NMR Spin–Spin Coupling Constants in Polymethine Dyes as Polarity Indicators

Herein, we explore the use of spin–spin coupling constants (SSCCs) in merocyanine (MCYNE) dyes as indicators of polarity. For this purpose, we use Car–Parrinello hybrid quantum mechanics/molecular mechanics (QM/MM) to determine the structures of MCYNE in solvents of different polarity, followed by computations of the SSCCs by using QM/MM linear‐response theory. The molecular geometry of MCYNE switches between neutral, cyanine‐like, and zwitterionic depending on the polarity of the solvent. This structural variation is clearly reflected in the proton SSCCs in the polymethine backbone, which are highly sensitive to the dielectric nature of the environment; this mechanism can be used as a “polarity indicator” for different microenvironments. This result is highlighted by computing the SSCCs of the MCYNE probe in the cavity of the beta‐lactoglobulin protein. The computed SSCCs clearly indicate a non‐polar hydrophobic dielectric nature of this cavity.