Experimental and Computational Modeling of H‑Bonded Arginine–Tyrosine Groupings in Aprotic Environments

H-bonds between neutral
tyrosine and arginine in nonpolar environments
are modeled by small-molecule phenol/guanidine complexes. From the
temperature and concentration dependence of UV spectra, a value of
ΔH° = −74 ± 4 kJ mol–1 is deduced for the formation of H-bonded p-cresol/dodecylguanidine
in hexane. ΔE = −71 kJ mol–1 is computed with density functional theory (in vacuo). In dimethyl
sulfoxide or crystals, (p-phenolyl)­alkylguanidines
form head-to-tail homodimers with two strong H-bonding interactions,
as evidenced by UV, IR, and NMR spectral shifts, strong IR continuum
absorbance bands, and short O···N distances in X-ray
crystal structures. Phenol/alkylguanidine H-bonded complexes consist
of polarizable rapidly interconverting tautomers, with the proton
shift from phenol to guanidine increasing with increase in the polarity
of the aprotic solvent. As measured by NMR, both groups in these strongly
H-bonded neutral complexes can simultaneously appear to be predominantly
protonated. These systems serve as models for the hypothetical hydrogen-Bonded
Uncharged (aRginine + tYrosine), or “BU­(RY)”, motifs
in membrane proteins.