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.

Energy Cascades, Excited State Dynamics, and Photochemistry in Cob(III)alamins and Ferric Porphyrins

“…In particular, a blue shift of the αβ band reflects changes in the axial bonds in the electronic excited states. In what follows, we will compare state-of-the-art TD-DFT quantum chemical calculations, ,− ,− with experimental measurements for several cob­(III)­alamins.…”

“…8,9 Alkylcobalamins possess a unique carbon−cobalt bond capable of thermal and photolytic cleavage producing a range of reactive organic ions and radicals. 10−14 Potential applications of cobalamins include spatiotemporal control of drug delivery through C−Co bond cleavage 15,16 and optically controlled formation of OH radicals throuch O−Co bond cleavage. 17 These applications complement the range of applications proposed for metalloporphyrins.…”

“…The interest in metallocorrins as photoactivated agents has developed somewhat slower than porphyrins, but applications are now appearing. Cobalamin is a cobalt–corrin compound incorporated as an alkyl derivative into a variety of enzymes including two human enzymes. , Alkylcobalamins possess a unique carbon–cobalt bond capable of thermal and photolytic cleavage producing a range of reactive organic ions and radicals. − Potential applications of cobalamins include spatiotemporal control of drug delivery through C–Co bond cleavage , and optically controlled formation of OH radicals throuch O–Co bond cleavage . These applications complement the range of applications proposed for metalloporphyrins.…”

Ligand-Tuning of the Stability of Pd(II) Conjugates with Cyanocobalamin

“…The core of the corrin ring stripped of the peripheral groups, was used as a geometric model of the macrocyclic ligand in CblCN in which the dimethylbenzimidazole was replaced by an imidazole molecule. Such a model of cobalamin was already used in earlier studies and proved to yield reliable results [ 45 , 46 , 47 ]. For the conjugate 1 two different isomers were considered: cis - and trans - in respect to the location of the chloride ligand in the Pd(II) coordination sphere.…”