Role of Gold in Inflammation and Tristetraprolin Activity

The zinc finger protein tristetraprolin (TTP) regulates inflammation by downregulating cytokine mRNAs. Misregulation results in arthritis, sepsis and cancer, and there is an interest in modulating TTP activity with exogenous agents. Gold has anti-inflammatory properties and has recently been shown to modulate the signaling pathway that produces TTP, suggesting that TTP may be a target of gold. The reactivity of [Au^III(terpy)Cl]Cl₂ with TTP was investigated by UV/Vis spectroscopy, spin-filter inductively coupled plasma mass spectrometry, X-ray absorption spectroscopy and native electrospray ionization mass spectrometry. Au^III was found to replace zinc in the protein active site in the reduced Au^I form, with the Au^I ion coordinated to two cysteine residues in a linear geometry. The replacement of Zn^II with Au^I results in loss of both secondary structure and RNA binding function. In contrast, when Zn^IITTP is bound to its RNA target, no replacement of Zn^II with Au^I is observed, even in the presence of excess Au^IIIterpy. This discovery of differential reactivity of gold with TTP versus TTP/RNA offers a potential strategy for selective targeting with gold complexes to control inflammation.     

Harnessing Brightness in Naphthalene Diimides

The development of brightly emissive compounds is of great research and commercial interest, with established and emerging applications across chemistry, biology, physics, medicine and engineering. Among the many types of molecules available, naphthalene diimides have been widely used for both fundamental photophysical studies and in practical applications that utilise fluorescence as an information readout. The monomeric naphthalene diimide is weakly fluorescent, however through various methods of core-derivatisation, it can be developed to be highly fluorescent and further functionalised to add utility. In this review, we highlight recent advances made in naphthalene diimide chemistry that have led to development of molecules with improved optical properties, and the design strategies utilised to produce bright fluorescence emission as small molecules or in supramolecular architectures.