Cyclic voltammetry, relativistic DFT calculations and biological test of cytotoxicity in walled-cell models of two classical rhenium (I) tricarbonyl complexes with 5-amine-1,10-phenanthroline

doi:10.1016/j.cplett.2018.11.043

Chemical Physics Letters

Volume 715, January 2019, Pages 231-238

Dedicated to Dr. Ivonne Chávez M. (PUC) on her retirement.

https://doi.org/10.1016/j.cplett.2018.11.043 Get rights and content

Highlights

•
Two classical Re(I) tricarbonyl complexes (D1 and D2) were obtained at high yield and the fac form.
•
Relativistic DFT, TD-DFT, and SOC-TDDFT were performed to determine the nature of emission.
•
Lability of halogens in D1 and D2 was determined by Morokuma–Ziegler analysis.
•
D1 and D2 were studied regarding their cytotoxicity in walled-cells.

Abstract

fac-[Re(CO)₃(5-amine-1,10-phenanthroline)Cl or Br] (D1 and D2) were synthesized and characterized. D2 was obtained by al alternative method. The electrochemical reaction mechanisms of both D1 and D2 corresponded to EEC for reduction, and ECE for oxidation. Moreover, geometry, electronic, and luminescent properties were analyzed by relativistic DFT and TD-DFT calculations. We determined the lability of single bond Cl and Br by a Morokuma–Ziegler analysis. We found that these compounds were less toxic than the ligand alone, and it depends on the cell model tested, where bacteria seem to be more susceptible than yeasts.

Graphical abstract

Classical Re(CO)₃⁺ complexes were studied by cyclic voltammetry, relativistic computational approximations and cytotoxicity essays in walled cell.

Introduction

Fluorescence microscopy has been considered one of the biggest step in the study of both cell morphology and physiology [1]; albeit it presents new challenges, especially regarding development of improved fluorescent biomarkers [2]. d⁶ metals complexes, such as rhenium (I) tricarbonyl, have been extensively studied due to their properties as biomarkers, such as long excited-state lifetimes and large Stokes shifts, which make them efficient agents for fluorescence microscopy [3]. On the other hand, rhenium (I) tricarbonyl complexes can be modified by the addition of different ligands, including dinitrogenated ligands (N,N), such as 2,2′-bipyridine or 1,10-phenanthroline [4]. Although some authors postulated that rhenium (I) tricarbonyl complexes are not suitable to stain yeasts (fungi), presumably because of the presence of the cell wall [4], we have demonstrated that it is possible to fluorescently stain walled cells (including yeasts and bacteria) with classical rhenium (I) tricarbonyl complexes that harbor suitable ancillary ligands [5]. Interestingly, dinitrogenated ligands (N, N), such as 2,2′-bipyridine, 1,1-phenanthroline or derivatives, can be cytotoxic by itself [6], or in transition metal complexes [7], against different cell models, including prokaryotic and eukaryotic cells.

In the present work, we synthesized two complexes: fac-[Re(CO)₃(phenNH)Cl] (D1) and fac-[Re(CO)₃(phenNH)Br] (D2), where phenNH is 5-amine-1,10-phenanthroline (Scheme 1). Although these rhenium (I) complexes can be considered as classical compounds because they have been already reported, they have been characterized only regarding catalysis, CO₂ reduction, and as sensors [8]. Although D1 has been synthesized using a known protocol based on Re(CO)₅Cl [9], D2 was synthesized by a novel method developed in our laboratory, with high yields and purity in short time. We also present a full characterization of both D1 and D2, including cyclic voltammetry. In addition, we performed relativistic theoretical calculations to better understand electronic transitions, as well as NBO analyses. We also assessed cytotoxicity of D1, D2, and even of phenNH ligand alone in four different walled-cell models, including yeasts and bacteria. We found that phenNH alone was cytotoxic against all the cell models tested. On the other hand, the effect observed for both D1 and D2 were undistinguishable from the vehicle alone (i.e. DMSO) in the two yeasts tested, indicating that, in this case, the cytotoxicity of phenNH is clearly reversed in the metal complexes. By contrast, although cytotoxicity of the complexes was partially attenuated in bacteria, we observed a statistically significant difference between D1 and D2, with an increased cytotoxicity for D1. These results indicate that, at least in the prokaryotic models used, small changes in the ancillary ligands can also modulate cytotoxicity in this kind of compounds.

According to our results, D1 and D2 could be useful as biomarker precursors for fungal cells due to their low cytotoxicity in this cell models. Considering that other similar compounds harboring a Schiff base as ancillary ligand (i.e. [fac-Re(CO)₃(bpy)L]⁺, where bpy is a 2,2′-bipyridine or a derivative, and L is an E-2-((3-amino-pyridin-4-ylimino)-methyl)-4,6-di-tert-butylphenol) are useful to stain yeasts [10], we postulate that both D1 and D2, with suitable ancillary ligands, could be used as precursors for biomarkers in the future.

Section snippets

Experimental and computational methods

All starting materials were purchased from Merck and Aldrich and used with no further purification. Acetonitrile (CH₃CN) was drying molecular sieves and purged under argon gas for electrochemical applications [11]. Synthesis and characterization of rhenium (I) tricarbonyl complexes is described in the ESI^†.

Synthesis and characterization

The D1 complex was synthesized by a traditional route [8], [17], [18]. In the case of D2, this compound was prepared by direct reacting bromotricarbonyl(tetrahydrofuran)rhenium (I) dimer and phenNH (1:2) in toluene. This method requires no reflux or inert atmosphere (see Scheme S1 in the ESI^†) [10]. An orange-yellow solid of D1 was recrystallized from ethanol/diethyl ether (2:1) with an 85% yield. An orange-brown solid of D2 was recrystallized from toluene/diethyl ether (2:1) with more than 87%

Conclusions

In this work, we synthesized two classical neutral rhenium (I) tricarbonyl complexes, D1 and D2. In both cases, we determined that the fac isomers are strongly favored, indicating that this kind of compounds can be obtained by synthesis different methods. Regarding the emission, both D1 and D2 present a LMCT involving a π orbital (LUMS a_1/2^*) located on the phenNH moiety and HOMS (a_1/2) orbital of Re atom. Thus, the emission is a mixture of the triplet (96%) and the singlet state (4%).

Acknowledgements

We thank FONDECYT 11170637; J.A.F. thanks FONDECYT 1181638 and Proyecto Núcleo UNAB DI-1419-16/N. We thank Dr. María Angelica del Valle (Laboratorio de Electropolímeros, PUC Chile); and B.A. Alfonso Inzunza G. for his help with the English translation.

References (48)

M. Kaplanis et al.
J. Inorg. Biochem.
(2014)
Y. Jiang et al.
Inorg. Chim. Acta
(2016)
A. Świtlicka-Olszewska et al.
J. Lumin.
(2016)
C. Kefalidi et al.
Polyhedron
(2016)
M.A. del Valle et al.
Electrochem. Commun.
(2009)
C. Ramírez et al.
Electrochim. Acta
(2016)
A. Munoz-Castro et al.
Chem. Phys. Lett.
(2017)
M. Cuenca-Estrella et al.
Clin. Microbiol. Infect.
(2003)
D.A. Kurtz et al.
Inorg. Chim. Acta
(2015)
R. Kia et al.
Inorg. Chim. Acta
(2016)

M.V. Sigalov et al.

Eur. J. Org. Chem.

(2017)

B.J. Neyhouse et al.

Inorg. Chim. Acta

(2018)

R. Czerwieniec et al.

Inorg. Chim. Acta

(2005)

V.V. Pavlishchuk et al.

Inorg. Chim. Acta

(2000)

A. Carreno et al.

Chem. Phys. Lett.

(2017)

P.P. Mokolokolo et al.

Inorg. Chim. Acta

(2018)

P. Cantero-Lopez et al.

Chem. Phys. Lett.

(2017)

H. Yoshimura

Biochemistry

(2018)

M. Hauser et al.

Chem. Rev.

(2017)

V. Fernandez-Moreira et al.

Chem. Commun. (Camb.)

(2010)

A.J. Amoroso et al.

Chem. Commun. (Camb.)

(2007)

A. Carreño et al.

New J. Chem.

(2017)

A. Carreno et al.

New J. Chem.

(2016)

M.A. Pardo et al.

J. Chil. Chem. Soc.

(2014)

Cited by (21)

Synthesis and characterization of quinoxaline-based rhenium(I) organometallic compounds: Biological and computational applications
2024, Journal of Molecular Structure
Rhenium(I) organometallic compounds (C¹-C⁶) with substituted quinoxaline Schiff base-based ligands (L¹-L⁶) were synthesized and characterized using spectroscopic techniques such as ¹HNMR , LC-MS, FT-IR spectroscopy, conductivity measurement, and elemental analysis. CT-DNA was tested under the impact of complexes using absorbance titration and viscosity measuring techniques to evaluate the binding capacities and manner. The compounds bind to the DNA by partial intercalation. The K_b values for all synthesized compounds are in the range of 0.44 to 1.72×10⁵ M⁻¹ in the absorption titration experiment. The evaluation of compounds binding to BSA was carried out using a fluorescence quenching study and the K_sv values were observed in the range of 0.93 to 1.67×10⁴ M⁻¹. The K_sv values for the fluorescence quenching-based DNA binding investigation were observed in the range of 0.75 to 1.87×10⁴ M⁻¹. The findings of the molecular docking investigations support the previously described point to an intercalation type of binding. The protein binding studies of all the synthesized compounds were examined using an absorption titration experiment, and the K_b values for all of the compounds range from 0.64 to 1.35×10⁴ M⁻¹. The structures of Re(I) complexes were optimized using DFT investigations. The antibacterial activity of organometallic compounds was tested against two Gram-positive and three Gram-negative pathogens, and the results showed that organometallic compounds outperform all ligands in this regard. The pharmacokinetic profile of each synthesized molecule was assessed as part of the ADME investigation using the online tools SwissADME and admetSAR. The MCF-7 cancer cell line was used to examine the anticancer effects of the compounds.
Effect of an amine functionalization of phenanthroline ligand associated with an ester-pyridine ligand on excited-state properties of Re(I) complex. Interplay between two 3MLCT
2023, Inorganica Chimica Acta
In this work, the synthesis, characterization and photophysical properties of rhenium(I) polypyridyl compound, fac-[Re(et-isonic)(NH₂phen)(CO)₃]PF₆, where NH₂phen = 5-amino-1,10-phenanthroline and et-isonic = ethyl isonicotinate, are reported. The compound exhibited a broad absorption band around 300–500 nm that by Time-Dependent Density Functional Theory (TD-DFT) corresponds to a mixture of IL_NH2phen and MLCT_Re→NH2phen transitions and a contribution of the charge transfer transition MLCT_{Re→et-isonic}. Contrary to what is expected, the change of Cl (λ_max = 490 and 565 nm; ϕ = 0.002; τ = 0.49 ± 0.07 μs and < 0.020 μs) for et-isonic ligand (λ_max = 590 nm; ϕ = 0.003; τ = 0.43 ± 0.03 μs and 0.044 ± 0.014 μs), a π-acceptor ligand, promoted a bathochromic shift of the emission maxima in acetonitrile solution. This distinct behavior can be rationalized in terms of the inversion of the lowest-lying excited state of the usual observed MLCT_Re→NN to the unusual MLCT_{Re→et-isonic}. On the other hand, the contribution of ligand-based excited state in the deactivation process cannot be ruled out. Additionally, as a triplet emitter, a high quantum yield for the singlet oxygen generation (0.50 ± 0.03) can be associated with either, ³MLCT or a ³LC state. The photophysics ally to the higher singlet oxygen generation reported herein provides new fundamental insights into the understanding of substituent groups on the polypyridyl ligands that are relevant to the practical development of the scientific field.
Effect of carbazole and pyrrolidine functionalization of phenanthroline ligand on ground- and excited-state properties of rhenium(I) complexes. Interplay between 3MLCT and 3IL/3ILCT
2022, Dyes and Pigments
New rhenium(I) tricarbonyl complexes based on the phenanthroline ligand were designed and synthesized to investigate the role of carbazole (cbz) and pyrrolidine (pyrr) substituents in determining thermal, electrochemical and optoelectronic properties. Both pyrr and cbz are electron-releasing substituents, but they differ in the steric hindrance and electron delocalization ability. The impact of pyrr and cbz on ground- and excited-state properties of [ReCl(CO)₃(cbz₂-CH₃phen)] (1) and [ReCl(CO)₃(pyrr₂-CH₃phen)] (2) were investigated with a range of techniques including cyclic voltammetry, absorbance and emission spectroscopies, transient absorption spectroscopy, and they were discussed in comparison with the model chromophore [ReCl(CO)₃(CH₃phen)] (3). Experimental results were supported by theoretical calculations. The most striking difference between the pyrr and cbz groups was seen in their impact on the LUMO energy level. While the attached carbazole groups decreased the LUMO energy of 1, the pyrrolidine ones in 2 resulted in the rise of LUMO energy level compared to the model chromophore. For both 1 and 2, the HOMO got energetically destabilized in agreement with electro-donor abilities of pyrr and cbz substituents. Structural modification of phen backbone resulted also in changes of distribution of occupied MOs of 1 and 2 in relation to 3. Experimentally, it was manifested in noticeable changes of electrochemical and photophysical behaviour of the resulting Re(I) complexes in relation to the model chromophore.
Protein binding and cytotoxicity activities of glutamine based metal complexes
2021, Journal of Molecular Structure
Citation Excerpt :
In the present antioxidant efficacy study, [Cu(II)-(thial-L-gln)2] and [Zn(II)-(thial-L-gln)2] showed the highest free radical scavenging property leads to potent antioxidant activity, can be propagated as a possible therapeutic for cancer and other diseases. Cytotoxic effect of [Cu(II)-(thial-L-gln)2] complex has been studied by MTT assay on PA1(Ovarian cancer) and L929 (fibroblast) cell lines [44]. These two cell lines have been treated with increasing concentrations (6.5˗100 µg/mL) for 24 h, as shown in the supporting information (Table 3).
In the present study, novel metal(II) complexes with an amino acid based bidentate imine ligand (thial-L-gln) derived from thiophene-2-carboxaldehyde (thial) and L-glutamine (L-gln) have been designed theoretically using DFT calculations and successfully synthesized experimentally. Based on the combined (theoretical and experimental) results, tetrahedral/square-planar geometries have been proposed for the complexes. Molecular docking studies indicate greater interactions of [Cu(II)-(thial-L-gln)₂] and [Zn(II)-(thial-L-gln)₂] with the EGFR evidenced by best binding energy and hydrogen-bonded residues during interactions. The antimicrobial and antioxidant studies revealed that all complexes exhibit significant activities as compared to thial-L-gln. From cell viability assay and morphological studies, it has been confirmed that the [Cu(II)-(thial-L-gln)₂] has significant anticancer activity.
Exploring rhenium (I) complexes as potential fluorophores for walled-cells (yeasts and bacteria): Photophysics, biocompatibility, and confocal microscopy
2021, Dyes and Pigments
Citation Excerpt :
However, the bidentate ligand can also modulate the properties of Re (I) tricarbonyl complexes regarding their use as fluorescent probes, contributing both the photophysical and biocompatibility properties [1]. It has been proposed that bidentate (N,N) ligands must harbor relatively small substituents, in order to avoid cell disruption and undesirable lysis [1,5,10]. At present, some Re (I) tricarbonyl complexes harboring 2,2′-bipyridine, and derivatives, have been already tested as fluorescent markers for walled cells [1,2,10,11].
In the present work, we synthesized and characterized two complexes: fac-Re(CO)₃(4,5-diazafluoren-9-one)Br (ReL1) and fac-Re(CO)₃(5,6-epoxy-5,6-dihydro-1,10-phenanthroline)Br (ReL2), where ReL2 has not been reported at present. In this study, we show a complete structural characterization of both ReL1 and ReL2 by elemental analysis, FTIR, ¹H and ¹³C NMR, DEPT, and HHCOSY. Moreover, we carried out UV–Vis and luminescence experiments in organic solvents showing different polarities. In addition, we performed relativistic theoretical calculations to better understand electronic transitions and optical properties. We also assessed the cytotoxicity of ReL1, ReL2, and their respective N,N ligands (i.e., 4,5-diazafluoren-9-one and 5,6-epoxy-5,6-dihydro-1,10-phenanthroline) against walled-cells, including Gram-negative bacteria (Salmonella enterica serovar Typhimurium), non-sporulated Gram-positive bacteria (Staphylococcus aureus), sporulated Gram-positive bacteria (Bacillus cereus), and yeasts (Candida albicans and Cryptococcus spp.). We observed that these complexes exhibited very low or no cytotoxicity. We also found that only ReL2, and not ReL1, exhibited good properties as a luminescent probe for this kind of cells. Accordingly, we found that ReL2 showed good potential to be directly used as a luminescent probe for walled cells, including yeasts (e.g., Candida albicans) and bacteria (e.g., Salmonella enterica), which can be observed by confocal microscopy.
An amine linker group modulates luminescent properties in a Rhenium(I) tricarbonyl complex. How can it be applied for ratiometric oxygen sensing?
2020, Dyes and Pigments
Citation Excerpt :
Considering the energy of each transition, the values of their experimental molar absorptivities (Table 3) and the DFT/TD-DFT results, we assigned the bands centered at 300 and 370 to have major ligand centered character, π→π* and n/π→π* (ILCT), while the low energy band would mainly have MLCT character. This assignation is also compatible with other theoretical calculations reported in the literature [48]. Comparison with the parent compound ReNNBr [20], demonstrated the effect of the presence of the NH2 group, which can be related with the red-shift of the MLCT band.
The UV–Vis absorption spectrum of the rhenium(I) tricarbonyl complex [(NH₂-phen)Re(CO)₃Br] (ReNN-NH₂Br, a deep-orange solid) in solution shows three bands located at 300, 370 and 445 nm. TD-DFT calculations and spectroscopic data indicate that the higher energy band corresponds to a ligand centered transition (LC), while the two lower energy bands have been ascribed to have major ILCT and MLCT character. Excitation at 370 nm leads to two emission bands centered at around 490 nm and 590 nm, which have different nature, ¹ILCT and ³MLCT, respectively. Both show a low luminescent quantum yield, especially the lowest energy band. The emission quantum yields in argon-saturated solutions are largely increased, specially for the band at 590 nm. Our results demonstrate that adding the amino group has a non-innocent effect over the luminescent properties of the complex when is compared with those of [(phen)Re(CO)₃Br] (ReNNBr). The capacity of these complexes to act as singlet oxygen sensitizers and their application as oxygen sensors were explored. Both complexes, ReNNBr and ReNN-NH₂Br, were incorporated in silsesquioxane matrices and tested as ratiometric oxygen sensors using the intrinsic emission of the matrix as an emission internal reference signal. The SSO1-ReNN-NH₂Br films was the most sensitive material for this application.

View all citing articles on Scopus

¹: www.cans.cl.

View full text

Research paperCyclic voltammetry, relativistic DFT calculations and biological test of cytotoxicity in walled-cell models of two classical rhenium (I) tricarbonyl complexes with 5-amine-1,10-phenanthroline

Highlights

Abstract

Graphical abstract

Introduction

Section snippets

Experimental and computational methods

Synthesis and characterization

Conclusions

Acknowledgements

J. Inorg. Biochem.

Inorg. Chim. Acta

J. Lumin.

Polyhedron

Electrochem. Commun.

Electrochim. Acta

Chem. Phys. Lett.

Clin. Microbiol. Infect.

Inorg. Chim. Acta

Inorg. Chim. Acta

Eur. J. Org. Chem.

Inorg. Chim. Acta

Inorg. Chim. Acta

Inorg. Chim. Acta

Chem. Phys. Lett.

Inorg. Chim. Acta

Chem. Phys. Lett.

Biochemistry

Chem. Rev.

Chem. Commun. (Camb.)

Chem. Commun. (Camb.)

New J. Chem.

New J. Chem.

J. Chil. Chem. Soc.

Research paper
Cyclic voltammetry, relativistic DFT calculations and biological test of cytotoxicity in walled-cell models of two classical rhenium (I) tricarbonyl complexes with 5-amine-1,10-phenanthroline