Fine-tuning physicochemical properties of Oxazine-4 for nerve-specific imaging

Accidental damage of vital nerve structures remains a significant surgical morbidity. Patient-to-patient neuroanatomical variability requires considerable dependence on a surgeon’s first-hand experiences that primarily rely on proximal features for orientation, which can be further complicated in patients with nerve damage. As such, enhanced nerve visualization proves to be a vital avenue for advancing surgical precision and patient outcomes. Fluorescence guided surgery (FGS) has the potential to improve surgical guidance, but there are no current nerve-specific fluorophores approved for clinical use. Previous work has identified the oxazine scaffold as a promising avenue for nerve-specific contrast agent development, due to its sufficiently low molecular weight to cross the blood-nerve-barrier (BNB), tunable photophysical properties, and high nerve specificity. Herein we report our efforts to investigate the structure-function relationship of Oxazine-4 through fine-tuned terminal alkylamino modifications, both based on optical and physicochemical properties as well as their affected nerve specificities.