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Good Vibrations Report on the DNA Quadruplex Binding of an Excited State Amplified Ruthenium Polypyridyl IR Probe

[Image: see text] The nitrile containing Ru(II)polypyridyl complex [Ru(phen)(2)(11,12-dCN-dppz)](2+) (1) is shown to act as a sensitive infrared probe of G-quadruplex (G4) structures. UV–visible absorption spectroscopy reveals enantiomer sensitive binding for the hybrid htel(K) and antiparallel htel...

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Autores principales: Stitch, Mark, Avagliano, Davide, Graczyk, Daniel, Clark, Ian P., González, Leticia, Towrie, Michael, Quinn, Susan J
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2023
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10557146/
https://www.ncbi.nlm.nih.gov/pubmed/37736878
http://dx.doi.org/10.1021/jacs.3c06099
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author Stitch, Mark
Avagliano, Davide
Graczyk, Daniel
Clark, Ian P.
González, Leticia
Towrie, Michael
Quinn, Susan J
author_facet Stitch, Mark
Avagliano, Davide
Graczyk, Daniel
Clark, Ian P.
González, Leticia
Towrie, Michael
Quinn, Susan J
author_sort Stitch, Mark
collection PubMed
description [Image: see text] The nitrile containing Ru(II)polypyridyl complex [Ru(phen)(2)(11,12-dCN-dppz)](2+) (1) is shown to act as a sensitive infrared probe of G-quadruplex (G4) structures. UV–visible absorption spectroscopy reveals enantiomer sensitive binding for the hybrid htel(K) and antiparallel htel(Na) G4s formed by the human telomer sequence d[AG(3)(TTAG(3))(3)]. Time-resolved infrared (TRIR) of 1 upon 400 nm excitation indicates dominant interactions with the guanine bases in the case of Λ-1/htel(K), Δ-1/htel(K), and Λ-1/htel(Na) binding, whereas Δ-1/htel(Na) binding is associated with interactions with thymine and adenine bases in the loop. The intense nitrile transient at 2232 cm(–1) undergoes a linear shift to lower frequency as the solution hydrogen bonding environment decreases in DMSO/water mixtures. This shift is used as a sensitive reporter of the nitrile environment within the binding pocket. The lifetime of 1 in D(2)O (ca. 100 ps) is found to increase upon DNA binding, and monitoring of the nitrile and ligand transients as well as the diagnostic DNA bleach bands shows that this increase is related to greater protection from the solvent environment. Molecular dynamics simulations together with binding energy calculations identify the most favorable binding site for each system, which are in excellent agreement with the observed TRIR solution study. This study shows the power of combining the environmental sensitivity of an infrared (IR) probe in its excited state with the TRIR DNA “site effect” to gain important information about the binding site of photoactive agents and points to the potential of such amplified IR probes as sensitive reporters of biological environments.
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spelling pubmed-105571462023-10-07 Good Vibrations Report on the DNA Quadruplex Binding of an Excited State Amplified Ruthenium Polypyridyl IR Probe Stitch, Mark Avagliano, Davide Graczyk, Daniel Clark, Ian P. González, Leticia Towrie, Michael Quinn, Susan J J Am Chem Soc [Image: see text] The nitrile containing Ru(II)polypyridyl complex [Ru(phen)(2)(11,12-dCN-dppz)](2+) (1) is shown to act as a sensitive infrared probe of G-quadruplex (G4) structures. UV–visible absorption spectroscopy reveals enantiomer sensitive binding for the hybrid htel(K) and antiparallel htel(Na) G4s formed by the human telomer sequence d[AG(3)(TTAG(3))(3)]. Time-resolved infrared (TRIR) of 1 upon 400 nm excitation indicates dominant interactions with the guanine bases in the case of Λ-1/htel(K), Δ-1/htel(K), and Λ-1/htel(Na) binding, whereas Δ-1/htel(Na) binding is associated with interactions with thymine and adenine bases in the loop. The intense nitrile transient at 2232 cm(–1) undergoes a linear shift to lower frequency as the solution hydrogen bonding environment decreases in DMSO/water mixtures. This shift is used as a sensitive reporter of the nitrile environment within the binding pocket. The lifetime of 1 in D(2)O (ca. 100 ps) is found to increase upon DNA binding, and monitoring of the nitrile and ligand transients as well as the diagnostic DNA bleach bands shows that this increase is related to greater protection from the solvent environment. Molecular dynamics simulations together with binding energy calculations identify the most favorable binding site for each system, which are in excellent agreement with the observed TRIR solution study. This study shows the power of combining the environmental sensitivity of an infrared (IR) probe in its excited state with the TRIR DNA “site effect” to gain important information about the binding site of photoactive agents and points to the potential of such amplified IR probes as sensitive reporters of biological environments. American Chemical Society 2023-09-22 /pmc/articles/PMC10557146/ /pubmed/37736878 http://dx.doi.org/10.1021/jacs.3c06099 Text en © 2023 The Authors. Published by American Chemical Society https://creativecommons.org/licenses/by/4.0/Permits the broadest form of re-use including for commercial purposes, provided that author attribution and integrity are maintained (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Stitch, Mark
Avagliano, Davide
Graczyk, Daniel
Clark, Ian P.
González, Leticia
Towrie, Michael
Quinn, Susan J
Good Vibrations Report on the DNA Quadruplex Binding of an Excited State Amplified Ruthenium Polypyridyl IR Probe
title Good Vibrations Report on the DNA Quadruplex Binding of an Excited State Amplified Ruthenium Polypyridyl IR Probe
title_full Good Vibrations Report on the DNA Quadruplex Binding of an Excited State Amplified Ruthenium Polypyridyl IR Probe
title_fullStr Good Vibrations Report on the DNA Quadruplex Binding of an Excited State Amplified Ruthenium Polypyridyl IR Probe
title_full_unstemmed Good Vibrations Report on the DNA Quadruplex Binding of an Excited State Amplified Ruthenium Polypyridyl IR Probe
title_short Good Vibrations Report on the DNA Quadruplex Binding of an Excited State Amplified Ruthenium Polypyridyl IR Probe
title_sort good vibrations report on the dna quadruplex binding of an excited state amplified ruthenium polypyridyl ir probe
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10557146/
https://www.ncbi.nlm.nih.gov/pubmed/37736878
http://dx.doi.org/10.1021/jacs.3c06099
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