Abstract
199mHg PAC and 199Hg NMR spectroscopic properties, nuclear quadrupole coupling
constants, Q, asymmetry parameters, , and chemical shifts, , respectively, are the fingerprint of the local molecular and electronic structure, at the probed Hg nuclei. For this reason, these spectroscopic techniques have been used to elucidate Hg coordination in proteins. Computational chemistry calculations have a potential to contribute to the interpretation of this spectroscopic data, as calculated diagonalised electric field gradient (EFG) tensor components (jVzzj jVyyj jVxxj) and NMR shielding constants, , can be related to Q, and values. The aim of this study was to lay the foundation for the future interpretation of 199mHg PAC and 199Hg NMR spectroscopic data in proteins using a computational chemistry approach.
In this respect, in Paper 1 - 3 and in Section 6.4 we estimated the size of electron correlation effects, relativistic effects and the coupling between them for V zz, and values in some small Hg compounds and concluded that it is important to take into account these effects on an equal footing. Furthermore,
we found Density Functional Theory (DFT) functionals which could reproduce
computationally demanding Coupled Cluster results. We also determined to what
degree the computationally cheaper approximate relativistic methods ZORA(-4) and SR-ZORA-4 at the DFT level can reproduce fully-relativistic results. As a result, we proposed reliable computational methods applicable to Hg binding sites in proteins:
• ZORA-4/BH&H for 199mHg PAC spectroscopic properties,
• ZORA/BH&HLYP for 199Hg NMR spectroscopic properties.
By using these methods we further examined in Section 6.5 the influence of the
immediate crystal environment on these spectroscopic properties and concluded that it does matter, in some cases more than in others. These results suggest that the calculations on the Hg binding sites in proteins should include the immediate
chemical environment. In addition, for the first time in Paper 2 we conducted the projection analysis of molecular orbital contributions to Vzz in some small Hg
compounds in terms of the atomic constituents. The analysis provided a chemophysical interpretation of changes in Vzz upon structural distortions and ligand
exchange. The gained insights can be useful when predicting and understanding
changes in Q values for Hg binding sites in proteins.
One of the first steps towards understanding how Zn(II) reaches its target position
in biological systems in vivo and in vitro experiments in aqueous solution, is the detailed investigation of water exchange reactions for Zn(II)(aq). A very advanced
(albeit not complete) picture of structure and dynamics of solvated Zn(II) ion has been provided by experiments. It suggests the 1st coordination sphere of Zn(II) comprising six water molecules, the dissociative-interchange water exchange
mechanism between the 1st and 2nd coordination spheres and water exchange rates 3 107 s􀀀1 < kH2O < 6 108 s􀀀1. However, these studies did not provide the insight into the microscopic nature of the water exchange mechanism. The aim of this study was to provide this insight using a computational chemistry approach.
In this respect, in our work presented in Section 6.6 we first equilibrated the Zn(II) + 64 H2O system using a Car-Parrinello molecular dynamics approach(CPMD) and showed that the 1st coordination sphere of Zn(II) comprises six water molecules in agreement with the experimental results. Secondly, we performed Direct CPMD metadynamics simulations on the equilibrated structure by introducing an additional bias potential acting on two collective variables describing the coordination of Zn(II). The simulations proposed the insight into the microscopic nature of the dissociative water exchange mechanism, nevertheless, it needs further validation.
constants, Q, asymmetry parameters, , and chemical shifts, , respectively, are the fingerprint of the local molecular and electronic structure, at the probed Hg nuclei. For this reason, these spectroscopic techniques have been used to elucidate Hg coordination in proteins. Computational chemistry calculations have a potential to contribute to the interpretation of this spectroscopic data, as calculated diagonalised electric field gradient (EFG) tensor components (jVzzj jVyyj jVxxj) and NMR shielding constants, , can be related to Q, and values. The aim of this study was to lay the foundation for the future interpretation of 199mHg PAC and 199Hg NMR spectroscopic data in proteins using a computational chemistry approach.
In this respect, in Paper 1 - 3 and in Section 6.4 we estimated the size of electron correlation effects, relativistic effects and the coupling between them for V zz, and values in some small Hg compounds and concluded that it is important to take into account these effects on an equal footing. Furthermore,
we found Density Functional Theory (DFT) functionals which could reproduce
computationally demanding Coupled Cluster results. We also determined to what
degree the computationally cheaper approximate relativistic methods ZORA(-4) and SR-ZORA-4 at the DFT level can reproduce fully-relativistic results. As a result, we proposed reliable computational methods applicable to Hg binding sites in proteins:
• ZORA-4/BH&H for 199mHg PAC spectroscopic properties,
• ZORA/BH&HLYP for 199Hg NMR spectroscopic properties.
By using these methods we further examined in Section 6.5 the influence of the
immediate crystal environment on these spectroscopic properties and concluded that it does matter, in some cases more than in others. These results suggest that the calculations on the Hg binding sites in proteins should include the immediate
chemical environment. In addition, for the first time in Paper 2 we conducted the projection analysis of molecular orbital contributions to Vzz in some small Hg
compounds in terms of the atomic constituents. The analysis provided a chemophysical interpretation of changes in Vzz upon structural distortions and ligand
exchange. The gained insights can be useful when predicting and understanding
changes in Q values for Hg binding sites in proteins.
One of the first steps towards understanding how Zn(II) reaches its target position
in biological systems in vivo and in vitro experiments in aqueous solution, is the detailed investigation of water exchange reactions for Zn(II)(aq). A very advanced
(albeit not complete) picture of structure and dynamics of solvated Zn(II) ion has been provided by experiments. It suggests the 1st coordination sphere of Zn(II) comprising six water molecules, the dissociative-interchange water exchange
mechanism between the 1st and 2nd coordination spheres and water exchange rates 3 107 s􀀀1 < kH2O < 6 108 s􀀀1. However, these studies did not provide the insight into the microscopic nature of the water exchange mechanism. The aim of this study was to provide this insight using a computational chemistry approach.
In this respect, in our work presented in Section 6.6 we first equilibrated the Zn(II) + 64 H2O system using a Car-Parrinello molecular dynamics approach(CPMD) and showed that the 1st coordination sphere of Zn(II) comprises six water molecules in agreement with the experimental results. Secondly, we performed Direct CPMD metadynamics simulations on the equilibrated structure by introducing an additional bias potential acting on two collective variables describing the coordination of Zn(II). The simulations proposed the insight into the microscopic nature of the dissociative water exchange mechanism, nevertheless, it needs further validation.
| Originalsprog | Engelsk |
|---|
| Forlag | Department of Chemistry, Faculty of Science, University of Copenhagen |
|---|---|
| Antal sider | 149 |
| Status | Udgivet - 2013 |