Near-Infrared Fluorescent Rosol Dye Tailored toward Lymphatic Mapping Applications.

An optical molecular imaging contrast agent that is tailored toward lymphatic mapping techniques implementing near-infrared (NIR) fluorescence image-guided navigation in the planning and surgical treatment of cancers would significantly aid in enabling the real-time visualization of the potential metastatic tumor-draining lymph node(s) for their needed surgical biopsy and/or removal, thereby ensuring unmissed disease to prevent recurrence and improve patient survival rates. Here, the development of the first NIR fluorescent rosol dye (THQ-Rosol) tailored to overcome the limitations arising from the suboptimal properties of the generic molecular fluorescent dyes commonly used for such applications is described. In developing THQ-Rosol, we prepared a progressive series of torsionally restrictive N-substituted non-NIR fluorescent rosol dyes based on density functional theory (DFT) calculations, wherein we discerned high correlations amongst their calculated energetics, modeled N-C3' torsion angles, and evaluated properties. We leveraged these strong relationships to rationally design THQ-Rosol, wherein DFT calculations inspired an innovative approach and synthetic strategy to afford an uncharged xanthene core-based scaffold/molecular platform with an aptly elevated p K