The influence of Zn^II coordination sphere and chemical structure over the reactivity of metallo-β-lactamase model compounds

Abstract

The first coordination sphere influences the reactivity of metallo-β-lactamase monozinc model complexes.

Zinc pyrithione is a potent inhibitor of PLPro and cathepsin L enzymes with ex vivo inhibition of SARS-CoV-2 entry and replication

“…An interesting study discussing the influence of zinc coordination sphere on the reactivity of the metal centre showed, that certain type of a ligand affects Lewis acidity as well as hard/soft character of the zinc. In particular, thiolate ligands soften the zinc core and enable more interactions with functional groups such as amines or amides 70 , which are present also in the catalytic triade of the cathepsin L (Cys138–His276–Asn300) 71 and PL Pro (Cys111, His272, and Asp286) 72 . It is worth noting that Wang et al.…”

A multiscale approach to predict the binding mode of metallo beta‐lactamase inhibitors

“…Indeed, lower RMSD values were generally obtained using a rigid binding pocket (Opt2, Opt4), and these further improved (for six out of nine thiolate ligands) when PLANTS was used with crystallographic water molecules added to the binding pocket (Opt3). This highlights the important role of interactions involving the water network in the binding sites of ligands 62–64 . However, with one exception (PDB id: 2DOO 60 ), improvement was generally not observed when AutoDock Vina was used with water molecules included.…”

Following a Silent Metal Ion: A Combined X-ray Absorption and Nuclear Magnetic Resonance Spectroscopic Study of the Zn2+ Cation Dissipative Translocation between Two Different Ligands

“… 20 , 36 − 38 Moreover, the presence of pre-edge features were observed in Zn 2+ complexes with tripodal ligands and was attributed to a MLCT excitation into low lying pyridine π* orbitals. 39 Finally, the experimental XAS spectrum of 1 •Zn 2+ shows the presence of a shoulder at the rising edge (transition A, Figure 2 c) that has been assigned to a dipole allowed 1s to 4p transition. 20 …”

“…9659.9 eV (transition A, inset of Figure d) which is absent in the spectrum of 1 •Zn 2+ (see inset of Figure c). It is well-known that pre-edge features predominantly occur because of a 1s to 3d transition, and should therefore not be theoretically possible in metals with filled 3d orbitals such as Zn 2+ . , However, pre-edges have been observed in other nominally d 10 metal complexes, such as Cu + complexes, − and explained as resulting from metal-to-ligand charge transfer (MLCT). ,− Moreover, the presence of pre-edge features were observed in Zn 2+ complexes with tripodal ligands and was attributed to a MLCT excitation into low lying pyridine π* orbitals . Finally, the experimental XAS spectrum of 1 •Zn 2+ shows the presence of a shoulder at the rising edge (transition A, Figure c) that has been assigned to a dipole allowed 1s to 4p transition …”