Noncovalent attachment of psoralen derivatives with DNA: Hartree  /Fock and density functional studies on the probes Tarek M. El-Gogary a, *, Eman M. El-Gendy b a Chemistry Department, Faculty of Science (Domyat), Mansoura University, Domyat AL-Gideda, Egypt b Department of Home Economy, Faculty of Specific Education, Mansoura University, Mansoura, Egypt Received 14 October 2002; received in revised form 13 January 2003; accepted 13 January 2003 Abstract Two psoralen derivatives (probes) were prepared. Their geometries were optimized at the Hartree  /Fock (HF) and Density Functional (B3LYP) levels employing 6-31G** and cc-pVDZ basis sets. Their interaction with DNA was investigated using spectrophotometric and computational techniques. Both of them have shown strong binding to calf thymus DNA. The red-shift and hypochromism that detected in the spectrum were taken as an evidence for the strong interaction between these probes and DNA. The spectrophotometric DNA titration data were treated by two different methodologies to calculate the intercalation affinity. Half-reciprocal plots gave binding constants of 5.5065 /10 4 and 6.4727 /10 4 for 8-butoxypsoralen (8-BOP) and 8-hexoxypsoralen (8-HOP), respectively. Schatchard plots gavea comparable intercalation binding constants and also the surface binding constants along with the number of intercalated probe molecules per base pair. The interaction between these probes and DNA were studied theoretically. The energy of interaction was computed using molecular mechanics method. Strength of interaction of these probes with different types of DNA was computed and compared. Calculated energies of interaction were compared with the observed intercalation affinities. HOMO and LUMO energies were computed and used to account for the strength of interaction. # 2003 Elsevier B.V. All rights reserved. Keywords: Intercalation; Spectrophotometric titration; DNA; Psoralens; Ab initio DFT calculations 1. Introduction Psoralens are naturally occurring and/or syn- thetic substances which are used in treatment of skin diseases. Psoralen derivatives have been used for many years in the experiments of vitiligo and psoriasis [1,2]. Various biological targets are likely to be involved in the therapeutic effects of such compounds. Their anti-proliferative effects are usually related to their ability to undergo photo- cycloaddition reactions with pyrimidine DNA- bases, and particularly with thymine, leading to the formation of monofunctional and bifunctional adducts [3]. Psoralens, as furocoumarin deriva- tives, have been actively investigated with regard * Corresponding author. Tel.:  /20-5743003; fax:  /20- 57403868. E-mail address: tarekelgogary@hotmail.com (T.M. El- Gogary). Spectrochimica Acta Part A 59 (2003) 2635  /2644 www.elsevier.com/locate/saa 1386-1425/03/$ - see front matter # 2003 Elsevier B.V. All rights reserved. doi:10.1016/S1386-1425(03)00038-6