Photo-activated CO-release in the amino tungsten Fischer carbene complex, [(CO)5WC(NC4H8)Me], picosecond time resolved infrared spectroscopy, time-dependent density functional theory, and an antimicrobial study

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Highlights

  • In [(CO)5WC(NC4H8)Me] psTRIR indicates that CO-loss occurs via an excited state, and with a quantum yield of ~70%.

  • Formation of a cis-CO loss product is supported using TDDFT calculations.

  • Antibacterial activity at neutral pH is enhanced by irradiation.

Abstract

Picosecond time-resolved infrared spectroscopy was used to probe the photo-induced early state dynamics preceding CO loss in the Fischer carbene complex, [(CO)5WC(NC4H8)CH3]. Time-dependent density functional theory calculations were employed to help in understanding the photochemical and photophysical processes leading to CO-loss. Electrochemical initiated CO release was quantified using gas chromatography. The potential of [(CO)5WC(NC4H8)CH3], as an antimicrobial agent under irradiation conditions was studied using a Staphylococcus aureus strain.

Introduction

Fischer carbene complexes have been used widely as reagents in various organic transformations, and in organometallic synthesis, using both thermal and photochemical approaches [[1], [2], [3], [4], [5]]. Fischer carbene complexes of group 6 metals have been shown to react under photochemical conditions with imines, alkenes, aldehydes or alcohols producing a wide variety of useful compounds including β-lactams, β-lactones, cyclobutanones, or amino esters [[6], [7], [8], [9]]. Recently low temperature matrix isolation and time resolved spectroscopy has been used in identifying the various intermediates generated in these processes. In 1988, Hegedus and co-workers, proposed that visible light irradiation results in photocarbonylation of alkoxy Fischer carbenes, via either a short lived metallocyclopropanone or a metallaketene intermediate [[10], [11], [12]]. We and others have used picosecond time-resolved infrared spectroscopy to confirm the formation of a metallaketene intermediate species [13,14]. Fischer carbene complexes containing alkoxy groups on the carbene carbon, such as [(CO)5MC(OMe)Me] (M = Cr or W), undergo anti-syn isomerisation of the alkoxy substituent following low energy photolysis. Increasing the excitation energy, however, can result in the formation of a reactive metallaketene intermediate (100 ps) in the case of the chromium analogue. This excited state was detected using picosecond time-resolved infrared spectroscopy (psTRIR) [13], and supported by quantum chemical calculations. For M = Cr, time-dependent density functional theory (TDDFT) calculations indicate that the metallaketene-chromium intermediate has singlet character, while in the case of the tungsten analogue, the metallaketene intermediate is produced from a triplet state [13,15]. In addition, to these two process, the alkoxy based Fischer carbene compounds also undergo photoinduced CO-loss following higher energy photolysis [16,17]. Previously we have shown that replacement of the alkoxy group by an amino substituent (pyrrolidine), greatly enhances the quantum efficiency for CO loss, and the photon energy required to achieve CO-loss is greatly reduced [18]. For example, when [(CO)5CrC(NC4H8)(Me)] was irradiated at λ = 400 nm, rapid (<50 ps) CO loss occurs, with a quantum yield of approximately 70%. No evidence was obtained for the formation of metallaketene intermediates or metallacyclopropanone excited states with this system, which is not surprising as amino Fischer carbene complexes are known to be poor reagents in the synthesis of β-lactams. Among the very few reports on the photochemistry of tungsten based amino Fischer carbene complexes Rooney et al. used Raman spectroscopy, to identify [(CH3CN)(CO)4WC(NC4H8)(SiPh3)] following excitation of [(CO)5WC(NC4H8)(SiPh3)] in acetonitrile [19]. While the synthetic applications of Fischer carbenes are well known, more recently metal carbonyls have been studied for both antimicrobial effects and therapeutic applications [20]. The toxic effects of inhaled environmental CO are well known, but surprisingly the important role of CO as an intracellular messenger, regulating physiological and cryoprotective processes in the body is less understood [21]. The positive effects of CO, which may have clinical applications include vasodilation, anti-inflammatory, anti-proliferative and anti-apoptotic activities [22]. However, for clinical applications, controlling the delivery of CO gas is essential but challenging. Harnessing CO, in CO-releasing compounds (CO-RMs) where a light or electrochemical stimuli can be used to break bonds and liberate “free CO” has been suggested as a means to control delivery for clinical applications [23,24]. Light induced CO release from molecules (photo-CORMS) may facilitate controlled timing, dosage and location of CO release for on-target applications [25,26]. The development of photoCORMs includes compounds absorbing in the ultraviolet, the visible region, and ideally into the therapeutic window [27]. The photochemistry of a wide range of metal carbonyls have been studied in aqueous media, from the original studies which focused on Fe(CO)5 and Mn2(CO)10 [28], to others containing for example tripodal, di-imine or bipyridine type ligands, and including metal centers such as Mo, W, Re or Ru [[29], [30], [31], [32], [33], [34], [35], [36], [37], [38], [39], [40], [41], [42]]. The antimicrobial properties of metal carbonyl compounds against both E. coli and S. aureus were reported by Nobre and co-workers who demonstrated the superior bactericidal activity of CORMs versus using solely carbon monoxide gas [43]. Following these initial antimicrobial studies, many other metal carbonyls compounds based on Mn, Fe and Cu have been assessed for bactericidal properties, both in the presence and absence of a light source [[44], [45], [46], [47],[50], [51], [52], [53], [54]]. Chromium based Fischer carbene complexes have previously been studied as CO-releasing modalities in the absence of light in aqueous media where myogloblin was used to quantify CO. [34] Under the conditions employed, nucleophilic attack by water was reported to be important for CO loss, and a clear correlation between the electrophilicity of the carbene carbon and the rate of CO release in solution was reported. In this study, we report the results from a ps-TRIR investigation on the [(CO)5WC(NC4H8)CH3] compound combined with an electrochemical study where induced CO loss is confirmed using gas chromatography. Similarly, to the chromium analogue, the tungsten amino Fischer carbene complex, undergoes efficient CO-loss using 400 nm excitation, with no evidence for the formation a metallaketene intermediate from the time resolved studies [13,18]. The photochemistry and the high quantum yield for CO-loss is supported using TDDFT calculations. Furthermore, the potential application of the compound as an antimicrobial agent was assessed using a Staphylococcus aureus strain (ATCC 25923).

Section snippets

UV–vis spectroscopy

UV–vis spectra were measured on an Agilent 8453 UV–vis spectrophotometer in a 1 cm quartz cell using spectroscopic grade solvents.

NMR spectroscopy

1H NMR was recorded on a Bruker AC 400 spectrophotometer in CDCl3 and were calibrated according to the deuterated solvent peak.

Picosecond time-resolved infrared spectroscopy

The TRIR experiments were performed at the University of Amsterdam. UV pump and mid-IR probe pulses were generated by a Ti:sapphire laser with a repetition rate of 1 kHz were utilised. The UV pump pulse (400 nm) was generated by second

Results and discussion

The UV–vis spectrum of [(CO)5WC(NC4H8)Me] in n-heptane is presented in Fig. 1. The main features of this spectrum are an absorption maximum at 337 nm and a shoulder at 364 nm. The spectrum is consistent with those of other Fischer carbene complexes reported in the literature [19,67]. Superimposed on the experimental spectrum are the vertical excitation energies to singlet excited states (represented by black lines) calculated by TDDFT methods and the excitation wavelength used in the TRIR

Conclusion

The tungsten based amino carbene complex, [(CO)5WC(NC4H8)Me] was assessed for both photo, and electrochemical CO-release. The CO-loss photoproduct cis-[(CO)4WC(NC4H8)Me] was generated via the formation of an excited state over 80 ps, as evident by picosecond time resolved infrared spectroscopy, and was further supported by quantum chemical calculations. From cyclic voltammetry studies, the complex also releases CO, but this approach is less efficient than when a photo-stimuli is used. The

Declaration of competing interest

There is no conflict of interest concerning the results stated in this manuscript.

The funding sources have been stated in the manuscript.

Acknowledgements

The authors thank the Amsterdam Laboratory under EU access-LLAMS-1961. We would also like to thank the Irish Research Council RS/2012/341 (SM), a SFI-13/TIDA/E2763 grant (YH and MTP), and the Health Research Board-Diabetes Ireland Research Alliance HRBMRCG-2018-01 (AR) for financial support. We would also like to thank the DJEI/DES/SFI/HEA Irish Centre for High-End Computing (ICHEC) for the provision of computational facilities and support.

References (72)

  • M. Landman et al.

    Fac and mer dppe-substituted Fischer carbene complexes of chromium: X-ray, DFT and electrochemical study

    J. Organomet. Chem.

    (2014)
  • P.V. Simpson et al.

    Antibacterial and antiparasitic activity of manganese(I) tricarbonyl complexes with ketoconazole, miconazole, and clotrimazole ligands

    Organometallics

    (2015)
  • K.S. Davidge et al.

    Carbon monoxide-releasing antibacterial molecules target respiration and global transcriptional regulators

    J. Biol. Chem.

    (2009)
  • K.H. Dötz et al.

    Fischer carbene complexes in organic synthesis: metal-assisted and metal-templated reactions

    Chem. Rev.

    (2009)
  • K. Endo

    Development of neighboring electrophilic activation of active center in catalytic reactions via organometallic intermediates

    Bull. Chem. Soc. Jpn.

    (2017)
  • Y.G.N. Iwasawa et al.

    Fischer-type carbene complexes in organic synthesis

    J. Synth. Org. Chem.

    (1998)
  • J. Santamaría et al.

    Beyond Fischer and Schrock carbenes: non-heteroatom-stabilized group 6 metal carbene complexes-a general overview

    Org. Chem. Front.

    (2016)
  • I. Fernández et al.

    Photochemistry of group 6 Fischer carbene complexes: beyond the photocarbonylation reaction

    Acc. Chem. Res.

    (2011)
  • I. Fernández et al.

    The photochemical reactivity of the “photo-inert” tungsten (Fischer) carbene complexes

    Angew. Chemie-Int. Ed.

    (2005)
  • I. Fernández et al.

    The noncarbonylative photochemistry of group 6 Fischer carbene complexes

    Eur. J. Inorg. Chem.

    (2008)
  • Z.F. Zhang et al.

    Mechanistic study for the photochemical reactions of d6 M(CO)5(CS) (M = Cr, Mo, and W) complexes

    ACS Omega

    (2017)
  • L.S. Hegedus

    Transition metals in the synthesis and functionalization of indoles

    Angew. Chemie Int. Ed. English.

    (1988)
  • L.S. Hegedus

    Synthesis of amino acids and peptides using chromium carbene complex photochemistry

    Acc. Chem. Res.

    (1995)
  • S. McMahon et al.

    An investigation into the photochemistry of, and the electrochemically induced CO-loss from, [(CO)5MC(OMe)Me](M = Cr or W) using lowerature matrix isolation, picosecond infrared spectroscopy, cyclic voltammetry, and time-dependent density functional theory

    Dalton Trans.

    (2015)
  • S.C. Nguyen et al.

    Direct observation of metal ketenes formed by photoexcitation of a Fischer carbene using ultrafast infrared spectroscopy

    Organometallics

    (2014)
  • M.L. Gallagher et al.

    Matrix isolation study into the mechanism of photoinduced cyclization reactions of chromium carbenes

    Organometallics

    (1997)
  • A. Hafner et al.

    Chromium-53 nuclear magnetic resonance studies of pentacarbonylchromium-carbene complexes

    J. Am. Chem. Soc.

    (1988)
  • S. McMahon et al.

    Controlled CO release using photochemical, thermal and electrochemical approaches from the amino carbene complex [(CO)5CrC(NC4H8)CH3]

    Phys. Chem. Chem. Phys.

    (2014)
  • A.D. Rooney et al.

    Laser photochemistry and transient Raman spectroscopy of silyl-substituted Fischer-type carbene complexes

    Organometallics

    (1993)
  • H. Yan et al.

    Emerging delivery strategies of carbon monoxide for therapeutic applications: from CO gas to CO releasing nanomaterials

    Small

    (2019)
  • D.G. Levitt et al.

    Carbon monoxide: a critical quantitative analysis and review of the extent and limitations of its second messenger function

    Clin. Pharmacol. Adv. Appl.

    (2015)
  • H.H. Kim et al.

    Therapeutic aspects of carbon monoxide in cardiovascular disease

    Int. J. Mol. Sci.

    (2018)
  • L. Flanagan et al.

    The antimicrobial activity of a carbon monoxide releasing molecule (EBOR-CORM-1) is shaped by intraspecific variation within Pseudomonas aeruginosa populations

    Front. Microbiol.

    (2018)
  • M. Faizan et al.

    CO-releasing materials: an emphasis on therapeutic implications, as release and subsequent cytotoxicity are the part of therapy

    Materials (Basel)

    (2019)
  • A.E. Pierri et al.

    A photoCORM nanocarrier for CO release using NIR light

    Chem. Commun.

    (2015)
  • Z. Li et al.

    Dinuclear PhotoCORMs: dioxygen-assisted carbon monoxide uncaging from long-wavelength-absorbing metal-metal-bonded carbonyl complexes

    Inorg. Chem.

    (2017)
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