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Hydrolysis of the Amide Bond in L-Methionine- and L-Histidine-Containing Dipeptides in the Presence of Dinuclear Palladium(II) Complexes with Benzodiazines Bridging Ligands

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Abstract

1H NMR spectroscopy was applied to study the catalytic activity of dinuclear Pd(II)-aqua complexes with different benzodiazine bridging ligands, [{Pd(en)(H2O)}2(μ-qx)]4+ (Pd1), [{Pd(en)(H2O)}2(μ-qz)]4+ (Pd2) and [{Pd(en)(H2O)}2(μ-phtz)]4+ (Pd3) (qx, qz and phtz denote quinoxaline, quinazoline and phthalazine, respectively), in the hydrolytic cleavage of the amide bond in N-acetylated L-methionylglycine (Ac–L–Met–Gly) and L-histidylglycine (Ac–L–His–Gly) dipeptides. All reactions were investigated with an equimolar amount of the reactants at pH = 2.0–2.5 in D2O and at 37 °C. The obtained data for the catalytic activity of Pd1–Pd3 complexes are compared with those previously reported for [{Pt(en)(H2O)}2(μ-L)]4+ (L denotes benzodiazine: qx, qz and phtz), [{Pd(en)(H2O)}2(μ-L)]4+ and [{Pt(en)(H2O)}2(μ-L)]4+ (L denotes diazine: pyrazine and pyridazine) complexes. It was found that catalytic activity of these complexes in peptide cleavage is strongly related to the position of the nitrogen atoms in the benzodiazine or diazine bridging ligand. The investigated dinuclear Pd(II) and Pt(II) complexes show catalytic activity in the selective hydrolysis of the Met–Gly amide bond of Ac–L–Met–Gly dipeptide. Moreover, all the above mentioned Pd(II) complexes were also able to catalyze the regioselective hydrolysis of the His–Gly amide bond of Ac–L–His–Gly dipeptide. However, in the reaction with Ac–L–His–Gly, only Pt(II) aqua complexes containing bridging ligands with two nitrogen atoms in the para-position (quinoxaline and pyrazine) were able to cleave this dipeptide.

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Acknowledgements

This work was funded in part by the Ministry of Education, Science and Technological Development of the Republic of Serbia (Agreement No. 451-03-68/2020-14/200122) and the Serbian Academy of Sciences and Arts (Strategic projects program-Grant agreement No. 01-2019-F65 and Project No. F128).

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Authors and Affiliations

  1. University of Kragujevac, Faculty of Medical Sciences, Department of Pharmacy, Svetozara Markovića 69, 34000, Kragujevac, Serbia

    Marija D. Živković

  2. University of Kragujevac, Faculty of Science, Department of Chemistry, Radoja Domanovića 12, 34000, Kragujevac, Serbia

    Andjela A. Franich & Snežana Rajković

  3. University of Kragujevac, Institute for Information Technologies Kragujevac, Department of Science, Jovana Cvijića bb, 34000, Kragujevac, Serbia

    Darko P. Ašanin

  4. University of Priština, Faculty of Agriculture, Kopaonička bb, 38228, Lešak, Serbia

    Nenad S. Drašković

  5. Serbian Academy of Sciences and Arts, Knez Mihailova 35, 11000, Belgrade, Serbia

    Miloš I. Djuran

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  1. Marija D. Živković
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  2. Andjela A. Franich
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Correspondence to Marija D. Živković.

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10953_2020_1012_MOESM1_ESM.doc

Supplementary information associated with this article includes NMR (1H and 13C) spectra of dinuclear Pd1-Pd3 complexes and Figs. S1 and S2. (DOC 1399 kb)

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Živković, M.D., Franich, A.A., Ašanin, D.P. et al. Hydrolysis of the Amide Bond in L-Methionine- and L-Histidine-Containing Dipeptides in the Presence of Dinuclear Palladium(II) Complexes with Benzodiazines Bridging Ligands. J Solution Chem 49, 1082–1093 (2020). https://doi.org/10.1007/s10953-020-01012-z

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