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

Abstract

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.

Novel Strategy of Supramolecular Asymmetric Photochirogenesis with Tailor-Made Biopolymers as Chiral Reaction Fields

“…The striking difference observed upon CD spectral titration with HSA and BSA might rationalize the significantly different photochirogenic behavior described below. [4]), was slightly enhanced from 3.7 to 4.9, which was contrast tendency of BSA presence system (HT/HH=0.23). The ee's of 2 and 3 were also enhanced up to 79% and 88% ee, respectively, at HSA/AC ratio of 3.0.…”

“…In this paper, we concentrated on the biopolymer based supramolecular asymmetric photochirogenesis (SMAP) in confined media, which employ proteins, such as human and bovine serum albumins (HSA and BSA) as a chiral photoreaction media [2][3][4].…”

Photoactive assemblies of organic compounds and biomolecules: drug–protein supramolecular systems

“…99 Furthermore, BSA provides a chiral source that has a marked influence on the stereoselectivity of syn-HT and anti-HH dimers formation from achirals ANC, which have been obtained with moderate enantiomeric excess. 99,100 In this context, the photochirogenic properties of the different binding sites have been investigated using nitromethane as quencher of the ANC singlet excited state. 100 The presence of nitromethane results in an increase of the ee of syn-HT, with the concomitant decrease of that of anti-HH.…”

“…It is noteworthy, that the same enantiomer of anti-HH is preferentially formed in both albumins, while the antipodes are favoured in the case of syn-HT. [98][99][100][101]158 To expand the range of biomolecular hosts, the [4+4] photocyclodimerisation of ANC has been investigated in the presence of a molecular chaperone protein, the archaeal prefoldin from Pyrococcus horikoshii OT3 (PFD). 159 In the presence of PFD, Finally, the enantioselective 6 electrocyclisation of a family of photochromic bis-thienylethenes (BTE), namely 1,2-bis(2,5-dimethyl-3-thienyl)hexafluorocyclopentene (BTE-1), 1,2-bis(2-hydroxymethyl-5-methyl-3-thienyl)hexafluorocyclopentene (BTE-2) and 1,2-bis(5-hydroxymethyl-2-methyl-3-thienyl)hexafluorocyclopentene (BTE-3) has also been carried out inside HSA.…”

Proteïnes com a microreactors en fotoquímica supramolecular

“…Els processos descrits fins ara en la bibliografia s"inclouen en l"àrea de la fotoquirogènesi supramolecular. En aquest sentit, els estudis es limiten a alguns treballs relacionats amb la fotodescomposició del binaftol [172] , la fotodeshalogenació del carprofén [173] , la fotociclació de la bilirubina [174] , les fotoisomeritzacions de les colquicines [175] , la fotodescarboxilació del ketoprofén [176,177] , la fotooxidació de l"antracé [178] i la fotodimerització de l"àcid antracé-2-carboxílic en presència d"albúmina sèrica humana i/o bovina [179][180][181] . A grans trets, el que aquests exemples mostren és que la presència de les proteïnes i la inclusió del substrat en un determinat lloc d"unió dins d"aquestes influeix en l"enantio o estereodiferenciació observada per a les reaccions en qüestió i també afavoreix la formació d"uns fotoproductes de manera predominant respecte a uns altres.…”