Tuning the redox potentials of ternary cobalt(III) complexes containing various hydroxamates

Abstract

Sixteen cobalt(III) complexes incorporating one of the investigated 4N donor tripodal amines in the presence or absence of differently substituted hydroxamates have been synthesized and the effect of the nature of the N-donor, size of the chelates formed and the effect of the type of the substituent(s) at the hydroxamate moiety on the redox properties of the complexes have been studied. The crystal and molecular structures of the new complexes, [Co(unspenp)(H 2 O)Cl]Cl 2 .H 2 O (4), [Co(tren)(phebha)](ClO 4 ) 2 (11), [Co(tpa)(bha)](ClO 4 ) 2 •C 2 H 5 OH•H 2 O (15) and [Co(tpa)(phebha)](ClO 4 ) 2 ( 16) have also been determined by single crystal X-ray diffraction method. Cyclic voltammetric (CV) results indicated the irreversible reduction of Co(III) in all the investigated complexes. Out of the four studied tripodal amines, abap was found to decrease the Co(III/II) reduction potential far below the region of bioreductants. Decreasing of two of the chains by one CH 2 in tren compared to abap resulted in less negative reduction potential of the corresponding complex.Further positive shift was observed by introducing two (uns-penp), and especially three (tpa)π-back-bonding pyridyl rings into the chains of tetramines. In agreement with literature results, the 3+ oxidation state of the central cobalt ion was found to be extremely stabilized in the ternary complexes containing the doubly deprotonated benzohydroximate, but the metal ion is significantly more reducible in the ternary complexes with mono-deprotonated benzohydroxamate/derivative ligands. Measurable effect was not found on the redox potential via introduction of chloro or nitro substituents in para position into the phenyl moiety of bha -(Cl-bhaand NO 2 -bha -). Significant positive shift (ca. 200 mV) was obtained, however, when R N = H was replaced by a phenyl ring in phebhatherefore complexes with this latter ligand can be likely candidates for the in vitro releasing of hydroxamates with proven biological activity.

Pd(II) Binding Strength of a Novel Ambidentate Dipeptide-Hydroxypyridinonate Ligand: A Solution Equilibrium Study

“…K 2 [PdCl 4 ] (Sigma-Aldrich) was used for preparing the Pd(II) stock solutions by dissolving it in doubly deionized and ultrafiltered water from a Milli-Q RG (Millipore) water purification system and by adding a known amount of HCl to avoid hydrolysis. [Co(tren)Cl 2 ]Cl was synthesized as previously reported [ 13 ].…”

“…Various types of Pd(II) complexes themselves exhibit remarkable anticancer potential sometimes via a different mechanism of action compared to the platinum(II) analogues [ 8 , 9 , 10 , 11 ]. Rationally tailored redox properties of the above type Co(III) complexes enable selective reduction in Co(III) to Co(II) under the hypoxic environment of the cancer cells only [ 12 , 13 , 14 ]. As a consequence, the free (O,O) chelating groups can exert their biological effects after the dissociation of the Co(II) complex having lower thermodynamic stability and faster ligand exchange properties compared to those of the parent complex.…”

Harnessing the properties of cobalt coordination complexes for biological application

“…(c) a citotoxidade apenas das espécies reduzidas. A faixa de potencial de redução ideal sugerida para o ambiente de hipóxia é de -400 a -200 mV vs EPH [9,34], embora alguns trabalhos considerem uma faixa um pouco maior de -500 a -100 mV vs EPH, para que o prófármaco seja ativado por flavoproteínas [25,35,36]. Desta forma, a eficiência de um prófármaco biorredutível é dependente, também, do seu potencial redox, de modo que geralmente são feitas correlações entre a atividade e o comportamento eletroquímico [31,37].…”

“…A literatura consultada sugere que o potencial de redução de HL (-1,82 V vs Fc/Fc + e - Em termos da elaboração de um pró-fármaco biorredutível, um dos parâmetros avaliados é a faixa do potencial de redução em que a molécula se tornará ativa. Para ativação em hipóxia, a faixa ideal reportada na literatura é geralmente de -0,4 a -0,2 V vs EPH [9,34] ou, por alguns autores, de -0,5 a -0,1 V vs EPH [25,35,36]. Complexos contendo ligantes marcadores fluorescentesderivados de cumarina e antraquinonaforam reportados como modelos de pró-fármacos, apresentando potenciais de redução dentro da faixa ideal, -0,387 e -0,250 V vs EPH, em DMF [36].…”

Donor Atom Preference of Organoruthenium and Organorhodium Cations on the Interaction with Novel Ambidentate (N,N) and (O,O) Chelating Ligands in Aqueous Solution

“…Hypoxia present in cancer tissues is a remarkable difference from normoxic conditions in healthy, untransformed cells enabling the development of metal complexes that are selectively activated under hypoxic conditions. Due to the large difference, in general, in the stability and in the rate of ligand exchange reactions, cobalt complexes can be promising candidates for selective hypoxia-activation [6][7][8][9][10]. The inert Co(III) form can act namely as a chaperon carrying a biologically active ligand, and in the more reductive environment of the cancer tissue via selective reduction and subsequent dissociation of the Co(II) species formed, targeted release of the active biomolecule can be achieved.…”