Chemical Modification Strategies for Enhanced Urease Inhibition Activity: Coordination Polymer Optimization Techniques
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Abstract
The development of effective urease inhibitors has emerged as a critical research frontier in combating urease-related pathologies and agricultural challenges. This comprehensive study explores advanced chemical modification strategies for enhancing urease inhibition activity through systematic coordination polymer optimization techniques. The research investigates the structural-activity relationships of metal-organic coordination polymers, focusing on ligand design, metal center selection, and synthetic optimization approaches. Through systematic analysis of coordination environments and their impact on enzyme inhibition mechanisms, this work demonstrates significant improvements in urease inhibition efficacy. The study encompasses detailed examinations of copper-based, manganese-based, and mixed-metal coordination polymers, revealing that strategic chemical modifications can enhance inhibition activity by up to 300% compared to conventional inhibitors. Advanced characterization techniques including X-ray crystallography, spectroscopic analysis, and molecular docking studies provide mechanistic insights into the inhibition processes. The optimization strategies focus on chelation enhancement, dimensional control, and auxiliary ligand incorporation, demonstrating remarkable potential for therapeutic applications against Helicobacter pylori infections and agricultural urease management. These findings establish a comprehensive framework for rational design of next-generation urease inhibitors with superior selectivity and reduced toxicity profiles.
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1. H. Yu, Z. Li, W. Wang, C. Wei, L. Liu, and C. Liu et al., "Application of nanoscale metal-organic coordination polymers in cancer therapy," Chem. Eng. J., vol. 496, p. 154342, 2024, doi: 10.1016/j.cej.2024.154342.
2. P. Kafarski and M. Talma, "Recent advances in design of new urease inhibitors: A review," J. Adv. Res., vol. 13, pp. 101–112, 2018, doi: 10.1016/j.jare.2018.01.007.
3. Y. Zhai, J. Li, S. Shen, Z. Zhu, S. Mao, X. Xiao, C. Zhu, J. Tang, X. Lu, and J. Chen, “Recent advances on dual‐band electrochromic materials and devices,” Adv. Funct. Mater., vol. 32, no. 17, p. 2109848, 2022, doi: 10.1002/adfm.202109848.
4. G. Xie, W. Guo, Z. Fang, Z. Duan, X. Lang, D. Liu, G. Mei, Y. Zhai, X. Sun, and X. Lu, “Dual‐Metal Sites Drive Tandem Electrocatalytic CO2 to C2+ Products,” Angew. Chem., vol. 136, no. 47, p. e202412568, 2024, doi: 10.1002/ange.202412568.
5. G. Mei, Z. Sun, Z. Fang, Y. Dan, X. Lu, J. Tang, W. Guo, Y. Zhai, and Z. Zhu, “CoNi alloy nanoparticles encapsulated within N-doped carbon nanotubes for efficiently pH-universal CO₂ electroreduction,” Small, vol. 21, no. 31, p. 2504086, 2025, doi: 10.1002/smll.202504086.
6. M. Guo, K. Liu, K. Wang, J. Liu, P. Wang, F. Zhao, X. Zhang, and L. Zhang, “Sacrificial doping of interstitial lithium facilitated undoped amorphous/crystalline RuO₂ toward boosted acidic water oxidation,” Adv. Energy Mater., p. e03199, 2025, doi: 10.1002/aenm.202503199.
7. L. Hu, R. Li, C. Chen, X. Jia, X. Li, L. Jiao, C. Zhu, X. Lu, Y. Zhai, and S. Guo, “Cu single sites on BO₂ as thyroid peroxidase mimicking for iodotyrosine coupling and pharmaceutical assess,” Sci. Bull., 2025, doi: 10.1016/j.scib.2025.03.010.
8. S. Kunkalienkar, N. S. Gandhi, A. Gupta, M. Saha, A. Pai, and S. Shetty, "Targeting Urease: A Promising Adjuvant Strategy for Effective Helicobacter pylori Eradication," ACS Omega, vol. 10, no. 27, pp. 28643–28669, 2025, doi: 10.1021/acsomega.5c02725.
9. C. Almarmouri, M. I. El-Gamal, M. Haider, M. Hamad, Shamsul Qumar, and M. Sebastian et al., "Anti-urease therapy: a targeted approach to mitigating antibiotic resistance in Helicobacter pylori while preserving the gut microflora," Gut Pathog., vol. 17, no. 1, 2025, doi: 10.1186/s13099-025-00708-1.
10. F. Ding, C. Y. Hung, J. K. Whalen, L. Wang, Z. Wei, L. Zhang, and Y. Shi, "Potential of chemical stabilizers to prolong urease inhibition in the soil–plant system," J. Plant Nutr. Soil Sci., vol. 185, no. 3, pp. 384–390, 2022, doi: 10.1002/jpln.202100314.
11. F. Ding, C. Ma, W.-L. Duan, and J. Luan, "Second auxiliary ligand induced two coppor-based coordination polymers and urease inhibition activity," J. Solid State Chem., vol. 331, pp. 124537–124537, 2023, doi: 10.1016/j.jssc.2023.124537.
12. A. V. Gurbanov, Fateme Firoozbakht, Nafiseh Pourshirband, Paria Sharafi-Badr, Payam Hayati, and B. Souri et al., "A new 1D Mn (II) coordination polymer: Synthesis, crystal structure, hirshfeld surface analysis and molecular docking studies," Heliyon, vol. 10, no. 8, pp. e29565–e29565, 2024, doi: 10.1016/j.heliyon.2024.e29565.
13. G. I. Dzhardimalieva and I. E. Uflyand, "Design and synthesis of coordination polymers with chelated units and their application in nanomaterials science," RSC Adv., vol. 7, no. 67, pp. 42242–42288, 2017, doi: 10.1039/c7ra05302a.
14. E. R. Engel and J. L. Scott, "Advances in the green chemistry of coordination polymer materials," Green Chem., vol. 22, 2020, doi: 10.1039/d0gc01074j.
15. P. Giri, A. D. Pagar, M. D. Patil, and H. Yun, "Chemical modification of enzymes to improve biocatalytic performance," Biotechnol. Adv., vol. 53, p. 107868, 2021, doi: 10.1016/j.biotechadv.2021.107868.
16. S. Del Prete and M. Pagano, "Enzyme Inhibitors as Multifaceted Tools in Medicine and Agriculture," Molecules, vol. 29, no. 18, p. 4314, 2024, doi: 10.3390/molecules29184314.
17. F. Ding, N. Su, C. Ma, B. Li, W.-L. Duan, and J. Luan, "Fabrication of two novel two-dimensional copper-based coordination polymers regulated by the 'V'-shaped second auxiliary ligands as high-efficiency urease inhibitors," Inorg. Chem. Commun., vol. 170, p. 113319, 2024, doi: 10.1016/j.inoche.2024.113319.
18. Y. Duan, D. Chen, R. Zhang, Y. Du, and L. Wang, "Optimizing the coordination environment of active sites to enhance heterogeneous electrocatalytic performances," Coord. Chem. Rev., vol. 522, p. 216243, 2024, doi: 10.1016/j.ccr.2024.216243.
19. S. W. Jaros, J. Sokolnicki, Miłosz Siczek, and Piotr Smoleński, "Strategy for an Effective Eco-Optimized Design of Heteroleptic Cu(I) Coordination Polymers Exhibiting Thermally Activated Delayed Fluorescence," Inorg. Chem., 2023, doi: 10.1021/acs.inorgchem.3c01908.