title: A combined semiempirical and DFT computational protocol for studying bioorganometallic complexes: application to molybdocene-cysteine complexes.
abstract: Computational methods can help in the design of new bioorganometallic compounds. However, the presence of multihapto or σ/π metal-ligand bonding still precludes the direct application of either pure molecular mechanics (MM) or hybrid quantum mechanics-MM methods to study the flexibility of biomolecules in complex with organometallics. Herein, we present a computational protocol aimed to the evaluation of the relative free energies of bioorganometallic compounds, which explores the conformational space by means of Molecular Dynamics simulations using the semiempirical PM6 method coupled with the COnductor-like Screening MOdel solvation model followed by density functional theory (DFT) calculations including the DFT-D3 dispersion energy correction on the most stable conformers. This protocol is applied to investigate the complexes formed between cysteine and the molybdocene entity Cp2Mo(2+) (Cp=η(5)-C5H5), which has received considerable attention due to its potential antitumor activity and chemical reactivity. The calculated structures and free energies are in agreement with those of the experimentally detected molybdocene-cysteine adducts and allow us to investigate the reaction mechanism for the formation of the most stable 1:1 and 1:2 adducts.
authors.affiliation: Departamento de Química Física y Analítica, Facultad de Química, Universidad de Oviedo, C/ Julián Clavería 8, Oviedo, 33006, Spain.
authors.forename: Dimas
authors.initials: D
authors.lastname: Suárez
authors.forename: Natalia
authors.initials: N
authors.lastname: Díaz
authors.forename: Ramón
authors.initials: R
authors.lastname: López
mesh_terms: D003545:Cysteine / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D008968:Molecular Conformation; D009942:Organometallic Compounds / Q000737:chemistry*; D011789:Quantum Theory
chemical_list: D009942:Organometallic Compounds; D003545:Cysteine
keywords: conformational search • semiempirical calculations • density functional calculations • bioorganometallic complexes • molybdocene