Azido-derivatized compounds as IR probes of local electrostatic environment: Theoretical studies

A variety of spectroscopic probe molecules have been used to study the local electrostatic environment in proteins. Particularly, a few IR probes such as nitrile- and thiocyanate-derivatized amino acids were found to be quite useful not just because they are small but also because their IR absorption frequencies strongly depend on the strengths of hydrogen bonds with the surrounding protic solvent molecules. Recently, we experimentally demonstrated that azido-derivatized alanine is an excellent IR probe for studying structural change in protein in solution. The asymmetric stretching mode frequency of CN₃ -group becomes blueshifted when it is dissolved in water. Such a blueshifting behavior upon hydrogen-bonding interaction with protic solvent molecules was commonly found in other IR probes containing a triple bond such as CN and SCN groups. In this paper, theoretical descriptions on the solvatochromic frequency shift and fluctuation of the azido stretch frequency are presented by carrying out ab initio calculations and both classical and quantum mechanical/molecular mechanical dynamics simulation studies for azidomethane and azidoalanine dipeptide dissolved in water. Two different methods developed here are based on the distributed multipole interaction models, and they are shown to be useful to describe site-specific hydrogen-bonding interaction-induced red- or blueshift of the azido stretch frequency. To test the validity of thus obtained interpolation formula, numerically simulated IR spectra of azidomethane and azidoalanine dipeptide in water are directly compared with experimental results. We anticipate that the present theoretical approaches will be of use in connecting experimentally measured azido stretch frequency to conformational change in protein containing this azido-derivatized alanine residue.