Optimization of Reaction Parameters for the Synthesis of Chromium Methionine Complex Using Response Surface Methodology

Tris-asparaginatochromium(III), [Cr(Asn)3]0 (where Asn forms a 5-membered chelate ring via amine nitrogen and α-carboxylate oxygen atoms) and its mono- and diaqua-derivatives were obtained, and their acid-catalyzed aquation was studied. The first reaction for [Cr(Asn)3]0 and [Cr(Asn)2(H2O)2]+ is the chelate ring opening at the Cr-NH2 bond, leading to metastable intermediates. Kinetics of these processes were studied spectrophotometrically in 0.1–1.0 M HClO4 at 303 and 333 K, respectively. A linear dependence of kobs on [H+], kobs = a + b[H+] was determined for both the complexes. Additionally, oxidation of chromium(III) to chromate(VI) by hydrogen peroxide was studied. The process proceeds through a chromium(V) intermediate, which is next transformed, in faster parallel steps into CrO42− and [Cr(O2)2]3− anions. The latter species, a chromium(V)-peroxo complex, is metastable under a large excess of H2O2. Kinetics of oxidation of [Cr(Asn)3]0 were studied at 298 K, at constant [OH−], within 0.2–1.0 M H2O2 range. A linear dependence of kobs on H2O2 was established. A mechanism is proposed, where the rate-determining step is an inner sphere 2-electron transfer within a precursor chromium(III) complex with coordinated O2H− anion of the [Cr(Asn)2(OH)(HO2)]− formula. EPR results provided clear evidence for formation of a relatively stable tetrakis(η2-peroxo)chromate(V) complex, [Cr(O2)4]3−.

Kinetic studies on H+-catalyzed aquation and hydrogen peroxide oxidation of tris-asparaginatochromium(III)

A potential synthetic biochromium source, bis-aspartatochromium(III) ion (where Asp is a tridentate N,O,O′-ligand, bonded via amine nitrogen and carboxylate oxygen atoms) has been obtained and characterized in aqueous solution. Kinetics of partial dechelation of the complex catalysed by H+ and OH− ions has been studied spectrophotometrically within 0.1–1.0 M HClO4 and 0.1–1.0 M NaOH ranges under first-order conditions. A linear dependence of the k
 obs,H on [H+] and independence of the k
 obs,OH on [OH−] were established. The derived rate expression and identification of components of the reaction mixture provide evidence for a reaction mechanism, where the key role in the overall process is the formation of an intermediate species with bidentate N,O-bonded Asp via both spontaneous and H+(OH−)-catalysed reaction paths. The intermediate is meta-stable and at pH 5–7 restores the substrate.

Kinetic studies on H + - and OH − -catalysed aquation of bis -aspartatochromium(III)

Two chromium(III)–cysteine complexes, [Cr(Cys)2]− and [Cr(Cys)(H2O)3]+, have been synthesized, and their reactivity in aqueous solution studied. Kinetics of the acid-catalyzed Cr–S bond fission was studied in strongly acidic medium, monitoring the absorbance decrease of the S → Cr CT band. The dependences of the pseudo-first-order rate constants on [H+] were determined. The spontaneous Cr–S bond cleavage in [Cr(Cys)2]− was studied in alkaline medium monitoring the spectral changes within the d–d transition bands. Based on the obtained kinetic and spectroscopic data, a reaction mechanism is proposed and factors controlling the rate of Cr–S cleavage are discussed.

Hydrolytic chromium(III)–sulfur bond cleavage in chromium(III)–cysteine complexes

Synthesis, spectroscopic characterization, and theoretical studies on the substitution reaction of chromium(III) picolinate

Three chromium(III) complexes with asparagine (Asn) and histidine (His) of the [Cr(ox)2(Aa)]2− type, where Aa = N,O–Asn, N,O–His or N,N′–His, were obtained and characterized in solution. The complexes with N,O–Aa undergo acid-catalysed aquation to give a free amino acid and cis-[Cr(ox)2(H2O)2]−, whereas the complex with N,N′–His undergoes parallel reaction paths: (1) isomerization to the N,O–His complex and (2) liberation of an oxalate ligand. Kinetics of the N,O–Aa complexes in HClO4 media were studied spectrophotometrically under pseudo-first-order conditions. The absorbance changes were attributed to the chelate ring opening at the Cr–N bond. The linear dependence of rate constants on [H+] was established, and a mechanism for the chelate ring cleavage was postulated. The existence of a metastable intermediate with O-monodentate Aa ligand was proved experimentally. Effect of [Cr(ox)2(Aa)]2− on 3T3 fibroblasts proliferation was studied. The tests revealed low cytotoxicity of the complexes. Complexes with Ala, His and Cys are good candidates for biochromium sources.

Kinetic studies on H+-catalysed aquation of chromium(III)-oxalato-asparaginato and chromium(III)-oxalato-histidinato complexes

Partial dechelation of one tridentate N,N′,O-histidine in trans-imidazole-[Cr(His)2]+ (where N and N′ are amine and imidazole nitrogen atoms, respectively, and O is carboxylate oxygen) has been studied. The aquation process is both acid and base catalyzed and the product with didentate His is converted back into the substrate at pH 4–7. Kinetics of the chelate ring opening were studied spectrophotometrically within the 0.01–1.0 M HClO4 and 0.1–1.0 M NaOH ranges under first-order conditions. The following dependences of k obs on [H+] and [OH−] were determined:

$$ \left( {k_{\text{obs}} } \right)_{\text{H}} = a + b\left[ {{\text{H}}^{ + } } \right] + c/\left[ {{\text{H}}^{ + } } \right] $$



$$ \left( {k_{\text{obs}} } \right)_{\text{OH}} = a^{\prime } + b^{\prime } \left[ {{\text{OH}}^{ - } } \right]. $$

Mechanisms of the chelate ring opening in acidic and alkaline media are proposed, and activation parameters for the process in acidic solution have been determined. Additionally, kinetic studies were performed on the second dechelation stage in acidic media, which is ca. 15 times slower than the first one.

Sylwia Kuchta

Papers

Kinetic studies on H+-catalysed aquation of chromium(III)-oxalato-asparaginato and chromium(III)-oxalato-histidinato complexes

Kinetic studies on pH controlled partial dechelation of the trans-imidazole-[Cr(His)2]+ cation