Chemical Control of Aggregation-Induced Enhancement via β-Galactose and Gadolinium Chelates

Tetraphenyl ethylene (TPE)–gadolinium (Gd3+) probes were synthesized to evaluate the effects of chelate structure and β-galactose functionalization on aggregation-induced enhancement (AIE). Five derivatives were prepared featuring azamacrocyclic Gd3+ chelates bearing three acetates and a fourth coordinating group such as an acetate (TPE-1a/b), alcohol (TPE-2a/b), or amide (TPE-3a), with either an alkyl or triazole linker. The opposite side of the TPE core contained either an alcohol (a) or β-galactose (b). Relaxivity (r1) and fluorescence measurements revealed that β-galactose substitution increased aqueous solubility and raised the critical aggregation concentration (CAC), as observed for TPE-1a (19.7 μM) versus TPE-1b (102.6 μM). Dynamic light scattering (DLS) showed that TPE-1a forms aggregates of uniform size above the CAC, consistent with a linear increase in relaxivity due to greater aggregate concentration rather than growth in particle size. Negatively charged TPE-1a/b derivatives were more soluble than neutral TPE-2a/b analogues; TPE-2a was insoluble and TPE-2b remained aggregated. TPE-1a exhibited the largest r1 increase upon AIE (4.2 to 24.1 mM–1 s–1 at 1.41 T, 37 °C), whereas TPE-3a showed the greatest fluorescence enhancement (ΦF = 4.0%). Functionalization at the glycosidic position with TPE inhibited β-galactosidase activity.