EaStCHEM School of Chemistry, University of Edinburgh , Joseph Black Building, David Brewster Road, Edinburgh EH9 3FJ, U.K.
Syngenta, Jealott's Hill International Research Centre, Bracknell, Berkshire RG42 6EY, U.K.
J Am Chem Soc. 2017 Oct 25;139(42):15160-15167. doi: 10.1021/jacs.7b08511. Epub 2017 Oct 17.
Favorable molecular interactions between group 16 elements have been implicated in catalysis, biological processes, and materials and medicinal chemistry. Such interactions have since become known as chalcogen bonds by analogy to hydrogen and halogen bonds. Although the prevalence and applications of chalcogen-bonding interactions continues to develop, debate still surrounds the energetic significance and physicochemical origins of this class of σ-hole interaction. Here, synthetic molecular balances were used to perform a quantitative experimental investigation of chalcogen-bonding interactions. Over 160 experimental conformational free energies were measured in 13 different solvents to examine the energetics of O···S, O···Se, S···S, O···HC, and S···HC contacts and the associated substituent and solvent effects. The strongest chalcogen-bonding interactions were found to be at least as strong as conventional H-bonds, but unlike H-bonds, surprisingly independent of the solvent. The independence of the conformational free energies on solvent polarity, polarizability, and H-bonding characteristics showed that electrostatic, solvophobic, and van der Waals dispersion forces did not account for the observed experimental trends. Instead, a quantitative relationship between the experimental conformational free energies and computed molecular orbital energies was consistent with the chalcogen-bonding interactions being dominated by n → σ* orbital delocalization between a lone pair (n) of a (thio)amide donor and the antibonding σ* orbital of an acceptor thiophene or selenophene. Interestingly, stabilization was manifested through the same acceptor molecular orbital irrespective of whether a direct chalcogen···chalcogen or chalcogen···H-C contact was made. Our results underline the importance of often-overlooked orbital delocalization effects in conformational control and molecular recognition phenomena.
第 16 族元素之间有利的分子相互作用在催化、生物过程以及材料和药物化学中都有涉及。这种相互作用类似于氢键和卤键，后来被称为硫属键。虽然硫属键相互作用的普遍性和应用仍在不断发展，但对于这类 σ-空穴相互作用的能量意义和物理化学起源仍存在争议。在这里，我们使用合成分子天平对硫属键相互作用进行了定量实验研究。在 13 种不同的溶剂中测量了超过 160 个实验构象自由能，以研究 O···S、O···Se、S···S、O···HC 和 S···HC 接触的能量以及相关的取代基和溶剂效应。结果发现，最强的硫属键相互作用至少与常规氢键一样强，但与氢键不同的是，它们出人意料地与溶剂无关。构象自由能与溶剂极性、极化率和氢键特征无关，这表明静电、疏溶剂和范德华色散力不能解释观察到的实验趋势。相反，实验构象自由能与计算分子轨道能量之间的定量关系表明，硫属键相互作用主要由孤对（n）的 n → σ轨道离域和供体硫代（硒代）酰胺与受体噻吩或硒吩的反键 σ轨道之间的相互作用决定。有趣的是，无论是否形成直接的硫属···硫属或硫属···H-C 接触，稳定性都是通过相同的受体分子轨道来体现的。我们的研究结果强调了在构象控制和分子识别现象中常常被忽视的轨道离域效应的重要性。
