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

Abstract

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 Δ H ° = −74 ± 4 kJ mol –1 is deduced for the formation of H-bonded p -cresol/dodecylguanidine in hexane. Δ E = −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.

Anhydrous Monoalkylguanidines in Aprotic and Nonpolar Solvents: Models for Deprotonated Arginine Side Chains in Membrane Environments

“…In fact, IR spectra (Figure 1D,E) and the 15 N NMR CPMAS spectrum (Figure 4B) of the crystalline product ( 15 , 15′ ) show that the free base of this compound exists predominantly in a zwitterionic form in this crystal. X-ray structures in the accompanying paper 23 demonstrate that these zwitterions form head-to-tail H-bonded dimers in crystals. Concentration-dependent spectroscopy supports formation of similar dimers in DMSO solution above ∼30 mM.…”

“…However, the accompanying paper 23 also shows that different results are observable for 1:1 mixtures of dodecylguanidine ( 2 ) and p -cresol in even less-polar solvents, for example, hexane. In such water-free environments, strong intermolecular H-bonds are formed that correspond more closely to a neutral H-bonded pair (phenol + guanidine).…”

“…Our hypothesis that a different nonzwitterionic structure for 15 may prevail in membrane-like solvent environments is explored in the accompanying paper. 23 There, it is determined spectroscopically that very strong stoichiometric H-bonding of 15 occurs in aprotic solvents. Specifically, head-to-tail H-bonded homodimer complexes of 15 readily form in DMSO, with partial proton transfer from guanidine back to phenol.…”

“…Similar H-bonded heterodimer complexes of dodecylguanidine ( 2 ) with p -cresol are even soluble to ∼1 mM in hexane. 23 The latter complexes exist nearly 50:50 as two main protomers in rapid equilibrium: not only dodecylguanidinium/cresolate, but also fully neutral cresol/dodecylguanidine.…”

Investigation of proteinaceous paint layers, composed of egg yolk and lead white, exposed to fire-related effects

“…In the E-3a spectrum the signals at 1607 (ν(CC)ring, δ(CH)), 1455 (δ(CH 2 )), 1272 (ν(CO), ν(CC)), 1237 cm ‒ 1 (δ(COH)) are the characteristic bands of tyrosine amino acid 27 . Moreover, in this transmission spectrum some additional peaks could belong to different aromatic compounds (e.g., p-cresol, phenol, and 4-methylphenol) and are at 1610, 1272, 1205, 1173, 1123 and 1052 cm ‒1 28 , 29 . Most likely, the signals in the lower-medium IR region apparently belong to vibrations of the arene ring, substituted with different molecular groups.…”