Modulations in the binding selectivity of phenol and thiophenol with ethyl cinnamate: an IR spectroscopic and quantum chemical investigation

Complexes of (E)-ethylcinnamate (EC), a widely prevalent plant secondary metabolite, with two hydrogen bond donors phenol (Ph) and thiophenol (TPh), have been studied under ambient conditions in solution. The former, characterized by multiple electron-rich centers, offers multiple accessible sites to which the phenolic O-H donor or the thiophenolic S-H donor can bind. Experimental shifts in donor stretching frequencies as well as in signature vibrations of the acceptor EC molecule are interpreted in combination with quantum chemical calculations to assign the binding preferences of both Ph and TPh. It is observed that the phenolic O-H binds almost exclusively to the highly electronegative carbonyl oxygen on EC through an O-H⋯O H-bond. However, there is a loss of selectivity in the case of the thiophenolic S-H donor, which shows equal propensity to bind both to the oxygen centres through the S-H⋯O H-bond and to the more diffuse benzene π-cloud on EC, through the S-H⋯π H-bond. The observations suggest that the S-H⋯π H-bond is strong enough to compete with the S-H⋯O H-bond, unlike the O-H⋯π H-bond, which is always a weaker variant of the conventional O-H⋯O type. Noticeable changes are observed in predicted geometries at the H-bond interfaces for the thiophenolic complexes, as compared to the phenolic complexes. While dispersion plays a major role in the stabilization of both EC-Ph and EC-TPh complexes, the observed modulations in intermolecular binding are largely an outcome of the delicate interplay of electrostatic and dispersion interactions. Specific binding preferences appear to be the effect of inherent attributes of donor-acceptor groups. TPh, being an acid of "softer" nature, has a greater tendency to bind to the "softer" π-electron acceptor site on EC, compared to the "harder" phenolic donor Ph, which prefers the "harder" and more electronegative carbonyl oxygen site. The results lend additional insights into the subtle effects of heavier atom substitution on biomolecular recognition.