SLAC researchers are developing a new light-activated method to produce nitrosoxide molecules, which opens the door to future biomedical applications. Scientists at the U.S. Department of Energy's SLAC National Accelerator Laboratory have gained valuable insights into the production of nitric oxide, a molecule with potential applications in biomedicine.
Researchers used advanced X-ray spectroscopy techniques at SLAC's Stanford Synchrotron Radiation Lightsource (SSRL) to delve deeper into the chemical properties of nitroxide. Source: Greg Stewart/SLAC National Accelerator Laboratory
While nitric oxide (NO) has long attracted the attention of researchers due to its significant physiological effects, its lesser-known cousin, hyponitrite (HNO), remains largely unexplored.
The research, recently published in the Journal of the American Chemical Society, is the result of a joint effort between teams at SLAC's Linear Coherent Light Source (LCLS) X-ray laser and the Stanford Synchrotron Radiation Lightsource (SSRL).
Nitric acid has many of the same physiological effects as nitric oxide, such as fighting germs, preventing blood clots, relaxing and dilating blood vessels, etc., while also having additional therapeutic properties, such as efficacy in treating heart failure, as well as stronger antioxidant activity and wound healing capabilities. However, it is not a chemically long-lived substance, so methods that can deliver it directionally are key for future biomedical applications.
To address this challenge, the research team focused on a unique molecule - iron-nitroso complex (Fe-NO). Their research aimed to understand the complex nature of the Fe-NO bond before and after light irradiation to understand the complexity of nitrosyl generation. They found that exposing the molecule to optical light could break its bonds, potentially producing nitrosoxides.
"While this research is fundamental, we hope that other researchers will be able to use what we learn from this molecule to build therapeutic technologies by optimizing similar pharmaceutical molecules," said SLAC scientist and collaborator Leland Gee. "The idea is to get a molecule that releases HNO where it's needed in the body and irradiate it so that it releases its therapeutic properties."
One of the challenges the research team faced was the unclear distribution of electrons between the iron atoms and the nitroso ligand (a molecule or ion that binds to the central metal atom or ion) in the iron-NO complex, which limited the amount of information that could be obtained using traditional methods. The scientists employed advanced X-ray spectroscopy techniques at SSRL, allowing them to delve deeper into the chemistry of the molecules and their bonds, resulting in a more complete understanding of the Fe-NO system and its response to light.
In follow-up work, the scientists plan to further explore the complexity of the bond-breaking process and how to optimize the production of nitrate oxide or nitric oxide. They are also considering replacing the iron with other metals to better understand the photogeneration process.
"In this study, we understand the starting molecules and their end products after illumination," Gee said. "There are still many nuances to explore in the process of actually breaking the bond and releasing nitroxide from the molecule. Which step in the process determines the release of nitric oxide? How can we structurally tailor the system to produce either molecule?"
This work helps understand which properties need to be monitored in future experiments at LCLS, where scientists will be able to take snapshots of the nitric oxide light-generating process in real time.
"The information we obtained highlights the power of this approach and provides a blueprint for future studies of these and similar molecules at LCLS," Gee said.
This research raises hope for the medical community and patients, who may benefit from future applications.
"While we are still far away from harnessing the light of these molecules to treat severe cardiovascular disease, a basic understanding of these molecules provides a solid foundation for future applied research," Gee said. "This could lead to entirely new ways to use light to treat cardiovascular disease, microbial infections, cancer and other health problems."