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 (<b>TPE-1a/b</b>), alcohol (<b>TPE-2a/b</b>), or amide (<b>TPE-3a</b>), with either an alkyl or triazole linker. The opposite side of the TPE core contained either an alcohol (<b>a</b>) or β-galactose (<b>b</b>). Relaxivity (<i>r</i>₁) and fluorescence measurements revealed that β-galactose substitution increased aqueous solubility and raised the critical aggregation concentration (CAC), as observed for <b>TPE-1a</b> (19.7 μM) versus <b>TPE-1b</b> (102.6 μM). Dynamic light scattering (DLS) showed that <b>TPE-1a</b> 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 <b>TPE-1a/b</b> derivatives were more soluble than neutral <b>TPE-2a/b</b> analogues; <b>TPE-2a</b> was insoluble and <b>TPE-2b</b> remained aggregated. <b>TPE-1a</b> exhibited the largest r₁ increase upon AIE (4.2 to 24.1 mM^-1 s^-1 at 1.41 T, 37 °C), whereas <b>TPE-3a</b> showed the greatest fluorescence enhancement (Φ_F = 4.0%). Functionalization at the glycosidic position with TPE inhibited β-galactosidase activity.