Nitric oxide (NO^•) has long attracted interest in chemistry and biochemistry. In fact the establishment of NO^• as the endothelium-derived relaxing factor (EDRF) won the Nobel Prize in Chemistry and Physics in 1998^1-3 and established its vital role in cardiovascular signaling. It has since been used as a first line of defense in the treatment of heart failure. However, the overuse of exogenous NO^• leads to pathological effects due to its radical nature.⁴ These limitations have driven research into the redox congeners of NO^• (i.e. NO⁺ and NO^-); particularly the reduced analog, NO^- (nitroxyl). Because of the relatively high pK_a of NO^- (11.6⁵) it exists primarily in the protonated form, HNO, under physiological conditions. HNO has shown diverse pharmacological potential including alcohol aversion therapy⁶, anticancer activity⁷ and cardiovascular protection (using Cimlanod, currently in Phase 2a clinical trials⁸). While the potential for HNO is vast, studying this molecule has proven difficult due to its instability (2 HNO → N₂O + H₂O, k = 10⁶ M^-1 s^-1)⁹ necessitating the need for donors with biological compatibility. Proposed Fe bound HNO complexes as intermediates in the Global Nitrogen Cycle (GNC) suggest the use of a metal center to stabilize HNO.¹⁰ In this work a series of {CoNO}⁸ (Enemark-Feltham notation; {MNO}ⁿ, where n = M d + NO Π^* electrons)¹¹ was synthesized with systematic modifications to the ligand frame to tune the HNO releasing behavior. The HNO donor properties of these complexes were evaluated using standard detection methods.^{12, 13} In addition, reduction to {CoNO}⁹ was also explored to enhance reactivity, as the Co^III metal center in {CoNO}⁸ is expected to favor stability over HNO release. 

(1) Murad, F. Angewandte Chemie International Edition 1999, 38, 1856-1868.

(2) Furchgott, R. F. Angewandte Chemie International Edition 1999, 38, 1870-1880.

(3) Ignarro, L. J. Angewandte Chemie International Edition 1999, 38, 1882-1892.

(4) Snyder, S. H. Nature 1993, 364, 577-577.

(5) Bartberger, M. D.; Liu, W.; Ford, E.; Miranda, K. M.; Switzer, C.; Fukuto, J. M.; Farmer, P. J.; Wink, D. A.; Houk, K. N. Proceedings of the National Academy of Sciences 2002, 99, 10958-10963.

(6) DeMaster, E. G.; Redfern, B.; Nagasawa, H. T. Biochem Pharmacol 1998, 55, 2007-2015.

(7) Augustyniak, A.; Skolimowski, J.; Błaszczyk, A. Chemico-Biological Interactions 2013, 206, 262-271.

(8) Tita, C.; Gilbert, E. M.; Van Bakel, A. B.; Grzybowski, J.; Haas, G. J.; Jarrah, M.; Dunlap, S. H.; Gottlieb, S. S.; Klapholz, M.; Patel, P. C.; et al. European Journal of Heart Failure 2017, 19, 1321-1332.

(9) Miranda, K. M. Coordination Chemistry Reviews 2005, 249, 433-455.

(10) Speelman, A. L.; Lehnert, N. Accounts of Chemical Research 2014, 47, 1106-1116.

(11) Enemark, J. H.; Feltham, R. D. Coordination Chemistry Reviews 1974, 13, 339-406.

(12) Bari, S. E.; Martí, M. A.; Amorebieta, V. T.; Estrin, D. A.; Doctorovich, F. Journal of the American Chemical Society 2003, 125, 15272-15273.

(13) Reisz, J. A.; Klorig, E. B.; Wright, M. W.; King, S. B. Organic Letters 2009, 11, 2719-2721.