One of the challenges of modern inorganic chemistry is translating the potential of metal catalysts to living systems to achieve controlled non-natural transformations. This field poses numerous ...issues associated with the metal compounds biocompatibility, stability, and reactivity in complex aqueous environment. Moreover, it should be noted that although referring to ‘metal catalysis’, turnover has not yet been fully demonstrated in most of the examples within living systems. Nevertheless, transition metal catalysts offer an opportunity of modulating bioprocesses through reactions that are complementary to enzymes. In this context, gold complexes, both coordination and organometallic, have emerged as promising tools for bio-orthogonal transformations, endowed with excellent reactivity and selectivity, compatibility within aqueous reaction medium, fast kinetics of ligand exchange reactions, and mild reaction conditions. Thus, a number of examples of gold-templated reactions in a biologically relevant context will be presented and discussed here in relation to their potential applications in biological and medicinal chemistry.
With the aim of exploiting the use of organometallic species for the efficient modification of proteins through C-atom transfer, the gold-mediated cysteine arylation through a reductive elimination ...process occurring from the reaction of cyclometalated Au
C^N complexes with a zinc finger peptide (Cys
His
type) is here reported. Among the four selected Au
cyclometalated compounds, the Au(C
N)Cl
complex featuring the 2-benzoylpyridine (C
N) scaffold was identified as the most prone to reductive elimination and Cys arylation in buffered aqueous solution (pH 7.4) at 37 °C by high-resolution LC electrospray ionization mass spectrometry. DFT and quantum mechanics/molecular mechanics (QM/MM) studies permitted to propose a mechanism for the title reaction that is in line with the experimental results. Overall, the results provide new insights into the reactivity of cytotoxic organogold compounds with biologically important zinc finger domains and identify initial structure-activity relationships to enable Au
-catalyzed reductive elimination in aqueous media.
With the aim of exploiting the use of organometallic species for the efficient modification of proteins through C-atom transfer, we report here on the gold-mediated cysteine arylation via reductive ...elimination process occurring from the reaction of cyclometalated Au(III) C^N complexes with a zinc finger peptide (Cys2His2 type). Among the four selected Au(III) cyclometallated compounds, the Au(C CO N)Cl2 complex featuring the 2-benzoylpyridine (C CO N) scaffold was identified as the most prone to reductive elimination and Cys arylation in buffered aqueous solution (pH 7.4) at 37°C by high-resolution-LC-electrospray mass spectrometry. DFT and QM/MM studies allowed to propose a mechanism for the title reaction that is in line with the experimental results. Overall, the results provide new insights into the reactivity of cytotoxic organogold compounds with biologically important zinc finger domains and identify initial structure-activity relationships to enable Au(III)-catalysed reductive elimination in aqueous media.
N‐heterocyclic carbenes (NHCs) have become attractive ligands for functionalizing gold nanoparticle surfaces with applications ranging from catalysis to biomedicine. Despite their great potential, ...NHC stabilized gold colloids (NHC@AuNPs) are still scarcely explored and further efforts should be conducted to improve their design and functionalization. Here, the ‘bottom‐up’ synthesis of two water‐soluble gold nanoparticles (AuNP‐1 and AuNP‐2) stabilized by hydrophilic mono‐ and bidentate NHC ligands is reported together with their characterization by various spectroscopic and analytical methods. The NPs showed key differences likely to be due to the selected NHC ligand systems. Transmission electron microscopy (TEM) images showed small quasi‐spherical and faceted NHC@AuNPs of similar particle size (ca. 2.3–2.6 nm) and narrow particle size distribution, but the colloids featured different ratios of Au(I)/Au(0) by X‐ray photoelectron spectroscopy (XPS). Furthermore, the NHC@AuNPs were supported on titania and fully characterized. The new NPs were studied for their catalytic activity towards the reduction of nitrophenol substrates, the reduction of resazurin and for their photothermal efficiency. Initial results on their application in photothermal therapy (PTT) were obtained in human cancer cells in vitro. The aforementioned reactions represent important model reactions towards wastewater remediation, bioorthogonal transformations and cancer treatment.
Small water‐soluble N‐heterocyclic carbene‐stabilized gold nanoparticles (NHC@AuNPs) were synthesized via the bottom‐up approach and showed suitability for applications in catalysis and biomedicine.
•N-heterocyclic carbenes are multifunctional ligands to stabilize gold nanoparticles.•Top-Down and Bottom-Up synthesis of NHC@AuNPs has been achieved.•Size, shape and stability of NHC@AuNPs strongly ...depend on the NHC ligands.•Water soluble gold nanoparticles are useful tools in biomedicine.
The unique properties and high synthetic flexibility of N-heterocyclic carbenes (NHCs) have made them highly attractive tools for the development of new nanomaterials and the fundamental study of their properties. In this review, we focus on the case of NHC-stabilized gold nanoparticles (NHC@AuNPs) with potential for biological applications. AuNPs are ubiquitous in biomedicine, where they serve as versatile scaffolds for drug/gene delivery, biosensing, imaging and therapy. In this context, our review aims at presenting an overview of the relatively few studies reporting on the synthesis and characterization of NHC@AuNPs, with emphasis on the strategies adopted to achieve water-soluble biocompatible nanoparticles. Overall, the possible combinatorial design of NHC ligand shell functionality opens to new perspectives for this relatively unexplored research area.
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Abstract
In recent years, the reactivity of gold complexes was shown to extend well beyond π‐activation and to hold promises to achieve selective cross‐couplings in several C−C and C−E (E=heteroatom) ...bond forming reactions. Here, with the aim of exploiting new organometallic species for cross‐coupling reactions, we report on the Au(III)‐mediated C(sp
2
)−C(sp) occurring upon reaction of the cyclometalated complex Au(C
CH2
N)Cl
2
(
1
, C
CH2
N=2‐benzylpyridine) with AgPhCC. The reaction progress has been monitored by NMR spectroscopy, demonstrating the involvement of a number of key intermediates, whose structures have been unambiguously ascertained through 1D and 2D NMR analyses (
1
H,
13
C,
1
H‐
1
H COSY,
1
H‐
13
C HSQC and
1
H‐
13
C HMBC) as well as by HR‐ESI‐MS and X‐ray diffraction studies. Furthermore, crystallographic studies have serendipitously resulted in the authentication of zwitterionic Au(I) complexes as side‐products arising from cyclization of the coupling product in the coordination sphere of gold. The experimental work has been paralleled and complemented by DFT calculations of the reaction profiles, providing valuable insight into the structure and energetics of the key intermediates and transition states, as well as on the coordination sphere of gold along the whole process. Of note, the broader scope of the cross‐coupling at the Au(III) C
CH2
N centre has also been demonstrated studying the reaction of
1
with C(sp
2
)‐based nucleophiles, namely vinyl and heteroaryl tin and zinc reagents. These reactions stand as rare examples of C(sp
2
)−C(sp
2
) cross‐couplings at Au(III).
In recent years, the reactivity of gold complexes was shown to extend well beyond π‐activation and to hold promises to achieve selective cross‐couplings in several C−C and C−E (E=heteroatom) bond ...forming reactions. Here, with the aim of exploiting new organometallic species for cross‐coupling reactions, we report on the Au(III)‐mediated C(sp2)−C(sp) occurring upon reaction of the cyclometalated complex Au(CCH2N)Cl2 (1, CCH2N=2‐benzylpyridine) with AgPhCC. The reaction progress has been monitored by NMR spectroscopy, demonstrating the involvement of a number of key intermediates, whose structures have been unambiguously ascertained through 1D and 2D NMR analyses (1H, 13C, 1H‐1H COSY, 1H‐13C HSQC and 1H‐13C HMBC) as well as by HR‐ESI‐MS and X‐ray diffraction studies. Furthermore, crystallographic studies have serendipitously resulted in the authentication of zwitterionic Au(I) complexes as side‐products arising from cyclization of the coupling product in the coordination sphere of gold. The experimental work has been paralleled and complemented by DFT calculations of the reaction profiles, providing valuable insight into the structure and energetics of the key intermediates and transition states, as well as on the coordination sphere of gold along the whole process. Of note, the broader scope of the cross‐coupling at the Au(III) CCH2N centre has also been demonstrated studying the reaction of 1 with C(sp2)‐based nucleophiles, namely vinyl and heteroaryl tin and zinc reagents. These reactions stand as rare examples of C(sp2)−C(sp2) cross‐couplings at Au(III).
The mechanism of C(sp2)−C(sp) coupling templated by the Au(III) cyclometalated complex Au(CCH2N)Cl2 has been investigated. By tuning the reaction conditions and monitoring its progress by NMR, a number of intermediate species involved in the reductive elimination process could be isolated and characterised by different spectroscopic and analytical methods, including XRD, as well as by DFT studies.
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