title: Intrinsic conformational preferences of the Hoechst dye family and their influence of DNA binding.
abstract: Quantum mechanical calculations have been used to investigate the molecular conformation of the Hoechst family of DNA-binding dyestuffs. Compounds in which the phenolic substituent adopts either a meta or para position were studied. Two different environments have been considered, which are the gas phase and aqueous solution; the conformation in aqueous solution has been modeled through a self-consistent reaction field strategy. The results clearly indicate that Hoechst dyes do not adopt a planar conformation and that the degree of planarity is controlled by the external environment. A comparison with experimental data reveals that the conformation of Hoechst dyes in the gas phase is similar to that observed in DNA complexes by X-ray crystallography. In aqueous solution, the conformation deviates from planarity more than in the gas phase, since non-bonded interactions with the solvent offset the loss of conjugative interactions. The role of the drug conformation in the binding mechanism with DNA is discussed.
authors.affiliation: Department de Biologia Molecular i Cellular, Centre d'Investigació i Desenvolupament, Barcelona, Spain.
authors.forename: M C
authors.initials: MC
authors.lastname: Vega
authors.forename: M
authors.initials: M
authors.lastname: Coll
authors.forename: C
authors.initials: C
authors.lastname: Alemán
mesh_terms: D001483:Base Sequence; D001562:Benzimidazoles / Q000737:chemistry; D006690:Bisbenzimidazole / Q000737:chemistry; D004396:Coloring Agents / Q000737:chemistry; D004247:DNA; D004563:Electrochemistry; D005583:Fourier Analysis; D008958:Models, Molecular; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000737:chemistry*; D012996:Solutions; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013816:Thermodynamics
chemical_list: D001562:Benzimidazoles; D004396:Coloring Agents; D009838:Oligodeoxyribonucleotides; D012996:Solutions; D004247:DNA; D006690:Bisbenzimidazole