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


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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

  • Ashwood, B.; Ortiz-Rodríguez, L. A.; Crespo-Hernández, C. E., "Photochemical Relaxation Pathways of S6-Methylthioinosine and O6-Methylguanosine in Solution", Faraday Discuss. 2018, DOI: 10.1039/C7FD00193B. Invited Manuscript; submitted as part of the themed collection: "Photoinduced Processes in Nucleic Acids and Proteins". Access article
  • Pollum, M.; Minh, L.; Jockusch, S.; Crespo-Hernández, C. E., "Dithionated Nucleobases as Effective Photodynamic Agent Against Human Epidermoid Carcinoma Cells", 2018, to be submitted. Access article
  • Crespo-Hernández, C. E., "Photorelaxation and Photorepair Processes in Nucleic and Amino Acid Derivatives" (Editorial), Molecules 2017, 22, 2203. Access article
  • Ashwood, B.; Ortiz-Rodríguez, L. A.; Crespo-Hernández, C. E., "Excited-State Dynamics of O6-Methylguanosine: Impact of O6-Methylation on the Photophysics of Guanine Monomers", J. Phys. Chem. Lett. 2017, 8, 4380–4385. Access article
  • Sánchez-Rodríguez, J. A.; Mohamadzade, A.; Mai. S.; Ashwood, B.; Pollum, M.; Marquetand, P.; González, L.; Crespo-Hernández, C. E.; Ullrich, S., "2-Thiouracil Intersystem Crossing Photodynamics Studied by Wavelength-Dependent Photoelectron and Transient Absorption Spectroscopies", Phys. Chem. Chem. Phys. 2017, 19, 19756-19766. Invited Manuscript; submitted as part of the themed issue on the "XUV/XRay Light and Fast Ions for Ultrafast Chemistry".Access article
  • DiScipio, R.; Santiago, R. Y.; Taylor, D.; Crespo-Hernández, C. E., "Electronic Relaxation Pathways of the Biologically Relevant Pterin Chromophore", Phys. Chem. Chem. Phys. 2017, 19, 12720-12729. Access article
  • Mai, S.; Ashwood, B.; Marquetand, P; Crespo-Hernández, C. E.; González, L., "Solvatochromic Effects on the Absorption Spectrum of 2-Thiocytosine", J.Phys. Chem. B 2017, 121, 5187-5196. Access article
  • Ashwood, B.; Jockusch, S.; Crespo-Hernández, C. E., "Photochemical Reactivity of dTPT3: A Crucial Nucleobase Derivative in the Development of Semi-Synthetic Organisms", J. Phys. Chem. Lett. 2017, 8, 2387−2392. Access article
  • Ashwood, B.; Jockusch, S.; Crespo-Hernández, C. E., "Excited-State Dynamics of the Thiopurine Prodrug 6-Thioguanine: Can N9-Glycosylation Affects Its Phototoxic Activity?", Molecules 2017, 22, 379 (15 pages). Access article
  • Martínez-Fernández, L.; Granucci, G.; Pollum, M.; Crespo-Hernández, C. E.; Persico, M.; Corral, I., "Decoding the Molecular Basis for the Population Mechanism of the Triplet Phototoxic Precursors in UVA Light-Activated Pyrimidine Anticancer Drugs", Chem. Eur. J. 2017, 23, 2619-2627. Access article
  • Mai, S.; Pollum, M.; Martínez-Fernández, L.; Dunn, N.; Marquetand, P.; Corral, I.; Crespo-Hernández, C. E.; González, L., "The Origin of Efficient Triplet State Population in Sulfur-Substituted Nucleobases", Nature Commun. 2016, 7, 13077 (DOI: 10.1038/ncomms13077). Access article
  • Pollum, M.; Ashwood, B.; Jockusch, S.; Lam, M; Crespo-Hernández, C. E., "Unintended Consequences of Expanding the Genetic Alphabet", J. Am. Chem. Soc. 2016, 138, 11457-11460. Access article
  • Highlighted among other news media by:

    (1) American Chemical Society Office of Public Affairs’ Weekly Press PACs; (2) Nature magazine in Research Highlights; (3) Newswise An Expanded genetic code is shown phototoxic to cells; (4) PHYS.ORG Unintended consequences of creating the world's first semisynthetic organism; (5) MedicalResearch.com Expanded Genetic DNA more Susceptible to Ultraviolet Light Damage.

  • Ashwood, B.; Pollum, M.; Crespo-Hernández, C. E., "Can a Six-Letter Alphabet Increase the Likelihood of Photochemical Assault to the Genetic Code?", Chem. Eur. J. 2016, 22, 16648-16656. Access article
  • Yu, H. Sanchez-Rodriguez, J. A.; Ullrich, S.; Pollum, M.; Crespo-Hernández, C. E.; Mai. S.; Marquetand, P.; González, L., "Internal Conversion and Intersystem Crossing Pathways in UV Excited, Isolated Uracils and Their Implications in Prebiotic Chemistry", Phys. Chem. Chem. Phys. 2016, 18, 20168-20176. Invited Manuscript; submitted as part of the themed issue on the "Prebiotic Chemistry and the Molecular Origins of Life".Access article
  • Pollum, M.; Guan, L.; Ahsanuddin, S.; Baron, E.; Lam, M.; Crespo-Hernández, C., "Photoactivation of sulfur-modified DNA and RNA analogs induces cytotoxicity in epidermoid carcinoma cells", J. Invest. Dermatol. 2016, 136, S105. Access article
  • Brister, M.; Pollum, M.; Crespo-Hernández, C. E., "Photochemical Etiology of Promising Ancestors of the RNA Nucleobases", Phys. Chem. Chem. Phys. 2016, 18, 20097-20103. Invited Manuscript; submitted as part of the themed issue on the "Prebiotic Chemistry and the Molecular Origins of Life".Access article
    Highlighted in the journal's back cover image.
  • Pollum, M.; Ortiz-Rodríguez, L. A.; Jockusch, S.; Crespo-Hernández, C. E., "The Triplet State of 6-Thio-2’-deoxyguanosine: Intrinsic Properties and Reactivity toward Molecular Oxygen", Photochem. Photobiol. 2016, 92, 286-292. Access article
  • Selected as one of the top papers published in the journal Photochemistry & Photobiology, as part of a virtual issue cellebrating its 55th anniversary.
    Access and read the complete virtual issue here.
  • Brister, M.; Crespo-Hernández, C. E. "Direct Observation of Triplet-State Population Dynamics in the RNA Uracil Derivative 1-Cyclohexyluracil", J. Phys. Chem. Lett. 2015, 6, 4404-4409. 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
  • 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-Hernández, 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-Hernández, 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-Hernández, C. E.; "Ultrafast Spin Crossover in 4-Thiothymidine in an Ionic Liquid", Chem. Comm. 2010, 46, 5963-5965.Access article