title: Exploring novel modified vitamin B12 as a drug carrier: forecast from density functional theory modeling.
abstract: Three non-native derivatives of vitamin B12 with imidazole, ethylenediamine, and pyrazine as cobalt(III) β-ligands were characterized by applying the BP/def2-TZVP density functional method. The binding of all three ligands is thermodynamically favorable. It is proposed that their synthesis might be possible from aquacobalamin as a starting form of vitamin B12, as has been done in the case of an imidazole derivative of B12 (Hannibal et al. Inorg. Chem. 2007, 46, 3613-3618). Furthermore, the possibility of the formation of their conjugates with cisplatin is investigated. The proposed β-ligands may serve as bridging ligands, binding to the platin ion as N-donors. In parallel, the calculations are done for the previously synthetized B12-cisplatin adduct with CN(-) as a bridging ligand and are compared with available experimental data, allowing assessment of the applied computational protocol. A good agreement between the computed and experimental structural parameters is obtained. In each of the studied structures, the Co-β-ligand bond is weaker than the Pt-β-ligand bond.
authors.affiliation: Jerzy Haber Institute of Catalysis and Surface Chemistry, Polish Academy of Sciences, Kraków, Poland. nczbik@cyf-kr.edu.pl
authors.forename: Dorota
authors.initials: D
authors.lastname: Rutkowska-Zbik
authors.forename: Gabriela
authors.initials: G
authors.lastname: Mazur
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Drzewiecka-Matuszek
authors.forename: Łukasz
authors.initials: Ł
authors.lastname: Orzeł
authors.forename: Grażyna
authors.initials: G
authors.lastname: Stochel
mesh_terms: D002945:Cisplatin / Q000737:chemistry; D003035:Cobalt / Q000737:chemistry; D056831:Coordination Complexes / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry*; D005029:Ethylenediamines / Q000737:chemistry; D007093:Imidazoles / Q000737:chemistry; D008024:Ligands; D008962:Models, Theoretical; D011719:Pyrazines / Q000737:chemistry; D014805:Vitamin B 12 / Q000031:analogs & derivatives / Q000737:chemistry*
chemical_list: D056831:Coordination Complexes; D004337:Drug Carriers; D005029:Ethylenediamines; D007093:Imidazoles; D008024:Ligands; D011719:Pyrazines; C043960:aquacobalamin; D003035:Cobalt; C031234:ethylenediamine; C029899:imidazole; D014805:Vitamin B 12; D002945:Cisplatin