The interactions of caffeine and theophylline with divalent cadmium, mercury, strontium and barium ions were studied in aqueous solution and physiological pH. Fourier transform infrared spectroscopy (FTIR) and absorption spectra were used to determine the cation binding mode and association constants. Spectroscopic results showed that Cd²⁺, Hg²⁺, Sr²⁺ and Ba²⁺ bind strongly to caffeine and theophylline. Direct and indirect (through metal hydration shell) interactions were observed for caffeine and theophylline with Cd²⁺, Hg²⁺, Sr²⁺ and Ba²⁺ through O6 and N9 (caffeine) and O6, N9 and N7 atoms (theophylline). The overall binding constants are:

k(Cd-caffeine) = 1.24 × 10⁵ M^-1, k(Hg-caffeine) = 1.74 × 10⁵ M^-1, k(Sr- caffeine) = 3.3 × 10⁴ M^-1, k(Ba-caffeine) = 1.8 × 10⁴ M^-1, k(Cd-theophylline) = 5.75 × 10⁵ M^-1, k(Hg-theophylline) = 2.14 × 10⁵ M^-1, k(Sr-theophylline) = 4.6 × 10⁴ M^-1, k(Ba-theophylline) = 3 × 10⁴ M^-1.

These k values are evidence for weak and strong cation interactions in these metal complexes.