Photochemical reactions of trans-[Ru(NH3)4L(NO)]3+ complexes

doi:10.1016/j.ica.2003.11.023

Inorganica Chimica Acta

Volume 357, Issue 5, 25 March 2004, Pages 1381-1388

https://doi.org/10.1016/j.ica.2003.11.023 Get rights and content

Abstract

The photochemical behavior of a series of trans-[Ru(NH₃)₄L(NO)]³⁺ complexes, where L=nitrogen bound imidazole, L-histidine, 4-picoline, pyridine, nicotinamide, pyrazine, 4-acetylpyridine, or triethylphosphite is reported. In addition to ligand localized absorption bands (<300 nm), the electronic spectra of these complexes are dominated by relatively low intensity bands assigned as ligand field (LF) and metal to ligand (d_π → NO) charge transfer (MLCT) transitions. Irradiation of aqueous solutions of these complexes with near-UV light (300–370 nm) labilizes NO, i.e., $trans - [Ru (NH_{3})_{4} L (NO)]^{3+} → hν [Ru (NH_{3})_{4} L (H_{2} O)]^{3+} + NO$ Quantum yields for [Ru(NH₃)₄L(H₂O)]³⁺ formation (φ_Ru(III)) are sensitive to the natures of L, λ_irr and pH. The lowest quantum yields (λ_irr=310 nm) were found for L = imidazole (0.03) and L-histidine (0.04), while much higher values were found for L=P(OEt)₃ (0.30). Irradiation at longer wavelengths does not induce photochemical reactivity. These results are interpreted in terms of the expected reactivities of d_π → NO MLCT state in these systems.

Irradiation of aqueous solutions of trans-[Ru(NH₃)₄L(NO)]³⁺ (L=pyridine derivative, pyrazine, or triethylphosphite) with light (300–370 nm) results in trans-[Ru(NH₃)₄L(H₂O)]³⁺ and NO as the only products. Irradiation at longer wavelengths does not result in observable photochemistry. Quantum yields (φ_Ru(III)) are sensitive to the nature of L, λ_irr and pH. The results suggest that a Ru d_π → NO metal to ligand charge transfer state is responsible for the observed photochemical reactions.

Introduction

It is now well recognized that nitric oxide (also known as nitrogen monoxide) has important roles in mammalian biology. It serves as a bioregulator of blood pressure, as a neurotransmitter and as a toxic agent formed in immune response to pathogens among other roles [1]. The initial studies have led to a plethora of studies concerning other possible biological roles for NO. Also of interest are the interactions of NO and related species with biologically important targets, the search for nitric oxide scavengers, and the design of compounds for therapeutic NO delivery from different donors, thermally or through activation with light [2], [3], [4], [5], [6], [7], [8], [9], [10], [11], [12], [13], [14], [15], [16], [17].

In the last context, the chemical and photochemical reactions of various metal nitrosyl complexes and of related species are being investigated [6], [7], [8], [9], [10], [11], [12], [13], [14], [15], [16], [17] with the goal of developing models for NO delivery agents in pharmaceutical applications. The physiological functions of NO are complicated and depend on thermodynamic, kinetic, and concentration considerations [2](a), [2](b), and high or low NO concentrations can be either beneficial or harmful; depending on the specific circumstances. Thus, there is a continuing need for controlled and site specific NO scavengers and NO delivery agents. As a consequence, there is considerable interest in stable compounds that can, with minimal toxic effects, release NO in vivo. In this context, water soluble ruthenium am(m)ine nitrosyls provide the basis for a systematic study and are shown to have tunable reactivities toward NO release [8], [9], [10], [11], [12], [13]. Recent in vivo experiments demonstrated that these are able to release NO after being reduced biologically, resulting in blood pressure suppression. Furthermore, these ruthenium complexes were less toxic than sodium nitroprusside, which is an NO donor used as a vasodilator in hypertensive emergencies [15], [16], [17].

Although other ruthenium nitrosyl and related complexes have been studied as potential NO delivery agents, there has been little systematic study of a series of related compounds in this regard. The trans-[Ru(NH₃)₄L(NO)]³⁺ complexes constitute a system where L can be systematically varied in order to tune the desired NO properties [8], [9], [10], [11], [12], [13], [14], [15], [16], [17]. Such an investigation can contribute to the fundamental understanding necessary to design systems with tunable thermal and photochemical properties for specific applications.

Preliminary photochemical experiments have shown that aqueous solutions of certain trans-[Ru(NH₃)₄L(NO)]³⁺complexes are photoactive toward near-UV excitation to give trans-[Ru(NH₃)₄L(H₂O)]³⁺ and NO as products [8], [9]: $trans - [Ru (NH_{3})_{4} L (NO)]^{3+} → hν trans - [Ru (NH_{3})_{4} L (H_{2} O)]^{3+} + NO$ This article describes the photochemical properties of the trans-[Ru(NH₃)₄L(NO)]³⁺ complexes where L is nitrogen bound imidazole (imN), L-Histidine (L-Hist), 4-picoline (4-pic), pyridine (py), 4-acetylpyridine (4-acpy), pyrazine (pz), nicotinamide (nic), and triethylphosphite (P(OEt)₃).

Section snippets

Materials and reagents

Ruthenium trichloride (RuCl₃ · nH₂O) (Strem or Aldrich) was the starting material for ruthenium complex syntheses. HPLC grade solvents were used, except acetone, ethyl ether and ethanol, which were purified according to the literature [18]. Doubly distilled water was used throughout. All other materials were reagent grade. The Ru(II) complexes trans-[Ru(NH₃)₄L(NO)]³⁺ (L=imN, L-Hist, py, nic, and pz) were prepared from trans-[Ru(NH₃)₄L(SO₄)]⁺ by the room temperature reaction of the corresponding

Syntheses and spectroscopic properties

The syntheses of the previously unreported complexes trans-[Ru(NH₃)₄(4-acpy)(NO)]³⁺ (I) and trans-[Ru(NH₃)₄(4-pic)(NO)]³⁺ (II) followed the general procedures described for other trans-[Ru(NH₃)₄L(NO)]³⁺ (L=py, pz, nic, L-Hist, imN) [9], [10]. The physical properties, such as electrochemical and spectral, are similar to those with L=py, pz, nic, L-Hist, imN [8]. Crystallographic structural studies [8] have confirmed the trans configuration for such complexes with the ammines in the equatorial

Summary

The present study has shown that near-UV irradiation of trans-[Ru(NH₃)₄L(NO)]³⁺ solutions at λ_irr, corresponding to a Ru d_π-NO MLCT transition of these complexes, leads to NO photoaquation and formation of the Ru(III) ion trans-[Ru(NH₃)₄L(H₂O)]³⁺. Interestingly, this photochemistry is not observed when the lowest energy MLCT band(s) are excited. The quantum yields for this process is somewhat dependent on the nature of L and on the solution pH. Higher NO photolabilization quantum yields were

Acknowledgements

The authors thank grants and fellowships from Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) (Grant No. 99/07109-9), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), and Fundação Coordenadoria de Aperfeiçoamento do Pessoal de Ensino Superior (CAPES). Rose Maria Carlos acknowledges FAPESP for a post-doctoral fellowship. Alessander A. Ferro acknowledges a Ph.D. fellowship from FAPESP. The authors thank Prof. A.B.P. Lever for providing some supplementary

References (27)

P.C. Ford et al.
Coord. Chem. Rev.
(1998)
J.L. Bourassa et al.
Coord. Chem. Rev.
(2000)
C.F. Works et al.
Inorg. Chem.
(2002)
P.C. Ford et al.
Chem. Rev.
(2002)
F. DeRosa et al.
Abstr. Pap. Am. Chem. Soc.
(2001)
M.A. DeLeo et al.
Coord. Chem. Rev.
(2000)
J.L. Bourassa et al.
Coord. Chem. Rev.
(2000)
R. Bakhtiar et al.
Gen. Pharmacol.
(1999)
T.D. Carter et al.
Br. J. Pharmacol.
(1997)
M.J. Clarke
Coord. Chem. Rev.
(2002)
M.J. Clarke et al.
Struct. Bond.
(1993)
H. Kunkely et al.
Inorg. Chim. Acta
(2002)
K. Szacilowski et al.
J. Photochem. Photobiol. A
(2001)
M.G. DeOliveira et al.
J. Chem. Soc. Dalton
(1995)
V. Togniolo et al.
Inorg. Chim. Acta
(2001)
K. Szacilowski et al.
Coord. Chem. Rev.
(2000)
G. Stochel et al.
Coord. Chem. Rev.
(1998)
J.C. Toledo et al.
J. Inorg. Biochem.
(2002)
J. Bordini et al.
Inorg. Chem.
(2002)
V.R. de Souza et al.
J. Chem. Soc., Dalton Trans.
(2003)
A.K. Patra et al.
Angew. Chem., Int. Ed.
(2002)
A.K. Patra et al.
Inorg. Chem.
(2003)
E. Tfouni et al.
Coord. Chem. Rev.
(2003)
S.D.S. Borges et al.
Inorg. Chem.
(1998)
M.G. Gomes et al.
J. Chem. Soc., Dalton. Trans.
(1998)
B.R. McGarvey et al.
Inorg. Chem.
(2000)
(a)A.I. Vogel, Química Orgânica. Análise Orgânica Qualitativa. 3rd ed., Rio de Janeiro. Livro Técnico S/A vol. 1....D. Perrin et al.
Purification of laboratory chemicals
(1988)
L.G.F. Lopes, D.W. Franco, to be...
G. Malouf et al.
J. Am. Chem. Soc.
(1977)
E. Tfouni et al.
Inorg. Chem.
(1980)
M.L. Bento et al.
Inorg. Chem.
(1988)

H. Taube

Pure Appl. Chem.

(1979)

S. Moncada et al.

Pharmacol. Rev.

(1991)

D.A. Wink et al.

Science

(1991)

S.H. Snyder

Science

(1992)

D.A. Wink et al.

Methods Enzymol.

(1996)

K. Miranda et al.P.C. Ford et al.

FEBS Lett.

(1993)

Cited by (73)

Recent advances on the development of NO-releasing molecules (NORMs) for biomedical applications
2024, European Journal of Medicinal Chemistry
Nitric oxide (NO) is an important biological messenger as well as a signaling molecule that participates in a broad range of physiological events and therapeutic applications in biological systems. However, due to its very short half-life in physiological conditions, its therapeutic applications are restricted. Efforts have been made to develop an enormous number of NO-releasing molecules (NORMs) and motifs for NO delivery to the target tissues. These NORMs involve organic nitrate, nitrite, nitro compounds, transition metal nitrosyls, and several nanomaterials. The controlled release of NO from these NORMs to the specific site requires several external stimuli like light, sound, pH, heat, enzyme, etc. Herein, we have provided a comprehensive review of the biochemistry of nitric oxide, recent advancements in NO-releasing materials with the appropriate stimuli of NO release, and their biomedical applications in cancer and other disease control.
Dark cytotoxicity beyond photo-induced one of silica nanoparticles incorporated with Ru<sup>II</sup> nitrosyl complexes and luminescent {Mo<inf>6</inf>I<inf>8</inf>} cluster units
2024, Journal of Photochemistry and Photobiology A: Chemistry
The present work reports the synthesis of the silica nanoparticles (SNs) incorporated by two photoactive components, which are the representatives of Ru^II nitrosyl complexes and [{Mo₆I₈}(CH₃COO)₆]²⁻ cluster units. The Ru^II nitrosyl complexes are incorporated through the doping procedure into the SNs. The embedding of amino-groups onto the Ru^II-doped SNs facilitates the deposition of the cluster units, thus, resulting in the heterometallic core–shell SNs. Combination of the two photoactive components in the SNs results in the anti-synergistic effect on the photochemical and photodynamic activities of the Ru^II and {Mo₆I₈}-based complexes correspondingly. The enhanced leaching of the cluster units from the heterometallic SNs correlates with the nitrosyl → nitro transformation of the encapsulated Ru^II nitrosyl complexes. The formation of the so-called protein corona onto the heterometallic SNs is revealed as the reason for high colloid stability and efficient cell internalization, which is visualized through the red emission of the {Mo₆I₈}-clusters. The cytotoxicity measurements reveal both synergistic effect of both components on the cytotoxicity evaluated in the so-called dark conditions and anti-synergistic effect on the photo-induced cytotoxicity. The significant dark cytotoxicity of the heterometallic SNs correlates with their high internalization and the enhanced leaching of the cluster units.
Photoactivated metal complexes for drug delivery
2023, Comprehensive Inorganic Chemistry III, Third Edition
Photochemical release (uncaging) of small bioregulatory or therapeutic molecules at physiological sites offers exquisite control of timing, location and dosage. However, photo-uncaging faces two major problems that challenge its therapeutic applications: the relatively poor transmission of visible light through tissue and the need to deliver the appropriate precursors to the desired targets. In this chapter we provide an overview of the metal complexes and delivery platforms designed to provide spatial-temporal control of such delivery.
Ruthenium and Osmium Complexes Containing NHC and π-Acid Ligands
2022, Comprehensive Organometallic Chemistry IV: Volume 1-15
Understanding of [RuL(ONO)]<sup>n+</sup> acting as nitric oxide precursor, a theoretical study of ruthenium complexes of 1,4,8,11-tetraazacyclo- tetradecane having different substituents: How spin multiplicity influences bond angle and bond lengths (Ru-O-NO) in releasing of NO
2021, Journal of Inorganic Biochemistry
Generation of nitric oxide has been a great interest in cell biology as it involves a wide range of physiological functions including the blood pressure control; thus the exploitation of ruthenium chemistry has been motivated in biochemical and clinical points of view. Herein, the structural and electronic properties of ruthenium(II) complexes of 1,4,8,11-tetraazacyclotetradecane containing pyridyl, imidazole and benzimidazole (L¹, L², L³) were analyzed theoretically in the context of how spin multiplicity plays a crucial role influencing the NO release from the LRu-ONO moiety. The results show that β-cleavage of nitrito in the complex motivates the release of NO as it depends highly on total spin multiplicity of metal ion altering significantly the geometrical parameters; particularly, a decrease of bond length of Ru-ONO is highly associated with an increase of RuO-NO bond distance that correlates with the decrease of the Ru-O-NO bond angle ultimately leading to the release of NO; apparently, the bending nature of Ru-O-NO defines its release from the complex. This is consistent with orbital energy (d_x²-_y²) where the stabilization of axial Ru-O bond in the complex was observed, and proved by molecular orbital studies. In the excitation of the complex (singlet to triplet or singlet to quintet), the NO release has been facilitated, agreeing with the Gibbs free energy data where a lower energy for NO release was obtained compared to other types of excitations. In the calculated electronic spectra, a visible broad band with relatively high intensity for [RuL¹ONO]⁺ was observed, agreeing approximately with reported experimental results.
A ruthenium nitrosyl cyclam complex with appended anthracenyl fluorophore
2019, Polyhedron
Citation Excerpt :
The ruthenium tetraamine and tetraazamacrocycle nitrosyl complexes, [Ru(NO)L(N4)]q (N = NH3 or N4 = tetraazamacrocycle), have shown suitable properties for application as NO-carriers [19–21]. These complexes allow the fine tuning of properties of coordinated NO by judicious choice of ligands around the [RuNO] moiety, [7,19,21] resulting in controlled NO release upon chemical reduction or photoactivation [7,22,23]. For instance, the exposure of trans-[Ru(NO)(NH3)4L]3+ (L = P(OEt)3 or pyridine) complexes to a mitochondrial suspension suggested that these compounds are reduced by mitochondrial NADH, releasing NO [24,25].
The complex trans-[Ru(NO)(H₂O)(L)](ClO₄)₃ (L = (1-anthracen-9-ylmethyl)-1,4,8,11-tetraazacyclotetradecane) (RuNOL) was synthesized and characterized, and its photophysics and reactivity were investigated. The FTIR spectrum displays a νNO band at 1840 cm⁻¹, indicating a nitrosonium character. ¹H and ¹³C signals in 1D and 2D NMR spectra were assigned and are consistent with the trans configuration. The UV–Vis spectrum displays maximal absorption bands at 341 nm (log ε 3.74), 363 nm (log ε 3.91), 378 nm (log ε 3.97) and 397 nm (log ε 3.91). Coordination of the [RuNO] moiety to the L ligand strongly quenches the anthracenyl fluorescence, and thus RuNOL exhibits only very weak emission at 390, 418, 440 and 472 nm. Electrochemical studies indicate that cathodic peak potentials at +1.10 V(I_c), −0.1 V(II_c) and −0.4 V(III_c) (vs Ag/AgCl) are related to An⁺/An, {RuNO}^6/7 and {RuNO}^7/8 reduction processes, respectively. The pK_a of coordinated water was estimated as 2.8 ± 0.2 by DPV. The emission of the pendant fluorophore increases upon electrochemical or chemical reduction of RuNOL, and the resulting switch-ON fluorescence is possibly due to NO release from the target complex. Spectroscopic titrations with DNA resulted in hypochromism and red shifts and allowed estimation of binding constants of 1.9 × 10³ (L) and 1.8 × 10³ (RuNOL). Molecular docking showed that RuNOL complex has a great affinity with DNA. The RuNOL complex showed low cytotoxicity toward MCF-7 and NIH-3T3 and was ineffective in healthy HUVEC and A7r5 cell lines in the range of concentration of 1 × 10⁻⁷–1 × 10⁻⁴ mol L⁻¹.

View all citing articles on Scopus

^☆: Taken in part from: Hildo A.S. Silva, Sc.D. Thesis, Instituto de Quı́mica de São Carlos, USP, São Carlos, SP, Brazil, 2001. Simone S.S. Borges, D.Sc. Thesis, Instituto de Quı́mica de São Carlos, USP, São Carlos, SP, Brazil, 1995. Maria G. Gomes, D.Sc. Thesis, Instituto de Química de São Carlos, USP, São Carlos, SP, Brazil, 1995. Alessander A. Ferro, D.Sc. Thesis, Departamento de Quı́mica, FFCLRP-USP, Ribeirão Preto, SP, Brazil, 2000.

¹: Present address: Faculdade de Tecnologia e Ciências de Feira de Santana, Rua Artêmia Pires Freitas, s/n, SIM, 44.115-000, Feira de Santana, BA, Brazil.

View full text

Photochemical reactions of trans-[Ru(NH3)4L(NO)]3+ complexes☆

Abstract

Introduction

Section snippets

Materials and reagents

Syntheses and spectroscopic properties

Summary

Acknowledgements

Coord. Chem. Rev.

Coord. Chem. Rev.

Inorg. Chem.

Chem. Rev.

Abstr. Pap. Am. Chem. Soc.

Coord. Chem. Rev.

Coord. Chem. Rev.

Gen. Pharmacol.

Br. J. Pharmacol.

Coord. Chem. Rev.

Struct. Bond.

Inorg. Chim. Acta

J. Photochem. Photobiol. A

J. Chem. Soc. Dalton

Inorg. Chim. Acta

Coord. Chem. Rev.

Coord. Chem. Rev.

J. Inorg. Biochem.

Inorg. Chem.

J. Chem. Soc., Dalton Trans.

Angew. Chem., Int. Ed.

Inorg. Chem.

Coord. Chem. Rev.

Inorg. Chem.

J. Chem. Soc., Dalton. Trans.

Inorg. Chem.

J. Am. Chem. Soc.

Inorg. Chem.

Inorg. Chem.

Pure Appl. Chem.

Pharmacol. Rev.

Science

Science

Methods Enzymol.

FEBS Lett.

Photochemical reactions of trans-[Ru(NH₃)₄L(NO)]³⁺ complexes☆