Copper(II)-Catalyzed Transamination of Hydrophobic Pyridoxamine with Pyruvic Acid in Functionalized Bilayer Vesicles

Abstract

The copper(II)-catalyzed transamination of 2-methyl-3-hydroxy-4-aminomethyl-5-(dodecylthiomethyl)pyridine (C12SPM) with sodium pyruvate was investigated in an aqueous medium at pH 6.8, μ 0.10 (KCl), and 30.0±0.1 °C in the presence of molecular aggregates of N,N-ditetradecyl-Nα-[6-(trimethylammonio)hexanoyl]-l-alaninamide bromide (N+C5Ala2C14), N,N-ditetradecyl-Nα-[6-(trimethylammonio)hexanoyl]-l-histidinamide bromide (N+C5His2C14), or hexadecyltrimethylammonium bromide (CTAB). The reaction afforded the corresponding pyridoxal analogue (C12SPL) and alanine as the final products upon addition of edta which liberates the copper(II) ion from the coordination sites of the aldimine Schiff-base. The coordination interaction between the copper(II) ion and C12SPM, which takes place prior to the transamination, was clarified by electronic spectroscopy. The reactivity of the 2:1 (ketimine:CuII) complex was found to be much larger than that of the 1:1 complex in the molecular assemblies of N+C5Ala2C14 and CTAB, and the formation of the former species was more pronounced in the N+C5Ala2C14 vesicle. The bilayer vesicle formed with N+C5His2C14 allowed the formation of the 1:1 complex in preference to that of the 2:1 complex, and the coordination-free imidazolyl group of the amphiphile effectively catalyzed the isomerization as a general base.

Artificial Enzymes

“…Catalytic behavior of the functionalized bilayer membrane was first examined in detail with regard to the half-transamination reaction, the transformation of pyruvic acid to alanine. The molecular assembly was constituted in combination of a peptide lipid having an l -alanine ( 31 ) or an l -histidine residue ( 32 ), a pyridoxamine derivative bearing a single chain ( 35b ) or a double chain ( 36b ), and Cu(II) ions in aqueous media at pH 7 and 30.0 °C. − The reaction proceeded through fast equilibrated formation of the Cu(II) complex of a ketimine Schiff base derived from pyruvic acid and the pyridoxamine derivative, followed by slower conversion into the corresponding aldimine Cu(II) chelate. The observed rate constant for the isomerization process showed significant dependence on the Cu(II) ion concentration, reflecting formation of the 2:1 and 1:1 [ketimine−Cu(II)] chelate species.…”

Emergent properties arising from the assembly of amphiphiles. Artificial vesicle membranes as reaction promoters and regulators

“…[132][133][134][135][136][137][138][139][140][141][142] However, since it is somewhat more difficult to work with vesicle systems as compared to micelles (as outlined above), 143 the effect of vesicles as reaction ''promoters'' and ''regulators'' is much less explored. Important early contributions were from the groups of Kunitake, 144,145 Murakami, [146][147][148] Moss, 147,149 Groves, 150,151 and Nolte, 152 as comprehensively and competently discussed previously by Scrimin. 134 With a few selected examples some of the early work in this field will be mentioned, together with highlights of the more recent developments.…”

“…6), the complexation of inorganic ions as catalysts (or co-catalysts) in vesicle membranes is also possible, as for example demonstrated by Murakami and coworkers. 133,135,146,148,171 In this pioneering and very detailed work, the transamination of the hydrophobic amino acid L-Phe with pyruvate, a hydrophilic a-keto acid, was investigated and found to be catalyzed at pH = 5.1 (T = 30 1C) by vesicle membranes composed of a mixture of two cationic amphiphiles, one bearing a pyridoxamine group (abbreviated as PL + 2C 16 ), the other bearing a histidyl residue (N + C 5 His2C 16 ), and copper(II) ions as the inorganic ions. The reaction products obtained from L-Phe and pyruvate are Ala (as racemate) and phenylpyruvate, see Fig.…”

“…Fig.7Schematic representations of a vesicular aminotransferase-mimicking system, as developed by Murakami and collaborators 133,135,146,148,171. (A) A mixture of the hydrophobic amino acid L-phenylalanine and the hydrophilic pyruvate is converted at pH = 5.1 into alanine and phenylpyruvate in the presence of vesicles formed from PL + 2C 16 (a hydrophobic pyridoxamine derivative) and N + C 5 His2C 16 in the presence of copper(II) ions.…”

Transamination reaction of hydrophobic pyridoxal with an α-amino acid in functionalized bilayer vesicles: co-operative catalysis by the imidazolyl group and copper(II) ions

“…We have based our work on the following information: (i) that Schiff-base formation between pyridoxal and a hydrophobic a-amino acid is much enhanced in molecular aggregates such as micelles and vesicles, so that the overall transamination reaction is considerably accelerated;'-3 (ii) a positive charge on the pyridyl nitrogen of pyridoxal provides an electron sink which promotes the a-hydrogen abstraction from an aldimine Schiff-base;2.4 (iii) when the pyridoxal moiety is fixed in the so-called hydrogen-belt domain formed by the histidyl residues interposed between the hydrophobic and hydrophilic zones within the vesicles, the imidazolyl group induces an intramolecular prototropic shift to give the corresponding ketimine Schiff-base and accelerates the overall transamination reaction.1. 3 We report here on the transamination reaction of PL+2C16t with L-phenylalanine (L-Phe) (Scheme 1) in single-walled bilayer vesicles formed from the synthetic peptide lipids, N+ CSAla2CI66 and N + C5His2C Aqueous dispersions of either of the peptide lipids (1.0 x 10-3 mol dm-3) containing PL+2CI6 (5.0 x 10-5 mol dm-3) in an aqueous carbonate buffer (2.0 X 10-2 mol dm-3, pH 9.9, p 0 . 1 0 ~ with KCl) were sonicated for 1 min with a probe-type sonicator at 30 W to give single-walled bilayer vesicles.…”