Side Methyl Groups Control the Conformation and Contribute to Symmetry Breaking of Isoprenoid Chromophores

Ab initio DFT computations reveal that the essential structural and photophysical features of the conjugated π-electron system of retinal and carotenoids are dictated by "innocent" methyl substituents. These methyl groups shape the conformation and symmetry of the isoprenoid chromophores by causing a sigmoidal distortion of the polyene skeleton and increasing its flexibility, which facilitates fitting to their binding pockets in proteins. Comparison of in vacuo conformations of the chromophores with their native (protein-bound) conformations showed, surprisingly, that the peripheral groups and interactions with the protein environment are much less significant than the methyl side groups in tuning their structural features. The methyl side groups also contribute to a loss of symmetry elements specific to linear polyenes. In effect, the symmetry-imposed restrictions on the chromophore electronic properties are disabled, which is of tremendous relevance to their photophysics. This is evidenced by their non-negligible permanent dipole moments and by the simulated and experimentally measured circular dichroism spectra, which necessarily reflect the chirality of the conjugated π-electron system.