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.

Switching the Spin-Crossover Phenomenon by Ligand Design on Imidazole-Diazineiron(II) Complexes.

The iron(II) complexes of two structural isomers of 2-(1 H-imidazol-2-yl)diazine reveal how ligand design can be a successful strategy to control the electronic and magnetic properties of complexes by fine-tuning their ligand field. The two isomers only differ in the position of a single diazinic nitrogen atom, having either a pyrazine (Z) or a pyrimidine (M) moiety. However, [Fe(M)3](ClO4)2 is a spin-crossover complex with a spin transition at 241 K, whereas [Fe(Z)3](ClO4)2 has a stable magnetic behavior between 2 and 300 K. This is corroborated by temperature-dependent Mössbauer spectra showing the presence of a quintet and a singlet state in equilibrium. The temperature-dependent single-crystal X-ray diffraction results relate the spin-crossover observed in [Fe(M)3](ClO4)2 to changes in the bond distances and angles of the coordination sphere of iron(II), hinting at a stronger σ donation of ligand Z in comparison to ligand M. The UV/vis spectra of both complexes are solved by means of the multiconfigurational wave-function-based method CASPT2 and confirm their different spin multiplicities at room temperature, as observed in the Mössbauer spectra. Calculations show larger stabilization of the singlet state in [Fe(Z)3]2+ than in [Fe(M)3]2+, stemming from the slightly stronger ligand field of the former (506 cm-1 in the singlet). This relatively weak effect is indeed capable of changing the spin multiplicity of the complexes and causes the appearance of the spin transition in the M complex.