Synthesis of N-heteroaryl retinals and their artificial bacteriorhodopsins.

N-Heteroaryl retinals derived from indole, 1-indolizine and 3-indolizine (10 a-c) have been synthesized after their UV/Vis red-shifted absorption properties had been predicted by time-dependent density functional theory (TD-DFT) computations. The three new analogues form artificial pigments upon recombination with bacterioopsin: indolyl retinal 10 a undergoes fast and efficient reconstitution to form a species with a UV/Vis absorbance maximum similar to that of wild-type bacteriorhodopsin, whilst the indolizinyl retinals 10 b and 10 c also reconstitute in significant proportion to give noticeably red-shifted, although unstable, pigments. Significant changes in the pK(a) values of these artificial bacteriorhodopsins are interpreted as arising from nonoptimal binding-site occupancy by the chromophore due to steric constraints.