Structure and properties of the 5a,6-anhydrotetracycline-platinum(II) dichloride complex: a theoretical ab initio study.
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.
Dos Santos
Hélio F
HF
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
Marcial
Bruna L
BL
De Miranda
Carolina F
CF
Costa
Luiz Antônio S
LA
De Almeida
Wagner B
WB
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
D002712:Chlorides; D008024:Ligands; D017671:Platinum Compounds; D013754:Tetracyclines; C016229:4-epianhydrotetracycline; D002945:Cisplatin