Electrophilicity Descriptors in Urea- and Thiourea-Based Receptors

Abstract

A computational analysis employing representative electrophilicity descriptors, mainly derived from Conceptual DFT, together with molecular electrostatic potential (MEP) calculations, is presented for a set of urea- and thiourea-based receptors relevant to anion recognition. This approach focuses on establishing correlations between electrophilicity and anion affinity, an important property in the design of chemosensors. The relationship between electrophilicity and anion affinity was examined for diaryl urea and thiourea derivatives bearing electron-withdrawing substituents using global descriptors derived from parabolic models of E(N), including the electrophilicity index (ω), electroaccepting power (ω⁺), net electrophilicity (Δω^±), and electrophilic channel (ΔN_A^ele), as well as Hirshfeld atomic charges within the information-theoretic approach (ITA). Experimental association constants for arylthiourea receptors showed acceptable correlations with the computed descriptors. The results highlight that the electrophilic character of the urea and thiourea subunits, together with the electron-deficient anion-binding region (NH) identified through MEP calculations and Hirshfeld atomic charges, are key factors governing anion affinity. Interestingly, the highest Hirshfeld atomic charge among the hydrogen atoms in the NH region ($q_H$) plays an important role in anion affinity, consistent with the deprotonation of several urea and thiourea subunits upon association with anions.

This simple computational methodology enables the ranking of receptors with common molecular architecture according to their electrophilicity and, consequently, their anion affinity, provided that free access to the NH binding region is maintained and conformational flexibility is limited.