Ruthenium–Thymine Acetate Binding Modes: Experimental and Theoretical Studies

Ruthenium complexes have proved to exhibit antineoplastic activity, related to the interaction of the metal ion with DNA. In this context, synthetic and theoretical studies on ruthenium binding modes of thymine acetate (THAc) have been focused to shed light on the structure-activity relationship. Th...

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Main Authors: Silvia Bordoni, Stefano Cerini, Riccardo Tarroni, Magda Monari, Gabriele Micheletti, Carla Boga
Format: Article
Language:English
Published: MDPI AG 2021-03-01
Series:Applied Sciences
Subjects:
Online Access:https://www.mdpi.com/2076-3417/11/7/3113
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spelling doaj-3b7ef2d162cc4055807af3ab81e50e372021-03-31T23:06:51ZengMDPI AGApplied Sciences2076-34172021-03-01113113311310.3390/app11073113Ruthenium–Thymine Acetate Binding Modes: Experimental and Theoretical StudiesSilvia Bordoni0Stefano Cerini1Riccardo Tarroni2Magda Monari3Gabriele Micheletti4Carla Boga5Dipartimento di Chimica Industriale “Toso Montanari”, Università di Bologna, Viale Risorgimento 4, 40136 Bologna, ItalyDipartimento di Chimica Industriale “Toso Montanari”, Università di Bologna, Viale Risorgimento 4, 40136 Bologna, ItalyDipartimento di Chimica Industriale “Toso Montanari”, Università di Bologna, Viale Risorgimento 4, 40136 Bologna, ItalyDipartimento di Chimica “Giacomo Ciamician”, Università di Bologna, Via Selmi 2, 40126 Bologna, ItalyDipartimento di Chimica Industriale “Toso Montanari”, Università di Bologna, Viale Risorgimento 4, 40136 Bologna, ItalyDipartimento di Chimica Industriale “Toso Montanari”, Università di Bologna, Viale Risorgimento 4, 40136 Bologna, ItalyRuthenium complexes have proved to exhibit antineoplastic activity, related to the interaction of the metal ion with DNA. In this context, synthetic and theoretical studies on ruthenium binding modes of thymine acetate (THAc) have been focused to shed light on the structure-activity relationship. This report deals with the reaction between dihydride ruthenium mer-[Ru(H)<sub>2</sub>(CO)(PPh<sub>3</sub>)<sub>3</sub>], <b>1</b> and the thymine acetic acid (THAcOH) selected as model for nucleobase derivatives. The reaction in refluxing toluene between <b>1</b> and THAcOH excess, by H<sub>2</sub> release affords the double coordinating species κ<sup>1</sup>-(O)THAc-, κ<sup>2</sup>-(O,O)THAc-[Ru(CO)(PPh<sub>3</sub>)<sub>2</sub>], <b>2</b>. The X-ray crystal structure confirms a simultaneous monohapto, dihapto- THAc coordination in a reciprocal facial disposition. Stepwise additions of THAcOH allowed to intercept the monohapto mer-κ<sup>1</sup>(O)THAc-Ru(CO)H(PPh<sub>3</sub>)<sub>3</sub>] <b>3</b> and dihapto <i>trans</i><sub>(P,P)</sub>-κ<sup>2</sup>(O,O)THAc-[Ru(CO)H(PPh<sub>3</sub>)<sub>2</sub>] <b>4</b> species. Nuclear magnetic resonance (NMR) studies, associated with DFT (Density Function Theory)-calculations energies and analogous reactions with acetic acid, supported the proposed reaction path. As evidenced by the crystal supramolecular hydrogen-binding packing and <sup>1</sup>H NMR spectra, metal coordination seems to play a pivotal role in stabilizing the minor [(N=C(OH)] lactim tautomers, which may promote mismatching to DNA nucleobase pairs as a clue for its anticancer activity.https://www.mdpi.com/2076-3417/11/7/3113rutheniumthymine acetateX-ray crystal structureDFT-energy calculations<i>cis</i>-<i>trans</i> interconversionH-bonding intermolecular network
collection DOAJ
language English
format Article
sources DOAJ
author Silvia Bordoni
Stefano Cerini
Riccardo Tarroni
Magda Monari
Gabriele Micheletti
Carla Boga
spellingShingle Silvia Bordoni
Stefano Cerini
Riccardo Tarroni
Magda Monari
Gabriele Micheletti
Carla Boga
Ruthenium–Thymine Acetate Binding Modes: Experimental and Theoretical Studies
Applied Sciences
ruthenium
thymine acetate
X-ray crystal structure
DFT-energy calculations
<i>cis</i>-<i>trans</i> interconversion
H-bonding intermolecular network
author_facet Silvia Bordoni
Stefano Cerini
Riccardo Tarroni
Magda Monari
Gabriele Micheletti
Carla Boga
author_sort Silvia Bordoni
title Ruthenium–Thymine Acetate Binding Modes: Experimental and Theoretical Studies
title_short Ruthenium–Thymine Acetate Binding Modes: Experimental and Theoretical Studies
title_full Ruthenium–Thymine Acetate Binding Modes: Experimental and Theoretical Studies
title_fullStr Ruthenium–Thymine Acetate Binding Modes: Experimental and Theoretical Studies
title_full_unstemmed Ruthenium–Thymine Acetate Binding Modes: Experimental and Theoretical Studies
title_sort ruthenium–thymine acetate binding modes: experimental and theoretical studies
publisher MDPI AG
series Applied Sciences
issn 2076-3417
publishDate 2021-03-01
description Ruthenium complexes have proved to exhibit antineoplastic activity, related to the interaction of the metal ion with DNA. In this context, synthetic and theoretical studies on ruthenium binding modes of thymine acetate (THAc) have been focused to shed light on the structure-activity relationship. This report deals with the reaction between dihydride ruthenium mer-[Ru(H)<sub>2</sub>(CO)(PPh<sub>3</sub>)<sub>3</sub>], <b>1</b> and the thymine acetic acid (THAcOH) selected as model for nucleobase derivatives. The reaction in refluxing toluene between <b>1</b> and THAcOH excess, by H<sub>2</sub> release affords the double coordinating species κ<sup>1</sup>-(O)THAc-, κ<sup>2</sup>-(O,O)THAc-[Ru(CO)(PPh<sub>3</sub>)<sub>2</sub>], <b>2</b>. The X-ray crystal structure confirms a simultaneous monohapto, dihapto- THAc coordination in a reciprocal facial disposition. Stepwise additions of THAcOH allowed to intercept the monohapto mer-κ<sup>1</sup>(O)THAc-Ru(CO)H(PPh<sub>3</sub>)<sub>3</sub>] <b>3</b> and dihapto <i>trans</i><sub>(P,P)</sub>-κ<sup>2</sup>(O,O)THAc-[Ru(CO)H(PPh<sub>3</sub>)<sub>2</sub>] <b>4</b> species. Nuclear magnetic resonance (NMR) studies, associated with DFT (Density Function Theory)-calculations energies and analogous reactions with acetic acid, supported the proposed reaction path. As evidenced by the crystal supramolecular hydrogen-binding packing and <sup>1</sup>H NMR spectra, metal coordination seems to play a pivotal role in stabilizing the minor [(N=C(OH)] lactim tautomers, which may promote mismatching to DNA nucleobase pairs as a clue for its anticancer activity.
topic ruthenium
thymine acetate
X-ray crystal structure
DFT-energy calculations
<i>cis</i>-<i>trans</i> interconversion
H-bonding intermolecular network
url https://www.mdpi.com/2076-3417/11/7/3113
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