Minocycline (MIN) and tigecycline (TIG) complexed with Ca2+ substantially more strongly than tetracycline (TC) due to the dimethylamino substituent at C7 that increased electron density at the Ca2+ coordination site.
MIN and TIG preferred higher-order (1Ca2+–3MIN and 2Ca2+–3TIG) complexes at pH 6.8 and 7.5 while TC preferred a 1Ca2+–3TC complex at pH 6.8 but a 1Ca2+–1TC complex at pH 7.5.
TIG formed a different higher order complex than MIN, suggesting the involvement of the N-t-butylglycylamido substituent at C9 in Ca2+ coordination.