Hydrolysis of Dipeptides Catalyzed by a Zirconium(IV)‐Substituted Lindqvist Type Polyoxometalate

Abstract

The hydrolysis of a series of unactivated dipeptides in the presence of a zirconium(IV)‐substituted Lindqvist type polyoxometalate, (Me4N)2[W5O18Zr(H2O)3] (designated as ZrW5), was studied by kinetic experiments and NMR spectroscopy. Among the dipeptides examined, those with the X–Ser amino acid sequence were most effectively hydrolyzed. The kinetics of the hydrolysis of histidylserine (His–Ser) was studied in detail; a rate constant of 95.3 (± 0.1) × 10–7 s–1 (pD 7.4 and 60 °C) in the presence of an equimolar amount of ZrW5 was calculated. The binding of His–Ser to ZrW5 was examined by UV/Vis, 1H, 13C, and 183W NMR spectroscopy, and the data indicate that at physiological pD His–Ser chelates the ZrIV through its imidazole nitrogen, amine nitrogen, and amide carbonyl oxygen. In the presence of ZrW5, the pD profile of kobs is bell‐shaped, with a maximum reaction rate at pD 7.5. At high pD values an inactive complex is formed as a result of the deprotonation of the amide nitrogen, resulting in inhibition of His–Ser hydrolysis. The effects of pH, temperature, inhibitors, and ionic strength on the hydrolysis rate constant were also investigated, and a full account of the mechanism of this novel reaction is given.

Spectroscopic Study of the Interaction between Horse Heart Myoglobin and Zirconium(IV)‐Substituted Polyoxometalates as Artificial Proteases

“…The UV/Vis absorption spectra of 1:1 Zr IV ‐Lindqvist POM in the absence and presence of HHM in acetate buffer at pH 5.0 are presented in Figure S6 in the Supporting Information. The 1:1 Zr IV ‐Lindqvist POM is characterized by an absorption band at λ =265 nm . Figure S6 in the Supporting Information shows that, under the conditions pertinent for HHM hydrolysis, the band at λ =265 nm, corresponding to the Zr‐Lindqvist POM, does not shift to different frequencies; this indicates that the POM remains unchanged in the absence and presence of HHM after several days at 60 °C.…”

Metal assisted peptide bond hydrolysis: Chemistry, biotechnology and toxicological implications

“…The acceleration factor ranges from 2.3 for Zr(IV)-substituted Lindqvist type polyoxymetalates (Zr(IV)-Ld POMs) to 36 for Ce(IV)-substituted Keggin type polyoxymetalates (Ce(IV)-Kg POMs) [18][19][20]23,24,[27][28][29]31,32]. For Ser-Gly the intermolecular attack of the hydroxyl group on the carbonyl carbon would require the formation of an unfavorable four-membered ring.…”

“…The Zr(IV)-assisted hydrolysis by 1:1 Zr(IV)-Ld POM was slower than that observed for 1:2 Zr(IV)-WD POM or the Zr(IV) complex of 4,13-diaza-18-crown-6 (by 2 and 20 times, respectively, for Gly-Ser). The hydrolysis in the presence of 1:1 Zr(IV)-Ld POM combines two features which are desirable from the application point of view: the homogenous nature of the reaction mixture (no precipitation) and the highest reaction yield at physiological pH [29].…”

Hydrolysis of chemically distinct sites of human serum albumin by polyoxometalate: A hybrid QM/MM (ONIOM) study

“…However, currently only a few metal complexes can efficiently catalyze peptide hydrolysis in a regioselective manner under mild conditions . For instance, aqueous solutions of Zr(IV) form precipitates and inactive gels at neutral and basic pH values . Conversely, POMs have been reported to selectively catalyze hydrolysis of a wide range of critical biomolecules such as human serum albumin (HSA), hen egg‐white lysozyme (HEWL), myoglobin, insulin chain B and cytochrome c .…”