Sristi Raj Rai, Amity University Kolkata
To feel the protein environment working and its dynamic nature, one needs to collect as much information possible about the acidic/basic residues which make them. A group of enzyme proteins called metalloenzymes has these residues present within the secondary coordination sphere of their active site. Synthetic modelling of acidic groups into a pre-arranged secondary sphere can provide us with an understanding of the part they are playing in substrate binding.
However, it is still tough to capture the mobility-dependent in such rigid molecular scaffold modelling. Therefore, to resolve this issue, John J. Kiernicki et al. designed a flexible model by using a variable spacer length of the ligand appended lewis acid (BBN) attached to series of transition metal complexes [(n-BBNNNtBu)ZnBr2 where n=2,3,4].
The solid-state data suggests a slight difference between the binding pockets of the series. Spectroscopy showed that the system is suitable for distance-dependent cooperative study (carried out using hydrazine – N2H4 as a substrate) as the distance between the two acidic centres Zn and B increases by 1 Å (approx.) with increasing –(CH2)n– units. SC-XRD studies after halide abstraction from the complexes [(n-BBNNNtBu)ZnBr2(N2H4)] formed by lone pair acceptor – Lewis acid and hydrazine, resulted in [(n-BBNNNtBu)ZnBr(N2H4)][X] complex (where X = OTf, PF6). Overall results indicate a significant increase in the bond distance between Zn-N2H4 with increasing n value, adding to spring like the flexibility to the acidic group and making it suitable for the substrate binding.
Without the lewis acid-binding of N2H4, the demethylation of the ligand will take place. Kinetically, the tether length affects the rate of on/off binding inversely. They are further exploring how to ideally manipulate the tether length to perfectly fit other given substrates and efficiently utilize the 3 C tether to stabilize various other high-energy reduction products from a single substrate.
Also read: Use of semi-permeable capsules in multi-step processing of single cells
REFERENCE – Kiernicki, J., Norwine, E., Lovasz, M., Zeller, M. and Szymczak, N., 2020. Mobility of Lewis acids within the secondary coordination sphere: toward a model for cooperative substrate binding.
Chemical Communications. https://pubs.rsc.org/en/content/articlelanding/2020/cc/d0cc05121g#!divAbstract
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