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Article

Thermodynamics of Interactions of Water-Soluble Porphyrins with RNA Duplexes

Ara A. Ghazaryan,^† Yeva B. Dalyan,^† Samvel G. Haroutiunian,^† Anna Tikhomirova,^‡ Nicolas Taulier,^‡ James W. Wells,^‡ and Tigran V. Chalikian*^‡

Contribution from the Department of Molecular Physics, Faculty of Physics, Yerevan State University, 1 Alex Manoogian Street, Yerevan 375025, Armenia, and Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, 19 Russell Street, Toronto, Ontario M5S 2S2, Canada

J. Am. Chem. Soc., 2006, 128 (6), pp 1914–1921

DOI: 10.1021/ja054070n

Publication Date (Web): January 24, 2006

†

Yerevan State University.

‡

University of Toronto.

In papers with more than one author, the asterisk indicates the name of the author to whom inquiries about the paper should be addressed.

, chalikan@phm.utoronto.ca

Abstract

We characterized the interactions of meso-tetrakis(4N-(2-hydroxyethyl)pyridinium-4-yl) porphyrin (TEtOHPyP4), meso-tetrakis(4N-allylpyridinium-4-yl) porphyrin (TAlPyP4), and meso-tetrakis(4N-metallylpyridinium-4-yl) porphyrin (TMetAlPyP4) with the poly(rA)poly(rU) and poly(rI)poly(rC) RNA duplexes between 18 and 45 °C by employing circular dichroism, light absorption, and fluorescence intensity spectroscopic measurements. Our results suggest that TEtOHPyP4 and TAlPyP4 intercalate into the poly(rA)poly(rU) and poly(rI)poly(rC) host duplexes, while TMetAlPyP4 associates with these RNA duplexes by forming outside-bound, self-stacked aggregates. We used our temperature-dependent absorption titration data to determine the binding constants and stoichiometry for each porphyrin−RNA binding event studied in this work. From the temperature dependences of the binding constants, we calculated the binding free energies, ΔG_b, enthalpies, ΔH_b, and entropies, ΔS_b. For each RNA duplex, the binding enthalpy, ΔH_b, is the most favorable for TEtOHPyP4 (an intercalator) followed by TAlPyP4 (an intercalator) and TMetAlPyP4 (an outside binder). On the other hand, for each duplex, external self-stacking of TMetAlPyP4 produces the most favorable change in entropy, ΔS_b, followed by the intercalators TAlPyP4 and TEtOHPyP4. Thus, our results suggest that the thermodynamic profile of porphyrin−RNA binding may correlate with the binding mode. This correlation reflects the differential nature of molecular forces that stabilize/destabilize the two modes of bindingintercalation versus external self-stacking along the host duplex.