title: DNA interaction studies and evaluation of biological activity of homo- and hetero-trihalide mononuclear Cu(II) Schiff base complexes. Quantitative structure-activity relationships.
abstract: A new series of mixed-ligand mono- or hetero-trihalide Cu(II) complexes of the type [Cu(dienXX)Y(YZ(2))], where dienXX=Schiff dibase of diethylenetriamine with 2-thiophene-carboxaldehyde (dienSS), 2-furaldehyde (dienOO) or 2-pyrrole-2-carboxaldehyde (dienNN), Y=Cl, Br and Z=Br, I was synthesized by the reaction of the precursors of the type [Cu(dienXX)Y]Y with iodine or bromine in 1:1 molar ratio. The distorted square pyramidal configuration of the new homo- and hetero-trihalide Cu(II) mononuclear complexes was identified by C, H, N, Cu analysis, spectroscopic methods (IR, UV-visible), molar conductivity and magnetic measurements. The basal plane consists of three nitrogen atoms of the Schiff base and one halogen (terminal) atom while another axially located trihalogen moiety occupies the fifth side of the square pyramid as a YZ(2) entity, adopting an almost linear configuration. The equilibrium geometry of these complexes was further corroborated by theoretical studies at the B3LYP/DGDZVP level. A series of quantum chemical descriptors (e.g. SOMO (singly occupied molecular orbital) LUMO (lowest occupied molecular orbital), SOMO and LUMO energies, SOMO-LUMO gap, dipole moment, polarizability, molar volume, etc.) have been utilized in order to deduce quantitative structure-activity relationships (QSARs). The effect of the new compounds on the single stranded (ss), double stranded (ds) and pDNA led either to the formation of a DNA-complex cationic adduct, or to its degradation, evidenced by DNA electrophoretic mobility and DNA interaction spectroscopic titration studies. Moreover, the antimicrobial activity of Cu(II) complexes against Gram(+) and Gram(-) bacteria can be attributed to the synergistic action of the dissociation species, namely the cationic [Cu(dienXX)Y](+) and anionic [YZ(2)](-) ones. Finally, de Novo linear regression analysis correlating the bioactivity of these complexes with their structural substituents has been carried out, leading to some interesting qualitative observations/conclusions.
authors.affiliation: Department of Chemistry, Laboratory of Inorganic Chemistry, Aristotle University of Thessaloniki, 541 24 Thessaloniki, Greece.
authors.forename: A T
authors.initials: AT
authors.lastname: Chaviara
authors.forename: E E
authors.initials: EE
authors.lastname: Kioseoglou
authors.forename: A A
authors.initials: AA
authors.lastname: Pantazaki
authors.forename: A C
authors.initials: AC
authors.lastname: Tsipis
authors.forename: P A
authors.initials: PA
authors.lastname: Karipidis
authors.forename: D A
authors.initials: DA
authors.lastname: Kyriakidis
authors.forename: C A
authors.initials: CA
authors.lastname: Bolos
mesh_terms: D001965:Bromides / Q000737:chemistry; D002712:Chlorides / Q000737:chemistry; D003300:Copper / Q000737:chemistry* / Q000378:metabolism; D004247:DNA / Q000378:metabolism*; D006090:Gram-Negative Bacteria / Q000187:drug effects / Q000254:growth & development; D006094:Gram-Positive Bacteria / Q000187:drug effects / Q000254:growth & development; D016014:Linear Models; D009682:Magnetic Resonance Spectroscopy; D008826:Microbial Sensitivity Tests; D009942:Organometallic Compounds / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D021281:Quantitative Structure-Activity Relationship; D012545:Schiff Bases / Q000737:chemistry*; D013055:Spectrophotometry, Infrared; D013056:Spectrophotometry, Ultraviolet
chemical_list: D001965:Bromides; D002712:Chlorides; D009942:Organometallic Compounds; D012545:Schiff Bases; D003300:Copper; D004247:DNA