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Abstract Metal–ligand bonding and noncovalent interactions (NCIs), such as hydrogen bonding orπ–πinteractions, play a crucial role in determining the structure, function, and selectivity of both biological and artificial metalloproteins. In this study, we employed a hybrid quantum mechanics/molecular mechanics (QM/MM) approach to investigate the ligation of water or cyanide in a mutated myoglobin system, in which the native heme scaffold was replaced with M-salophen or M-salen Schiff base complexes (M = Cr, Mn, Fe). Using our local vibrational mode analysis, particularly local vibrational mode force constants as intrinsic bond strength parameters, complemented with electron density and natural orbital analyses we explored the role of metal–ligand bonding and NCIs in different environments within the myoglobin pocket. Our analysis revealed that metal–ligand bonding, for both water and cyanide ligands, is strongest in the delta form of distal histidine and favors salophen prosthetic groups, as indicated by an overall increase in metal–ligand bond strength. Hydrogen bonding between the distal histidine and ligand also exhibited greater strength in the delta form; however, this effect was more pronounced with salen prosthetic groups. Additionally, the NCIs within the active pocket of the protein were found to be variable, highlighting the adaptability of local force constants. In summary, our data underscore the potential of computational methodologies in guiding the rational design of artificial metalloproteins for tailored applications, with local vibrational mode analysis serving as a powerful tool for bond strength assessment.
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Weak and strong π interactions between two monomers—assessed with local vibrational mode theory
We introduce in this work a unique parameter for the quantitative assessment of the intrinsic strength of the π interaction between two monomers forming a complex. The new parameter is a local intermonomer stretching force constant, based on the local mode theory, originally developed by Konkoli and Cremer, and derived from the set of nine possible intermonomer normal vibrational modes. The new local force constant was applied to a diverse set of more than 70 molecular complexes, which was divided into four groups. Group 1 includes atoms, ions, and small molecules interacting with benzene and substituted benzenes. Group 2 includes transition metal hydrides and oxides interacting with benzene while Group 3 involves ferrocenes, chromocenes, and titanium sandwich compounds. Group 4 presents an extension to oxygen π–hole interactions in comparison with in-plane hydrogen bonding. We found that the strength of the π interactions in these diverse molecular complexes can vary from weak interactions with predominantly electrostatic character, found, e.g., for argon–benzene complexes, to strong interactions with a substantial covalent nature, found, e.g., for ferrocenes; all being seamlessly described and compared with the new intermonomer local mode force constant, which also outperforms other descriptors such as an averaged force constant or a force constant guided by the electron density bond paths. We hope that our findings will inspire the community to apply the new parameter also to other intermonomer π interactions, enriching in this way the broad field of organometallic chemistry with a new efficient assessment tool.
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- Award ID(s):
- 2102461
- PAR ID:
- 10430209
- Date Published:
- Journal Name:
- Canadian Journal of Chemistry
- ISSN:
- 0008-4042
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1139/cjc-2022-0254
