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.