Department of Chemistry

Current Group Research

Excited-State Dynamics of UVA Sensitizers and DNA Analogues

The focus of our research group is on identifying and studying DNA and RNA monomer analogues that exhibit high triplet yields. Excited triplet states are important precursor of light-induced DNA damage. However, progress at understanding the kinetic mechanisms by which triplet state is populated has been hindered by the intrinsically small triplet quantum yields of DNA and RNA monomers in aqueous solutions. Efforts at understanding the mechanisms by which triplet states are populated in DNA/RNA analogues can provide important information about the electronic and nuclear relaxation pathways that control the population of the triplet state in DNA monomers.

We are currently interested in a family of biomolecules known as prodrugs, which are widely use in therapeutic and pharmacological applications. Their metabolic incorporation into the DNA of patients treated with these prodrugs often results in increased toxicity and skin cancer after the patients are exposed to prolonged periods of sunlight. Understanding the excited-state dynamics in these DNA/RNA analogues can help to understand the light-induced chemistry in DNA/RNA monomers and it is also an important step toward the design of the next generation of prodrugs showing reduced phototoxic side effects.

2,4-Dithiothymine and 2,4-Dithiouracil as Potent UVA Chemotherapeutic Agents


Figure legend: Researchers in the laboratory of Carlos E. Crespo-Hernández in the Chemistry Department at Case Western Reserve University have recently revealed highly reactive DNA and RNA pyrimidine analogues showing more than 100 nm shift in absorption relative to their natural counterparts. Near-visible light-absorption by these sulfur-substituted nucleobases (a.k.a. thiobases) results in the formation of long-lived, reactive triplet states in yields that approach 100%. This is up to sixty four fold higher than the parent thymine and uracil nucleobases. The reactive triplet state can subsequently produce singlet oxygen in about 50% yield—among the highest yield reported thus far for any thiobase derivative. The fundamental results of this investigation are being used to develop DNA- and RNA-targeting compounds for light-activated therapeutics and for photocrosslinking structural biology investigations. Through an ongoing collaboration with researchers in the CWRU School of Medicine, the Crespo team led by graduate student Marvin Pollum has recently demonstrated the potential of doubly-substituted DNA and RNA thiobases to kill skin cancer cell lines upon activation by near-visible light. Detailed mechanistic investigations of the specific reactions of these thiobases with cancerous cells are expected to enable the development of the next generation of light-activated sensitizers for clinical applications.

Literature Recipes For Calculating Extinction Coefficients and Other Physical Properties of Short Oligonucleotides and DNA

In this webpage you can find a compilation of online methods for calculating extinction coefficients, melting temperatures and other physical properties of oligonucleotides and DNA. The last time this complilation was updated was in 12/08/2002, but it is still useful.

Recent Publications

  • Crespo-Hernández, C. E.; Martínez-Fernández, L.; Rauer, C.; Reichardt, C.; Mai, S.; Pollum, M.; Marquetand, P.; González, L.; Corral, I. "Electronic and Structural Elements that Regulate the Excited-State Dynamics in Purine Nucleobase Derivatives", J. Am. Chem. Soc. 2015, 137, 4368-4381. Access article
  • Pollum, M.; Martínez-Fernández, L.; Crespo-Hernández, C. E.; "Photochemistry of Nucleic Acid Bases and their Thio- and Aza-Analogues in Solution", Top. Curr. Chem. 2015, 355, 245-327. Invited Review Chapter. Access article
  • Pollum, M.; Jockusch, S.; Crespo-Hernández, C. E. "Increase in the Phooreactivity of Uracil Derivatives by Doubling Thionation", Phys. Chem. Chem. Phys. 2015, 17, 27851-27861. Access article
  • Pollum, M.; Jockusch, S.; Crespo-Hernández, C. E.; "2,4-Dithiothymine as a Potent UVA Chemotherapeutic Agent", J. Am. Chem. Soc. 2014, 136, 17930-17933. Access article
  • Pollum, M.; Crespo-Hernández, C. E.; "Communication: The dark singlet state as a doorway state in the ultrafast and efficient intersystem crossing dynamics in 2-thiothymine and 2-thiouracil", J. Chem. Phys. 2014, 140, 071101. Access article
  • Reichardt, C.; Wen, C.; Vogt, R. A.; Crespo-Hernández, C. E.; "Role of Intersystem Crossing in the Fluorescence Quenching of 2-Aminopurine 2'-deoxyriboside in Solution", Photochem. Photobiol. Sci. 2013, 12, 1341-1350. Invited Manuscript; submitted as part of the themed issue on the "Interaction of UV Radiation with DNA". Access article
  • Reichardt, C.; Guo, C.; Crespo-Hern�ndez, C. E.;"Excited-State Dynamics in 6-Thioguanosine from the Femtosecond to Microsecond Time Scale", J. Phys. Chem. B 2011, 115, 3263-3270.Access article
  • Reichardt, C.; Crespo-Hern�ndez, C. E.; "Room-Temperature Phosphorescence of the DNA Monomer Analogue 4-Thiothymidine in Aqueous Solutions after UVA Excitation", J. Phys. Chem. Lett. 2010, 1, 2239-2243.Access article
  • Reichardt, C.; Crespo-Hern�ndez, C. E.; "Ultrafast Spin Crossover in 4-Thiothymidine in an Ionic Liquid", Chem. Comm. 2010, 46, 5963-5965.Access article