TiO2-catalyzed synthesis of a primary amine NONOate

Authors

DOI:

https://doi.org/10.15587/2519-4852.2026.342943

Keywords:

HNO donor, TiO2 catalyst, NONOate

Abstract

HNO induces vascular and myocardial activities, exhibits anticancer and antioxidant activities and inhibits platelet aggregation. However, the mechanism by which it functions is still poorly understood. Primary amine NONOates are HNO donors that can be used to study and understand the chemical properties and physiological effects of HNO. However, its synthesis involves very high pressure and low temperature conditions and requires specialized glassware and equipment.

The aim. In this study, a method for the synthesis of an HNO donor, a primary amine NONOate based on cyclohexylamine, that does not involve specialized glassware and high pressure is developed.

Materials and methods. The synthesis of primary amine NONOate was performed through the reaction of cyclohexylamine and NO gas, in the presence of sodium methoxide and TiO2, for 24 h. The resulting product was isolated and characterized spectrophotometrically to determine its identity, decomposition kinetics, and HNO release profile at physiological pH. The synthesis method was further optimized based on reaction time, solvent, catalyst loading, and temperature.

Results. The TiO2-catalyzed method yielded the desired product which was characterized spectrophotometrically. The product shows typical electronic spectrum of a NONOate (λmax = 250 nm), followed first-order decomposition kinetics, and released both HNO and NO at physiological pH, which are characteristics of primary amine NONOate. The method yielded 5.98 mg cyclohexylamine NONOate which is equivalent to a percent yield of 0.0550%. The yield of the method was low but comparable to the yield from conventional method (1-20%) which requires -78 °C and 50 psi NO. Furthermore, the yield of this method is sufficient for chemical and biological assays.

Conclusion. This study proposed a possible alternative method for synthesizing cyclohexylamine NONOate using TiO2 catalysis at ambient conditions. Although the yield is lower than that of conventional method, the result is quite sufficient for chemical and biological assays. This approach eliminates the requirement of using specialized high-pressure and low-temperature equipment, making the study of HNO donors more feasible.

Supporting Agency

  • Mindanao State University-Iligan Institute of Technology, Philippines through the Office of the Vice-Chancellor for Research and Enterprise

Author Biographies

Nonil Mart S. Aque, Mindanao State University-Iligan Institute of Technology

Master of Science in Chemistry

Department of Chemistry

Maria Distressa G. Billacura, Mindanao State University-Iligan Institute of Technology

Doctor of Philosophy in Chemistry

Department of Chemistry

Merell P. Billacura, Mindanao State University-Main Campus, Marawi

Doctor of Philosophy in Chemistry

Department of Chemistry

Joel Jorolan, Mindanao State University-Iligan Institute of Technology

Doctor of Philosophy in Chemistry

Department of Chemistry

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TiO2-catalyzed synthesis of a primary amine NONOate

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Published

2026-04-30

How to Cite

Aque, N. M. S., Billacura, M. D. G., Billacura, M. P., & Jorolan, J. (2026). TiO2-catalyzed synthesis of a primary amine NONOate. ScienceRise: Pharmaceutical Science, (2 (60), 118–131. https://doi.org/10.15587/2519-4852.2026.342943

Issue

No. 2 (60) (2026)

Section

Pharmaceutical Science

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Copyright (c) 2026 Nonil Mart S. Aque, Maria Distressa G. Billacura, Merell P. Billacura, Joel Jorolan

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