title: Structure and properties of the 5a,6-anhydrotetracycline-platinum(II) dichloride complex: a theoretical ab initio study.
abstract: Ab initio structural parameters, relative energies and spectroscopic properties are reported for the 5a,6-anhydrotetracycline-platinum(II) dichloride complex. Distinct coordination modes were analyzed in gas phase and aqueous medium indicating the tricarbonylmethane moiety (O3-Oam-O1) as the most probable Pt(II) complexation sites, supporting experimental proposals. The theoretical (1)H NMR analysis in conjunction with the observed data suggests that the Pt(II) might be bound to the O3-Oam preferentially, even though this site was found slightly unfavorable, based on energetic grounds, relative to O1-Oam. The aquation reaction, which is an important activation step in the action mechanism of cisplatin like molecules, was also investigated showing rate constants (0.5-1 x 10(-5) M(-1) s(-1)) of the same order of magnitude as those for the parent cisplatin compound. This is an important result stressing the importance of tetracyclines-Pt(II) complexes as lead compounds for the development of new platinum based antitumor drugs.
authors.affiliation: NEQC: Núcleo de Estudos em Química Computacional, Departamento de Química--ICE, Universidade Federal de Juiz de Fora, Campus Universitário Martelos, Juiz de Fora, Minas Gerais 36036-900, Brazil. helius@quimica.ufjf.br
authors.forename: Hélio F
authors.initials: HF
authors.lastname: Dos Santos
authors.forename: Bruna L
authors.initials: BL
authors.lastname: Marcial
authors.forename: Carolina F
authors.initials: CF
authors.lastname: De Miranda
authors.forename: Luiz Antônio S
authors.initials: LA
authors.lastname: Costa
authors.forename: Wagner B
authors.initials: WB
authors.lastname: De Almeida
mesh_terms: D002712:Chlorides / Q000737:chemistry; D002945:Cisplatin / Q000031:analogs & derivatives; D007700:Kinetics; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D017671:Platinum Compounds / Q000737:chemistry*; D013754:Tetracyclines / Q000737:chemistry*; D013816:Thermodynamics
chemical_list: D002712:Chlorides; D008024:Ligands; D017671:Platinum Compounds; D013754:Tetracyclines; C016229:4-epianhydrotetracycline; D002945:Cisplatin