Theoretical insights into the mechanism of carbon monoxide (CO) release from CO-releasing molecules |
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Authors: | Vummaleti Sai Vikrama Chaitanya Branduardi Davide Masetti Matteo De Vivo Marco Motterlini Roberto Cavalli Andrea |
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Affiliation: | Department of Drug Discovery and Development, Istituto Italiano di Tecnologia via Morego 30, 16163 Genova, Italy. |
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Abstract: | We used density functional theory to investigate the capacity for carbon monoxide (CO) release of five newly synthesized manganese-containing CO-releasing molecules (CO-RMs), namely CORM-368 (1), CORM-401 (2), CORM-371 (3), CORM-409 (4), and CORM-313 (5). The results correctly discriminated good CO releasers (1 and 2) from a compound unable to release CO (5). The predicted Mn-CO bond dissociation energies were well correlated (R(2) ≈0.9) with myoglobin (Mb) assay experiments, which quantified the formation of MbCO, and thus the amount of CO released by the CO-RMs. The nature of the Mn-CO bond was characterized by natural bond orbital (NBO) analysis. This allowed us to identify the key donor-acceptor interactions in the CO-RMs, and to evaluate the Mn-CO bond stabilization energies. According to the NBO calculations, the charge transfer is the major source of Mn-CO bond stabilization for this series. On the basis of the nature of the experimental buffers, we then analyzed the nucleophilic attack of putative ligands (L' = HPO(4)(2-), H(2)PO(4)(-), H(2)O, and Cl(-)) at the metal vacant site through the ligand-exchange reaction energies. The analysis revealed that different L'-exchange reactions were spontaneous in all the CO-RMs. Finally, the calculated second dissociation energies could explain the stoichiometry obtained with the Mb assay experiments. |
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