Synthesis, Characterization, and Reactivity of Urea Derivatives Coordinated to Cobalt(III). Possible Relevance to Urease

Abstract

The syntheses of a cobalt(III) complex, 2, containing N-(2-pyridylmethyl)urea and of six complexes, 3, containing phenyl-substituted N-2-pyridylmethyl-N'-(X)phenylureas (where X = 4-H, 4-CH(3), 4-Br, 3-Cl, 4-CF(3), and 4-NO(2)), have been accomplished by reaction of [(en)(2)Co(OSO(2)CF(3))(2)](CF(3)SO(3)) with the urea ligands in tetramethylene sulfone. The complexes have been characterized by UV-vis, FTIR, (1)H NMR, and (13)C NMR spectra along with elemental analysis. Also, X-ray crystallographic analysis of 2 confirms that the urea ligand chelates as a bidentate through the pyridyl nitrogen atom and the endo deprotonated, urea nitrogen atom to form a stable five-membered ring. Crystals of the perchlorate salt of 2 were monoclinic, space group P2(1)/c with a = 9.743(1) Å, b = 13.924(3) Å, c = 15.006(4) Å, beta = 97.07(1) degrees, and Z = 4. Reflection data (3454) with I = 3sigma(I) were refined to conventional R factors of 0.037 and 0.051. In acidic solution (0.05-1.00 M HCl at 55 degrees C), the phenyl-substituted complexes undergo hydrolysis to form the bis(ethylenediamine)(2-picolylamine-N,N')cobalt(III) ion, 4, aniline, and CO(2). The hydrolysis kinetics of the phenyl-substituted complexes were studied by UV-vis spectroscopy (I = 1.00 M HCl/LiCl). At 55 degrees C the observed rate constants fit the rate law k(obsd) = kK[H(+)]/(1 + K[H(+)]). It is proposed that the protonated urea eliminates aniline to give a coordinated isocyanate intermediate that hydrolyzes rapidly to the pyridyl methylamine complex and CO(2) via the carbamate complex. Since all of the studies of this kind to date appear to involve the NCO intermediate, it raises the prospect that urease also functions by a similar path and that urease should be tested with NCO(-) as a substrate.

Enzymatic Catalysis of Urea Decomposition: Elimination or Hydrolysis?

“…26 To mimic the active-site chemistry of urease, several molecular model systems have been synthesized, which were designed to evaluate the possible binding modes of urea as well as to carry out hydrolytic transformations at dinuclear nickel(II) cores that mimic the urease active site. [27][28][29][30][31][32][33][34][35][36][37][38][39][40] The bidentate coordination of urea has been supported, in part, by the isolation of complexes such as [L 2 Ni 2 (m-OAc)-(urea)](ClO 4 ) 2 (L ) pyrazolate derivative), where hydrogen bonding by the NH 2 groups to an oxygen atom of a bridging carboxylate was confirmed by structural analyses. 34 Further structural confirmation of urea bidentate coordination has been derived from the crystallographic analysis of triazacyclononane (TACN)/ pyrazolate hybrid complexes.…”

Synthetic Models for the Active Sites of Nickel‐Containing Enzymes

“…It implies that urea fi rst coordinates to both nickel ions in a N,O bridging mode, followed by nucleophilic attack by the bridging hydroxide. However, details of this process, including the mode of urea binding and the exact identity of the nucleophile, are still under debate, and cyanate has also been proposed as a possible intermediate in the urease mechanism [148]. The very slow, uncatalyzed decomposition of urea gives ammonia and cyanic acid with a half life of 3.6 yr at 38ЊC in the pH range 2-12 [149][150][151].…”

Reaction of 2-Pyridylmethylthiourea Derivatives with [(en)2Co(OSO2CF3)2]+ Induces Hypodentate Coordination of an Ethylenediamine Ligand

“…1) with [(en) 2 Co (OSO 2 CF 3 ) 2 ] þ in tetramethylene sulfone. Substituted thiourea ligands that do not contain a pyridyl group coordinate to the [(en) 2 Co] 3þ subunit in a bidentate manner through the thiourea sulfur atom and a deprotonated nitrogen atom (Fig. 2), [1] while the urea analogues of the ligands illustrated in Fig.…”

“…3). [2] Our original intent in pursuing this work was to prepare the thiourea analogues of the complex illustrated in Fig. 3 to complement our previous study on the acid hydrolysis of the urea analogues.…”

“…3 to complement our previous study on the acid hydrolysis of the urea analogues. [2] While each of the previously studied ligands afforded relatively simple chemistry when reacted with the cobalt precursor-forming predominately two structural isomers upon reaction with non-pyridylcontaining thiourea ligands or the desired urea complex upon reaction with pyridyl urea ligands-reaction with pyridylcontaining thiourea ligands was complicated by the unexpected cleavage of a single Co-N(en) bond in the usually robust [(en) 2 Co] 3þ fragment, which facilitated tridentate coordination of the hybrid ligand (Fig. 4d) in up to 55 % yield.…”