Sialidase Inhibitors with Different Mechanisms.

Sialidases, or neuraminidases, are enzymes that catalyze the hydrolysis of sialic acid (Sia)-containing molecules, mostly removal of the terminal Sia (desialylation). By desialylation, sialidase can modulate the functionality of the target compound and is thus often involved in biological pathways. Inhibition of sialidases with inhibitors is an important approach for understanding sialidase function and the underlying mechanisms and could serve as a therapeutic approach as well. Transition-state analogues, such as anti-influenza drugs oseltamivir and zanamivir, are major sialidase inhibitors. In addition, difluoro-sialic acids were developed as mechanism-based sialidase inhibitors. Further, fluorinated quinone methide-based suicide substrates were reported. Sialidase product analogue inhibitors were also explored. Finally, natural products have shown competitive inhibiton against viral, bacterial, and human sialidases. This Perspective describes sialidase inhibitors with different mechanisms and their activities and future potential, which include transition-state analogue inhibitors, mechanism-based inhibitors, suicide substrate inhibitors, product analogue inhibitors, and natural product inhibitors.

Structures and Energetics of NI3 and N2 I4.

We have applied new methods for performing coupled-cluster calculations to small molecules containing iodine atoms; specifically, NI3 and N2 I4 . Because NI3 is known to be very reactive, attempts to measure its thermodynamic properties have been challenging at best. To date, N2 I4 has not been isolated, and our results suggest that its isolation will be just as challenging. We find that the ΔHf (NI3 )=+307.7 kJ mol-1 and ΔHf (N2 I4 )=+551.6 kJ mol-1 , confirming that they are unstable with respect to their decomposition products N2 and I2 .