Fabrication of two 5-R-isophthalic acid-modulated Cu-based coordination polymers as urease inhibitors

Abstract

Urease is an enzyme that catalyzes the hydrolysis of urea to ammonia and carbon dioxide. Accordingly, the addition of urease inhibitors can delay the hydrolysis of urea, and thus improve the fertilizer efficiency. Herein, a new N-donor ligand, 5-hydroxy-N¹,N³-di(pyridin-3-yl)isophthalamide, was synthesized and combined with different types of acids to prepare two Cu-based coordination polymers (Cu-CPs), namely, [Cu(3-dpip)(1,3,5-HBTC)] (Cu-CP-COOH) and [Cu₂(3-dpip)(5-NIP)₂(H₂O)₂] (Cu-CP-NO₂), where 1,3,5-H₃BTC = 1,3,5-benzenetricarboxylic acid and 5-H₂NIP = 5-nitroisophthalic acid, which served as urease inhibitors (UIs) and showed excellent inhibition with IC₅₀ values of 1.60 ± 0.01 μM for Cu-CP-COOH and 1.24 ± 0.01 μM for Cu-CP-NO₂. The role of Cu-CP-COOH and Cu-CP-NO₂ in the kinetics of urease inhibition was also investigated and the Lineweaver–Burk (L–B) curves indicated that both inhibitors were anti-competitive inhibitors. A virtual screen for urease showed binding energies of −10.28 kcal mol⁻¹ for Cu-CP-COOH and −11.34 kcal mol⁻¹ for Cu-CP-NO₂. More importantly, 5-R-isophthalic acid (R = –COOH and –NO₂) played an important role in urease inhibition activity. The structure–function relationship was further discussed, which indicates that Cu-CPs can be used as a type of UI.