Two copper-containing compounds [Cu3(μ3-OH)2(H2O)2{(SO3)-C6H3-(COO)2}(CH3COO)], I, and [Cu5(μ3-OH)2(H2O)6{(NO2)-C6H3-(COO)2}4]·5H2O, II, were prepared using sulphoisophthalic and nitroisophthalic acids. The removal of the coordinated water molecules in the compounds was investigated using in situ single crystal to single crystal (SCSC) transformation studies, temperature-dependent powder X-ray diffraction (PXRD), and thermogravimetric analysis (TGA). The efficacy of SCSC transformation studies were established by the observation of dimensionality cross-over from a two-dimensional (I) to a three-dimensional structure, Cu6(μ3-OH)4{(SO3)-C6H3-(COO)2}2(CH3COO)2, Ia, during the removal of the coordinated water molecules. Compound II exhibited a structural reorganization forming Cu5(μ2-OH)2{(NO2)-C6H3-(COO)2}4], IIa, possessing trimeric (Cu3O12) and dimeric (Cu2O8) copper clusters. The PXRD studies indicate that the three-dimensional structure (Ia) is transient and unstable, reverting back to the more stable two-dimensional structure (I) on cooling to room temperature. Compound IIa appears to be more stable at room temperature. The rehydration/dehydration studies using a modified TGA setup suggest complete rehydration of the water molecules, indicating that the water molecules in both compounds are labile. A possible model for the observed changes in the structures has been proposed. Magnetic studies indicate changes in the exchanges between the copper centers in IIa, whereas no such behavior was observed in Ia.