Rational Design of a Fluorescent Chromophore as a Calcium Receptor via DFT and Multivariate Approaches

Computational and experimental approaches were adopted to utilize a chromophore diglycolic functionalized fluorescein derivative as a Ca(2+) receptor. Fluorescein diglycolic acid (Fl-DGA, 1) was synthesized and used in multivariate determination of Ca(2+) and K(+). Full-structure computation shows that the complexes of 1 and Ca(2+) have comparable energies regardless of additional interaction with lactone moiety. The initial formation of diglycolic-Ca(2+) complex followed by macrocyclization is thermodynamically disfavored. A U-shaped pre-organized 1 allows Ca(2+) to interact simultaneously with diglycolic and lactone motifs. Both motifs actively participate in Ca(2+) recognition and the eleven methylene units in the undecyl arm provides excellent flexibility for reorganization and optimum interaction. Principal component analysis (PCA) of computational molecular properties reveals a simple method in evaluating motifs for cation recognition. Fragment models support full-structure results that negative charge causes significant structural changes, but do not reproduce the full extent of C-O bond breaking observed in the latter. Experimental optical responses show that 1 is selective towards Ca(2+) and discriminates against K(+) and Mg(2+). PCA of emission intensities affords distinct clusters of 0.01, 0.1 and 1 mM Ca(2+) and K(+), and suggests applicability of this technique for simultaneous determination of cationic plant macronutrients in precision agriculture and a wide variety of other applications.