Molecular Optical Diagnostic Probes: Rationally Designed Quinolines with Raman-Chiral-Fluorescent Activity

Molecular theranostic agents, due to their subnanometersize, havethe advantage of long blood circulation times, leading to better targetingefficiency with minimal injected dosages. To that end, quinoline derivativesare attractive as drugs and are being explored for cancer therapy.Therefore, structurally adapting and repurposing them for use in diagnosiswould improve disease-site targeting significantly. In this study,we report a strategic modification of the quinoline and quinolinefragment nicotinamide and demonstrate their diagnostic capabilities.The molecular design strategically incorporates a pyridine ring withcysteine functionalization specifically at position 3, along withthiol and carboxyl end groups. The synthesized molecules demonstratedstrong fluorescence and chiroptical activities. When functionalizedonto gold nanostructures, the surface-enhanced Raman scattering (SERS)of the synthesized molecules was similar to a commercial quinolinethiol Raman probe. The strong Raman-chiral-fluorescence optical activityof the molecules is promising for their use as multimodal diagnosticprobes. In contrast to the commercially available quinoline thiol,the synthesized derivatives featured higher cell viability in bothhealthy and cancerous human cells and a potential to selectively killcancer cells without negatively impacting the growth of the surroundinghealthy ones. The reported work thus showcases custom-designed moleculeswith multimodal functionality of biocompatibility, fluorescence, chirality,Raman activity, and potential for cancer-selective therapy, enablingwider applicability in cancer theranostics.

Automated summary

This study reports the strategic modification of quinoline and quinoline derivative nicotinamide, as well as their potential in diagnosis. The synthesized molecules showed strong fluorescence and chiroptical activities when functionalized onto gold nanostructures, with similar surface-enhanced Raman scattering (SERS) to a commercial quinoline thiol Raman probe. Unlike the commercially available quinoline thiol, the synthesized derivatives exhibited higher cell viability in both healthy and cancerous cells, and selectively killed cancer cells without negatively impacting healthy cells. This work highlights the potential of custom-designed molecules with multimodal functionality for wider applicability in cancer theranostics.