Characterization of Cobalt(III) Hydroxamic Acid Complexes Based on a Tris(2-pyridylmethyl)amine Scaffold: Reactivity toward Cysteine Methyl Ester

Six Co­(III) complexes based on unsubstituted or substituted
TPA
ligands (where TPA is tris­(2-pyridylmethyl)­amine) and acetohydroxamic
acid (A), N-methyl-acetohydroxamic acid
(B), or N-hydroxy-pyridinone (C) were prepared and characterized by mass spectrometry, elemental
analysis, and electrochemistry: [Co­(III)­(TPA)­(A-2H)]­(Cl) (1a), [Co­(III)­((4-Cl2)­TPA)­(A-2H)]­(Cl) (2a),
[Co­(III)­((6-Piva)­TPA)­(A-2H)]­(Cl) (3a), [Co­(III)­((4-Piva)­TPA)­(A-2H)]­(Cl)
(4a) and [Co­(III)­(TPA)­(B–H)]­(Cl)2 (1b), and [Co­(III)­(TPA)­(C–H)]­(Cl)2 (1c). Complexes 1a–c and 3a were analyzed by 1H NMR, using 2D (1H, 1H) COSY and 2D (1H, 13C) HMBC
and HSQC, and shown to exist as a mixture of two geometric isomers
based on whether the hydroxamic oxygen was trans to
a pyridine nitrogen or to the tertiary amine nitrogen. Complex 3a exists as a single isomer that was crystallized. Its crystal
structure revealed the presence of an H-bond between the pivaloylamide
and the hydroximate oxygen. Complexes 1a, 2a, and 4a are irreversibly reduced beyond −900
mV versus SCE, while complexes 1b and 1c are reduced at less negative values of −330 and −190
mV, respectively. The H-bond in 3a increased the redox
potential up to −720 mV. Reaction of complex 1a with l-cysteine methyl ester CysOMe was monitored by 1H NMR and UV–vis at 2 mM and 0.2 mM in an aqueous buffered
solution at pH 7.5. Complex 1a was successively converted
into an intermediate [Co­(III)­(TPA)­(CysOMe-H)]2+, 1d, by exchange of the hydroximate with the cysteinate ligand,
and further into Co­(III)­(CysOMe-H)3, 5. An
authentic sample of 1d was prepared and thoroughly characterized.
A detailed 1H NMR analysis showed there was only one isomer,
in which the thiolate was trans to the tertiary amine
nitrogen.