Ionization energies of metallocenes: a coupled cluster study of cobaltocene.

Open-shell transition metal chemistry presents challenges to contemporary electronic structure methods, based on either density functional or wavefunction theory. While CCSD(T) is the well-trusted gold standard for maingroup thermochemistry, the accuracy and robustness of the method is less clear for open-shell transition metal chemistry, requiring benchmarking of CCSD(T)-based protocols against either higher-level theory or experiment. Ionization energies (IEs) of metallocenes provide an interesting test case with metallocenes being common redox reagents as well as playing roles as redox mediators and cocatalysts in redox catalysis. Using highly accurate ZEKE-MATI experimental measurements of gas phase adiabatic (5.3275 ± 0.0006 eV) and vertical (5.4424 ± 0.0006 eV) ionization energies of cobaltocene, we systematically assessed the accuracy of the local coupled-cluster method DLPNO-CCSD(T) with respect to geometry, reference determinant, basis set size and extrapolation schemes, PNO cut-off and extrapolation, local triples approximation, relativistic effects and core-valence correlation. We show that PNO errors are controllable via the recently introduced PNO extrapolation schemes and that the expensive iterative triples (T1) contribution can be made more manageable by calculating it as a smaller-basis/smaller PNO-cutoff correction. The reference determinant turns out to be a critical aspect in these calculations with the HF determinant resulting in large DLPNO-CCSD(T) errors, likely due to the qualitatively flawed molecular orbital spectrum. The BP86 functional on the other hand was found to provide reference orbitals giving small DLPNO-CCSD(T) errors, likely due to more realistic orbitals as suggested by the more consistent MO spectrum compared to HF. A protocol including complete basis set extrapolations with correlation-consistent basis sets, complete PNO space extrapolations, iterative triples- and core-valence correlation corrections was found to give errors of -0.07 eV and -0.03 eV for adiabatic- and vertical-IE of cobaltocene, respectively, giving close to chemical accuracy for both properties. A computationally efficient DLPNO-CCSD(T) protocol was devised and tested against adiabatic ionization energies of 6 different metallocenes (V, Cr, Mn, Fe, Co, Ni). For the other metallocenes, the iterative triples (T1) and PNO extrapolation contributions turn out to be even more important. The results give errors close to the experimental uncertainty, similar to recent auxiliary-field quantum Monte Carlo results. The quality of the reference determinant orbitals is identified as the main source of uncertainty in CCSD(T) calculations of metallocenes.

Evaluation of cobalt complexes with tripod ligands for zinc finger targeting.

Cobalt complexes have been demonstrated to target zinc fingers, as shown by investigations of Doxovir, the trade name of the [CoIII(acacen)(2-Me-Imz)2]+ drug in clinical trials. Mechanistic studies indicate zinc finger disruption by metal coordination to His residues. Other than Doxovir, a few studies have investigated other ligands and geometries for cobalt complexes for zinc finger targeting. Tripod ligands demonstrated good zinc and cobalt chelation. In this manuscript, we report the ability of CoII and CoIII complexes of tri(2-pyridylmethyl)amine and N,N-di(2-pyridylmethyl)glycinate to disrupt zinc fingers. The results obtained by mass spectrometry and X-ray absorption spectroscopy demonstrate that the complexes were able to remove zinc from the zinc fingers. The product was oxidised apo-peptide. In contrast, the ligands themselves were able to remove zinc, and they did not promote oxidation, resulting in free Cys residues. Cobalt finger adducts were not detected for the complexes with tripod ligands unless they were coordinated to planar ligands such as salen or acacen. Studies of the interactions of cobalt complexes with amino acids demonstrated that tripod ligands promote the cysteine reaction, while the salen ligands promote histidine coordination, demonstrating a different mechanism of action. The results reported here are significant for better understanding and further design of zinc finger targeting compounds.

The influence of ZnII coordination sphere and chemical structure over the reactivity of metallo-ß-lactamase model compounds.

A systematic study of the influence of the first coordination sphere over the reactivity and structure of metallo-ß-lactamase (MßL) monozinc model complexes is reported. Three ZnII complexes with tripodal ligands forming the series [Zn(N-NNN)], [Zn(N-NNS)], and [Zn(N-NNO)] where N-NNX represents the tripodal donor atoms were investigated regarding their ability to mimic MßL. The tripodal series was inspired by MßL active sites in the respective subclasses, representing the (His, His, His) Zn1 site present in B1 and B3 subclasses, (His, His, Asp) present in the B3 subclass site and the thiolate present in B1 and B2 sites. The results were supported by electronic structure calculations. XAS analysis demonstrated that the ZnII electronic deficiency significantly changes in the order [Zn(N-NNS)] < [Zn(N-NNN)] < [Zn(N-NNO)]. This effect directly affects the reactivity over nitrocefin and amoxicillin, observed by the hydrolysis kinetics, which follows the same trend. NMR spectroscopy revealed the coordination of the carboxylic group in the substrate to the metal changes accordingly, affecting the hydrolysis kinetics. Our results also demonstrated that not only the Lewis acidity is changed by the ligand system but also the softness of the metal. [Zn(N-NNS)] is softened by the thiolate, promoting the ligand substitution reaction with solvents and favoring a secondary interaction with substrates, not observed for [Zn(N-NNO)]. XRD of the models reveals their similar geometric aspects in comparison to the crystal structure of GOB MßL. The present work demonstrates that the ZnII electronic details must be considered in the design of new MßL models that will further aid in the design of clinically useful inhibitors.