The Hydrophobic and Metal‐Ion Coordinating Properties of α‐Lipoic Acid—An Example of Intramolecular Equilibria in Metal‐Ion Complexes

Abstract

Hydrophobic interactions as structure determining factors for macromolecules are wellknown in biochemistry. Considerably less recognized is the fact that these low-energy interactions may also determine the structure of low-molecular species. The same applies for weak ligand-metal ion interactions. That both these factors may lead to intramolecular, concentration-independent equilibria between isomeric metal-ion complexes is demonstrated with a-lipoic acid as ligand. This cofactor offers metal ions two different binding sites: the carboxylate group and the disulfide linkage. The carboxylate group dominates the coordinating properties of this ligand towards the biologically important metal ions, but a disulfide-metal ion interaction is still possible and under sterically favorable conditions may become very important; this could also be true under enzymic conditions where the carboxyl group is no longer free but amide-linked to the protein. Furthermore, due to the valeric acid side chain, the lipoyl moiety is ideally suited to undergo hydrophobic ligand-ligand interactions in mixed-ligand complexes. Such hydrophobic interactions seem to be ideal to allow migration, e . g . , of the 14 A long lipoyllysyl moiety, and also to facilitate the correct 'fixation' at the surface of the enzyme.

Complexation of Hg2+ with α‐Lipoic and Dihydrolipoic Acids: Study by Differential Pulse Voltammetry on Rotating Au‐Disk Electrode and ESI‐MS

“…However, for higher DHLA/Hg 2þ ratios (2 : 1 and 4 : 1) the stable species detected by ESI-MS involve more than one DHLA molecule: Hg 2 (DHLA) 2 Hg(DHLA) 2 , Hg 2 (DHLA) 4 and Hg 4 (DHLA) 4 .…”

“…Several peaks attributed to Hg 2þ -DHLA complexes are detected at higher ligand concentrations (L/M of 2 : 1 and 4 : 1). Signals were detected at m/z ¼ 813.03, 615.07, 1219.03 and 1628.04, which were assigned to Hg 2 (DHLA) 2 Hg(DHLA) 2 , Hg 2 (DHLA) 4 and Hg 4 (DHLA) 4 complexes, respectively. The formation of polynuclear species could be explained in a similar way to that reported for the complexes of Hg 2þ with chelation therapy agents DMSA and DMPS [24]: due to the short distance between two thiol groups in the chelator, only the participation of several chelatant moieties could provide the stable linear conformation with two thiol groups for each Hg 2þ .…”

“…In ALA the disulfide bond can participate in metal chelation, although the stability of this binding should be very weak for the majority of metal ions [4]. However, soft metals like Cu þ , Ag þ or Hg 2þ tend to bind the disulfide bond causing its cleavage [4].…”

“…However, soft metals like Cu þ , Ag þ or Hg 2þ tend to bind the disulfide bond causing its cleavage [4].…”

Applications of liver acetone powders in enantioselective synthesis

“…57 We have successfully synthesized (S)-oct-1-en-3-ol, a well known pheromone matsutake alcohol, 58 a flavor component of the mushroom Tricholoma matsutake, in 92% enantiomeric purity via the enzymatic hydrolysis of racemic 3-acetoxyoct-1-ene using bovine liver acetone powder (BLAP) according to Scheme 9. 59 Racemic 8-(tetrahydro-pyran-2-yloxy)-3-acetoxyoct-1-ene was enantioselectively hydrolyzed with BLAP to provide (3S)-8-(tetrahydropyran-2-yloxy)oct-1-en-3-ol, in 93% enantiomeric purity which was subsequently transformed into (3S)-1,3,8-octanetriol, an important synthon, for synthesis of lipoic acid, a co-enzyme associated with α-keto acid dehydrogenases, 60,61 following the reaction sequence as described in the Scheme 10. Synthesis of enantiomerically enriched cyclic ketones continues to attract the attention of organic chemists because of the utility of these molecules as chiral building blocks in the synthesis of natural products.…”