Exactly How Does TLD1433 Kill Cancer Cells?Dr. McFarland intends to spend the next 3 years finding out, financed by an NSF award of $440,000.
"...insight regarding the potential photobiological mechanism(s) of TLD1433 and related PSs could lead to the development of Ru(II) photodrugs with even better properties than TLD1433." Restricted Research - Award List, Note/Discussion Page Restricted Research - Award List, Note/Discussion Page
Fiscal Year: 2021
1330 The University of Texas at Arlington (85626)
Principal Investigator: Sherri McFarland
Total Amount of Contract, Award, or Gift (Annual before 2011): $ 440,000
Exceeds $250,000 (Is it flagged?): Yes
Start and End Dates: 8/1/21 - 7/31/24
Restricted Research: New/Blank/Unresolved/Undetermined
Academic Discipline: College of Science
Department, Center, School, or Institute: Department of Chemistry and Biochemistry
Title of Contract, Award, or Gift: The Excited State Behavior of Ru(II) Photodrugs
Name of Granting or Contracting Agency/Entity: National Science Foundation (NSF)
CFDA Link: NSF
47.049
Program Title: Division of Chemistry: Disciplinary Research Programs (CHE-DRP)
CFDA Linked: Mathematical and Physical Sciences
Note:
The project will examine the excited state behavior of our TLD1433 and related Ru(II) photodrugs. We propose a new mechanism that may account for the very high photocytotoxicity that certain oligothiophene-containing Ru(II) photodrugs show toward cancer cells, both in normoxia and in hypoxia. The project also aims to develop the photophysical model(s) for these photosensitizers (PSs) in complex biological environments. More broadly, this work will generate new knowledge about the relationships between molecular structure, redox chemistry and photophysics, and potentially novel photocytotoxic mechanisms. This insight regarding the potential photobiological mechanism(s) of TLD1433 and related PSs could lead to the development of Ru(II) photodrugs with even better properties than TLD1433. Obj 1: We will synthesize and characterize oligothiophene-appended Ru(II) PSs, [Ru(LL)2(IP-nT)]2+, that differ in the number of thiophene rings (nT), the types of substituents on the thiophene rings, and the coligands (LL). The modifications are designed to vary redox potentials and triplet state characteristics and to alter the covalent and noncovalent associations typical of oligothiophenes. Obj 2: Electrochemical techniques will be used to test the hypothesis that the Ru(II) PSs can participate in biological photoredox catalysis, where biomolecules can be oxidized (or reduced) by a catalytic PS* with or without oxygen. The purpose is to show that photoredox catalysis is possible using simple biological substrates. (SAM Category: 1.1.1)