APPLIED ORGANIC CHEMISTRY

Our interests in applied organic chemistry are in the general area of the use of fluorescent organic compounds - especially the 4-amino-1,8-naphthalimides - as agents for applications in medicine, histopathology, and engineering. Our work in applied organic chemistry continues to involve compounds based on the highly fluorescent 4-amino-1,8-naphthalimide carbon skeleton

MEDICAL APPLICATIONS OF CHEMISTRY

Our earliest work in this area involved the inactivation of enveloped pathogens by visible light. Many biological entities, including enveloped viruses (e.g. herpes viruses and the HIV retrovirus), are surrounded by a lipid bilayer membrane. We succeeded in obtaining brominated, dimeric naphthalimide dyes that showed exceptional promise for use as photochemically-activated anti-herpes and anti-HIV compounds in vitro. These dyes not only inhibited infection of healthy cells by cell-free HIV-1 in vitro, but also inhibited syncytium formation with healthy cells by HIV-1-infected cells. The continuation of this work was taken up by our collaborators in photobiology.


More hydrophilic versions of the dye, lacking the halogen, proved to be excellent compounds for the photochemical welding of tissues using blue (i.e. visible) laser light. Healing studies of welds in sheep articular cartilage indicated that these dyes have excellent potential for use as adjuncts for orthopedic surgery. This project is being continued by our collaborators in photobiology and orthopedic surgery.



More recently, we have found that the 4-alkylamino-1,8-naphthalimide nucleus provides an excellent scaffold on which to construct a variety of site-selective probes for fluorescence microscopy. These dyes are easily delivered to the cell, sequester rapidly, and in a highly selective way in the target organelle, and, in the absence of intense laser light, are non-toxic, allowing their use in live cells. Importantly, these dyes do not undergo rapid photochemical bleaching under normal epifluorescence illumination. At present, these dyes are available for the observation of lysosomes, mitochondria, Golgi body and its associated transport vesicles, and high-cholesterol or other highly ordered microdomains of membranes.


ENGINEERING APPLICATIONS OF ORGANIC CHEMISTRY

In the late 1990's, we discovered a class of naphthalimides where the fluorescence of the naphthalimide fluorophore is quenchedby photoexcited electron transfer involving the distal amino nitrogen atom. On complexation with the metal ion, this quenching mechanism is eliminated, and quenching of the fluorescence by the metal ion becomes the dominant quenching mechanism. This is one of the few known cases where quenching by a lone pair is more efficient than quenching by a paramagnetic metal ion.


Based upon this unique property, we have now developed a new fluorescence-based analytical procedure which can be used for the non-destructive analysis of wear metals in non-aqueous systems, including lubricants. The procedure is especially sensitive for copper (II) ion, allowing its detection at the sub-ppm level.