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.

非极性环境中中性酪氨酸与精氨酸之间的氢键（hydrogen bond），可通过小分子苯酚/胍复合物进行建模。基于紫外光谱（ultraviolet spectroscopy, UV）的温度与浓度依赖特性，可推导出正己烷中氢键结合型对甲酚/十二烷基胍形成过程的标准焓变ΔH° = −74 ± 4 kJ mol–1。通过密度泛函理论（density functional theory）（真空环境下）计算得到的能量变化ΔE为−71 kJ mol–1。在二甲基亚砜（dimethyl sulfoxide, DMSO）或晶体状态下，(对羟苯基)烷基胍可形成头尾相接的同型二聚体，该结构存在两处强氢键相互作用；这一结论可通过紫外、红外光谱（infrared spectroscopy, IR）、核磁共振波谱（nuclear magnetic resonance, NMR）的谱峰位移，强红外连续吸收带，以及X射线晶体结构（X-ray crystal structure）中较短的O···N距离得以验证。苯酚/烷基胍氢键复合物由可极化且快速互变的互变异构体组成，随着非质子溶剂极性增强，质子从苯酚转移至胍的程度会随之升高。经核磁共振波谱测定，这类强氢键结合的中性复合物中的两个官能团，可同时呈现出主要处于质子化状态的特征。此类系统可作为膜蛋白中假想的氢键结合中性（精氨酸+酪氨酸）基序——即"BU(RY)"——的研究模型。