Supramolecular Photochirogenesis with Biomolecules. Mechanistic Studies on the Enantiodifferentiation for the Photocyclodimerization of 2-Anthracenecarboxylate Mediated by Bovine Serum Albumin

• Published in: Journal of organic chemistry Vol. 72; no. 8; pp. 2707 - 2715
• Main Authors: Nishijima, Masaki, Pace, Tamara C. S, Nakamura, Asao, Mori, Tadashi, Wada, Takehiko, Bohne, Cornelia, Inoue, Yoshihisa
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 13.04.2007
• Subjects: Animals; Anthracenes - chemistry; Anthracenes - metabolism; Binding Sites; Carboxylic Acids - chemistry; Carboxylic Acids - metabolism; Cattle; Chemistry; Circular Dichroism; Condensed benzenic and aromatic compounds; Cyclization; Dimerization; Exact sciences and technology; Fluorescence; General and physical chemistry; Kinetics and mechanisms; Organic chemistry; Photochemistry; Physical chemistry of induced reactions (with radiations, particles and ultrasonics); Preparations and properties; Protein Binding; Reactivity and mechanisms; Serum Albumin, Bovine - pharmacology; Spectrometry, Fluorescence; Stereoisomerism; Water; Exciton; Fluorescence; Molecular interaction; Chiral compound; Selectivity; Hydrophobicity; Photochemical reaction; Fluorescence spectrometry; Nitromethane; Carboxylic acid; Supramolecular structure; Reaction mechanism; Aromatic compound; Rate constant; Protection; Ungulata; Photochemistry; Bovine; Hydrophobic compound; Serum albumin; Anthracene derivatives; Steady state; Circular dichroism; Time resolution; Vertebrata; Mammalia; Affinity; Enantiomeric excess; Artiodactyla; Spectrophotometry
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo062226b

Photophysics and photochemistry of 2-anthracenecarboxylate (AC) bound to bovine serum albumin (BSA) were investigated in detail for the first time by electronic absorption, circular dichroism (CD), steady-state and time-resolved fluorescence, fluorescence quenching, and product analysis studies. Through the spectroscopic investigations, it was revealed that the four independent binding pockets of BSA, which are known to accommodate 1, 3, 2, and 3 AC molecules in the order of decreasing affinity, are distinctly different in hydrophobicity, chiral environment, and accessibility. Interestingly, AC bound to site 1 gave highly structured fluorescence with dual lifetimes of 4.8 and 2.1 ns in an intensity ratio of 3:2, which may be assigned to the existence of two positional or orientational isomers within the very hydrophobic site 1. In contrast, the lifetime of AC in site 2 was much longer (13.3 ns), and ACs in sites 3 and 4 have broader fluorescence spectra with lifetimes that were practically indistinguishable from that in bulk water (15.8 ns). Although each of sites 2−4 simultaneously binds multiple AC molecules, no CD exciton coupling or static fluorescence quenching was detected, indicating that ACs bound to each site are not in close proximity to each other. Quenching studies with nitromethane further confirmed the significant difference in accessibility among the binding sites; thus, ACs bound to sites 1 and 2 are highly protected from the attack of the quencher, affording 32 and 10 times smaller rate constants than that for free AC in water. Product studies in the presence and absence of nitromethane more clearly revealed the photochirogenic performance of each binding site. Although the addition of nitromethane did not greatly alter the product distribution, the enantiomeric excesses (ee's) of chiral cycloadducts 2 and 3 were critically manipulated by selectively retarding the photoreaction occurring at the more accessible binding sites. Thus, the highest ee of 38% was obtained for 2 in the presence of 18 mM nitromethane, while the highest ee of 58% was attained for 3 in the absence of nitromethane, both at [AC]/[BSA] = 3.6.