Development of Photoreactive Organic Compounds with Large Two-Photon Absorption Cross Sections

Date of Award


Document Type


Degree Name

Doctor of Philosophy (Ph.D.)


Photochemical Sciences

First Advisor

Vladimir Popik


The natural enediynes are the most potent antitumor-pharmacophores ever discovered. The high biological activity of these antineoplastic agents is due to a (Z)-3-ene-1,5-diyne moiety that undergoes Bergman cycloaromatization when activated chemically or photochemically. The clinical application of enediynes is limited because of their modest selectivity for cancer cells. Numerous approaches have been developed to increase selectivity and to control reactivity of enediyne antibiotics. However, in spite of intensive research over the past decade, a safe enediyne-based drug has yet to be developed. To address the issue of selectivity we have explored the approach of controlling reactivity of natural enediynes using methods of photodynamic therapy. There are several ways of generating reactive 9- or 10-membered cyclic enediynes. One is to start with a stable 11-membered enediyne and photochemically initiate ring contraction. This can be achieved via photo-Wolff reaction of α-diazocarbonyl-incorporated cyclic enediynes. Another method is to generate one or both triple bonds of the enediyne framework in situ. Photodecarbonylation of a cyclopropenone-incorporated 10-membered cyclic enediyne-precursor is a suitable reaction for this approach. In photo-triggering of either of these photoreactions one must consider the depth or light penetration into mammalian tissues and the cytotoxic effects of UV-Vis light. The greatest depth of light penetration into human soft tissues is achieved in the region of the so called phototherapeutic window extending between 650 and 950 nm. Luckily this range corresponds to the region of lowest light cytotoxicity. However, there is no spectral overlap between linear absorption of photoreactive substrate and NIR light. In order to photolytically trigger photoreaction one must use NIR light of high flux. The feasibility of two-photon induced photo-Wolff reaction was proven using 800 nm light of a Ti:sapphire laser reacting with diazonaphthoquinone 2.14. It is known that alkyl- or aryl-substituted cyclopropenones are thermally stable photoreactive compounds that undergo decarbonylation upon excitation with UV light. The feasibility of two-photon induced photodecarbonylation was demonstrated using cyclopropenone 3.23. Two-photon absorption properties of previously studied model α-diazocarbonyl- and cyclopropenone containing chromophores were relatively low. To determine the feasibility of two-photon absorption cross section enhancement of such chromophores we synthesized a series of symmetrical aryl-cyclopropenones 4.1-4.3 and 2-diazo-1,3-diketones 4.4 and 4.5 designed based on Donor- π-Acceptor-π-Donor structure. Two-photon absorption cross sections of 4.1-4.5 were determined using photochemical and white-light continuum probe methods. Experimental values of two-photon absorption cross sections of 4.1-4.5, although somewhat variable depending on the method employed, were generally in good agreement with one another. There was no direct correlation between two-photon absorption cross-section and the total area of a π-conjugated system of photoreactive substrates we studied. A better correlation was observed between two-photon absorption cross-section and the extinction coefficient at 400 nm. 2-diazo-1,3-diketone 4.5 possesses one of the highest reported two-photon absorption cross section, i.e. 440 GM, among photoreactive compounds. In summary, enhanced of two-photon absorption cross sections were achieved using photoreactive organic molecules 4.1-4.5.