SLAC Scientists Illuminate Breakthrough Biomedical Molecule

SLAC

Scientists from the Department of Energy's SLAC National Accelerator Laboratory have gained valuable insights into producing nitroxide, a molecule with potential applications in the biomedical field. While nitric oxide (NO) has long been on researchers' radar for its significant physiological effects, its lesser-known cousin, nitroxide (HNO), has remained largely unexplored.

The study, published recently in the Journal of the American Chemical Society, was born out of a joint endeavor between teams at SLAC's Linac Coherent Light Source (LCLS) X-ray laser and Stanford Synchrotron Radiation Lightsource (SSRL).

Nitroxide has many of the same physiological effects of nitric oxide - such as its ability to fight germs, prevent blood clots, and relax and dilate blood vessels - with additional therapeutic properties, such as efficacy in treating heart failure, as well as more potent antioxidant activity and wound healing. However, it is not a chemically long-lived species so methods that enable its targeted delivery are key to future biomedical applications.

To address this challenge, the team focused on a unique molecule, an iron-nitrosyl complex (Fe-NO). Their research aimed to understand the intricate properties of the Fe-NO bond, both before and after light exposure, to navigate the complexities of nitroxide production. They discovered that by exposing this molecule to optical light, they could break its bond, potentially producing nitroxide.

"Although this research is fundamental in nature, the hope is that other researchers can take what we learn from this molecule and build therapeutic technologies off of it by optimizing similar molecules for medicine," said SLAC scientist and collaborator Leland Gee. "The idea would be to get a molecule that releases HNO in the body where it is needed and shine light on it to release it for the therapeutic properties."

One of the challenges the team faced was the ambiguous distribution of electrons between the iron atom and the nitrosyl ligand - a molecule or ion that binds to a central metal atom or ion - in the Fe-NO complex, which limits how much information can be gained using traditional methods. The scientists employed advanced X-ray spectroscopic techniques at SSRL that allowed them to peer deeper into the chemical properties of the molecule and its bond, providing a more complete picture of the Fe-NO system and how it responds to light.

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