyl oxygen on cytosine. Both of these effects enhance the preference for one base. Because the distribution of base pairs G‐C and A‐T in all 16 dimer duplex intercalation complexes is uniform throughout the range of energy of the complexes, base pair specificity should not be observed for a random distribution of G‐C and A‐T. However, there is a sequence specificity for synthetic DNA in the order of decreased binding: poly(dC)‐poly(dG) > poly(dA‐dT)‐poly(dA‐dT) > poly(dG‐dC)‐poly(dG‐dC) > poly(dA)‐poly(dT).