Organometallics – Chemical Communications Blog

Archive for the ‘Organometallics’ Category

Studying Anticancer Agents with XFM

23 Jun 2020

It turns out that rhenium-based compounds have been showing some promising anticancer activity as they’re stable, allow for real time imaging, structurally diverse, and have low off-site toxicity. The most commonly studied complexes are based around a Re(I) tricarbonyl core with the other three binding sites occupied by ligands of varying complexity. Researchers in the US and Australia developed a tricarbonyl Re isonitrile polypyridyl complex fac-[Re(CO)3(dmphen)(para-tolyl-isonitrile)]+, where dmphen = 2,9-dimethyl-1,10-phenanthro-line, called TRIP for short. TRIP showed promising cytotoxicity and can be imaged using confocal fluorescence microscopy, taking advantage of the emissive metal to ligand charge transfer (MLCT) state. The persistence of the emission indicates that the ligands remain bound to the Re even within cells. The complex’s cytotoxicity stems from its inducement of cells to accumulate misfolded proteins, resulting in apoptosis from the unfolded protein response (UPR). UPR induced cell death is relatively uncommon and led the researchers to find a method to characterize the speciation of TRIP in vitro. They used synchrotron X-ray fluorescence microscopy (XFM) to probe the cellular uptake and distribution of TRIP and an iodo-derivative I-TRIP by looking at elemental signals.

Figure 1. Chemical structures of TRIP and I-TRIP

I-TRIP is particularly well-suited to this type of study, as the iodine provides an additional spectroscopic handle on the isonitrile ligand absent in TRIP. Of course, the researchers had to confirm that I-TRIP possessed similar cytotoxicity and working mechanism to TRIP. Various assays and biological studies showed evidence of comparable cytotoxicity and mechanism, demonstrating that altering the substitution of the isonitrile ligand doesn’t significantly impact the bioactivity of the complex. With that settled, the experiments could move to the synchrotron to probe elemental distributions.

Figure 2. XFM elemental distribution maps of HeLa cervical cancer cells treated with either DMSO (control), TRIP, or I-TRIP.

Cells treated with both TRIP and I-TRIP show a clear Re signal, confirming that they can enter and persist in cells. Critically, the colocalization of the Re and I maps for I-TRIP samples indicate that the isonitrile ligand remains bound as a part of the Re complex inside the cells. This strongly suggests that the Re complex is intact while it induces cell death, adding to the developing mechanistic understanding of their activity. This work shows the utility of XRM as a technique to study the distribution of organometallic complexes in living cells. Additionally, the tunability and stable bioactivity of the Re complexes shows that they’re amenable to study by a wide range of techniques that will allow for further mechanistic probing.

To find out more, please read:

X-Ray fluorescence microscopy reveals that rhenium(I) tricarbonyl isonitrile complexes remain intact in vitro

Chilaluck C. Konkankit, James Lovett, Hugh H. Harris and Justin J. Wilson

Chem. Commun., 2020, 56, 6515-6518

About the blogger:

Dr. Beth Mundy is a recent PhD in chemistry from the Cossairt lab at the University of Washington in Seattle, Washington. Her research focused on developing new and better ways to synthesize nanomaterials for energy applications. She is often spotted knitting in seminars or with her nose in a good book. You can find her on Twitter at @BethMundySci.

Comments Off on Studying Anticancer Agents with XFM

Copper A3 Coupling using a Switchable Homogeneous/Heterogeneous Catalyst

06 Nov 2018

A MOC, I learned this week, is a metal-organic cage. I was familiar with MOMs, MOFs and MOBs, but MOCs were a new one. A MOM (metal-organic material) is a coordination-driven assembly constructed from metal nodes linked by organic ligands. MOMs encompass both MOFs (metal-organic frameworks) and MOCs (metal-organic cages). A MOF is an extended network with the potential for inner porosity, and a MOC is a discrete metal-ligand cluster. And that’s just about as far down the nomenclature rabbit hole I’m willing to go. If you’re keeping up you’ll realise that I forgot one! A MOB is a crowd of graduate students competing for free coffee at the public seminar.

Dong and co-workers at Shandong Normal University designed and prepared a MOM catalyst constructed from copper(II) nodes and a tripodal ligand consisting of a phenylic wheel functionalised with diketones. In chloroform these two components arrange into discrete MOC assemblies containing two tripodal ligands and three copper ions. The copper ions in the cluster are each coordinated to two diketone moieties (in a acetylacetonate-like fashion) in a quasi-square planar arrangement.

Synthesis of the tripodal ligand functionalised with diketone coordinating moieties.

An interesting property of the material is that it can switch between the MOC form, soluble in halogenated solvents, and an insoluble MOF that assembles upon addition of 1,4-dioxane. 1,4-Dioxane is both an anti-solvent and a ligand; coordination between copper and 1,4-dioxane binds the discrete MOC cages to each other, arranging them into the extended MOF structure. This behaviour can be exploited to prepare a practical catalyst that combines the benefits of both homogeneous and heterogeneous catalysis, namely that homogeneous catalysts are generally more efficient, selective and easier to study, but heterogeneous catalysis are easier to recover and recycle. What better way to solve this problem than with a catalyst that is homogeneous during the reaction conditions, but heterogeneous when it comes to product separation?

Reversible metal-organic cage MOC(top left)-MOF(top right) metal-organic framework transition mediated by the addition of 1,4-dioxane. Coordination bonds between 1,4-dioxane shown (bottom image).

Reversible MOC(top left)-MOF(top right) transition mediated by the addition of 1,4-dioxane. Coordination bonds between 1,4-dioxane shown (bottom image).

The authors used the A³ coupling reaction to demonstrate this concept in a catalytic reaction. The A³ reaction is a transition metal-catalysed, multi-component coupling reaction between aldehydes, alkynes and amines. The products are propargylamines, practical synthetic intermediates for the synthesis of nitrogen heterocycles. The A³ reaction has been extensively studied and can be effected by a wide range of transition metal catalysts. Its versatility makes it a popular choice as a model catalytic reaction to demonstrate innovative ideas in catalytic design – as the authors have done here.

Coordination-driven assemblies have a unique potential for the synthesis of differentially soluble materials, used by the authors for novel catalytic design. Whether this particular metal-ligand combination can be applied to other copper catalysed reactions remains to be seen, nevertheless the principle offers an innovative approach that augments the range of methods striving to bridge the gap between homogeneous and heterogeneous catalysis.

To find out more please read:

Cu₃L₂ metal-organic cages for A³-coupling reactions: reversible coordination interaction triggered homogeneous catalysis and heterogeneous recovery

Gong-Jun Chen, Chao-Qun Chen, Xue-Tian Li, Hui-Chao Ma and Yu-Bin Dong.
Chem. Commun., 2018, 54, 11550-11553
DOI: 10.1039/c8cc07208f

About the author

Zoë Hearne is a PhD candidate in chemistry at McGill University in Montréal, Canada, under the supervision of Professor Chao-Jun Li. She hails from Canberra, Australia, where she completed her undergraduate degree. Her current research focuses on transition metal catalysis to effect novel transformations, and out of the lab she is an enthusiastic chemistry tutor and science communicator.

Comments Off on Copper A3 Coupling using a Switchable Homogeneous/Heterogeneous Catalyst

Come for the colour changing crystals, stay for the science

31 May 2018

Synthesis of copper bimetallic complexes from imidazolyl ligands, and the solvatochromic materials formed upon crystallization and solvent guest-exchange. The solvatochromic behaviour was quantified with visible-region diffuse reflectance spectra.

During the first inorganic chemistry course I took during my undergraduate degree, our professor started the class by passing around some mineral samples, promising us that if we pursued the chemistry of metals we could work with beautifully coloured crystals every day. At the time, colour seemed like such a trite detail amongst the complexity of the subject. Why would you choose a field of study based on something so simple? Well, after a PhD dominated by pale yellow oils, I think I get it now.

Nikolayenko and Barbour at the University of Stellenbosch in South Africa bring us colour! The authors synthesised organometallic copper complexes, which crystallise to form porous single crystals that drastically change colour upon absorption of various solvents. The authors investigated the solvatochromic mechanism using X-ray crystallography, EPR, UV-visible spectroscopy and DFT calculations. Solvatochromic materials are not just made to look pretty; they have potential to be used as sensitive, selective and recyclable sensors to detect solvent vapours with useful applications in industrial process risk management, chemical threat detection and environmental monitoring.

The researchers synthesised a series of complexes comprised of a bidentate ligand with 2-methylimidazolyl groups coordinated to copper(II) ions. The complexes stack to form channels in the crystal, capable of trapping solvent molecules to give different coloured crystals: DMSO and THF-containing crystals are green (λ_max = 574 nm and 540 nm, respectively), those containing acetonitrile are red (λ_max = 624 nm), and crystals trapping acetone, ether and pentane are yellow (λ_max = 588), orange (λ_max = 598 nm) and red/brown (λ_max = 592 nm), respectively.

The authors revealed a correlation between the size of the solvent guest, coordination geometry of the copper complex, and the ligand field splitting. Small guests such as acetonitrile minimally perturb the metallocyclic framework, preserving a rhombic ligand field geometry (large δ_xy of g values in the EPR spectrum), small ligand d-orbital splitting and red-shifted optical spectra. Large guests such as THF have the opposite effect, giving ligand field geometries approaching tetragonal (small δ_xy), large ligand field d-orbital splitting and blue-shifted optical spectra.

By delving into the complexity beneath a seemingly simple phenomenon, Nikolayenko, Barbour and their co-workers have shown using a series of single-crystal complexes that there is nothing simple about colour (and nothing trite about detail).

To find out more please read:

Supramolecular solvatochromism: mechanistic insight from crystallography, spectroscopy, and theory

Varvara I. Nikolayenko, Lisa M. van Wyk, Orde Q. Munro, Leonard J. Barbour.
Chem. Commun., 2018, Advance Article
DOI: 10.1039/c8cc02197j

About the author

Comments Off on Come for the colour changing crystals, stay for the science

An Organometallic Toolbox for the Study and Synthesis of Unique N-Heterocyclic Carbenes

05 Mar 2018

N-heterocyclic carbenes (NHCs) are an interesting example of chemical curiosity turned commonplace. NHCs are stable singlet carbenes located within an N-heterocycle, in which the carbon centre bears an sp² hybridised pair of electrons. As early as 1835 chemists were thinking about carbenes, with Dumas’ optimistic (if unsuccessful) attempt to synthesise the methylene carbene by dehydrating methanol. For many years the intentional study of carbenes was considered too demanding because of their instability, and so they remained in relative obscurity. A number of seminal papers changed this preconception; in particular, a report by Wanzlick in 1968 reporting the synthesis of the first NHC-metal complex using mercury and the first synthesis of a stable and isolable NHC by Arduengo in 1991.

Intensification in research and interest in NHCs over the past thirty years may have originated with these seminal reports, but it continues because of the success of NHCs in catalysis: both as strongly σ-donating metal ligands and nucleophilic organocatalysts. One of the most valuable features of NHCs is the ability to tailor their steric and electronic properties by altering the heterocyclic ring and N-bound substituents. Accordingly, the study of NHC reactivity and the development of methods to functionalise NHCs are essential for continued innovation in this field.

Drs Marina Uzelac and Eva Hevia at the University of Strathclyde, Scotland, have written a review article summarising organometallic methods to metallate N-heterocyclic carbenes. The work summarises metallation of all three components of the NHC: the carbenic carbon, the heterocyclic backbone and the N-bound substituents.

The lithiated complex (1), synthesised by treatment of the N-heterocyclic carbene NHC with nBuLi, can be transmetallated at the C4 position by a number of main group elements to give a variety of bimetallic complexes (2). These complexes can be selectively quenched to generate NHC complexes with unconventional regiochemistry (3).

The lithiated complex (1) can be transmetallated at the C4 position by a number of main group elements to give a variety of bimetallic complexes (2). These complexes can be selectively quenched to generate NHC complexes with unconventional regiochemistry (3).

To exemplify the breadth of research discussed; beginning with 2,6-diisopropylphenyl (dipp) substituted imidazole-2-ylidenes, the reactivity of the NHC can be unlocked by initial addition of an alkali metal such as lithium, sodium or potassium (see figure). Metallation at the C4 position occurs by deprotonation of the vinyl protons in the NHC backbone, while a second metal coordinates to the carbene electron pair at the C2 position. From this species (1) it is possible to transmetallate the C4 position with a less-polar metal such as zinc, aluminium, gallium, boron or iron to furnish a bi-metallic NHC (2). Interestingly, addition of an electrophilic methyl or proton source to this species exclusively quenches the C2 position, generating a suite of unconventional complexes (3) with the carbene electron pair positioned on the C4 carbon.

Lithiation of NHC complexes: a) deprotonation of the backbone of NHC-borane complex; b) co-complexation of NHC-zinc complex with alkyllithium affording lithium zincate; c) deprotonation of the abnormal carbene complex.

Reactivity of main-group NHC complexes towards lithiation.

Further studies investigate how different reagents influence the regioselectively and extent of metallation, how metallated NHCs can activate small-molecules such as carbon dioxide, conditions which can lead to the metallation of N-dipp substitutents, as well as products and speciation following treatment of NHCs with a variety of bimetallic reagents.

In addition to expanding the knowledge of NHC reactivity, the work summarised in this review provides a reference and inspiration to researchers seeking to tailor NHCs for unique applications in synthesis and catalysis.

To find out more please read:

Polar organometallic strategies for regioselective C-H metallation of N-heterocyclic carbenes

Marina Uzelac and Eva Hevia.
Chem. Commun., 2018, Advance Article
DOI: 10.1039/c8cc00049b

About the author:

Comments Off on An Organometallic Toolbox for the Study and Synthesis of Unique N-Heterocyclic Carbenes

Capturing C60 in a Crystalline Copolymer Chain

12 Nov 2014

Since its structural realisation in 1985, C₆₀ has garnered much attention in the chemical world for not only its spherical shape, but also its stability, electronic properties and the ability to do chemistry on its surface.

One such avenue that has proven popular in recent times is the incorporation of C₆₀ into one-, two- and three-dimensional arrays, either covalently or non-covalently, in attempts to control the distribution of the molecules in the solid- or solution-phase. One problem that arises in the synthesis of these extended frameworks, however, is that there often a large amount of disorder and void space in the structure, so it can be difficult to ascertain with much degree of certainty how these C₆₀ molecules are oriented. This uncertainty can consequentially result in the properties and behaviours of the new materials remaining unidentified.

Now, researchers from the University of California, Davis – Marilyn Olmstead and Alan Balch – have shown that coordination chemistry can be used to not only generate polymers that covalently link molecules of functionalised C₆₀ in such a manner that can they can be studied crystallographically, but also that these polymers can be used to capture free C₆₀ and C₇₀.

Initially, polymers of C₆₀ were synthesised through the mono-functionalisation of C₆₀ with a piperazyl group, which, on account of its two tertiary amines, can coordinate in a linear fashion with transition metal ions, in this case rhodium(II) acetate. Upon the combination of these two components, a linear one-dimensional polymer was formed, in which it could be seen crystallographically that the C₆₀ moieties were positioned on alternating sides of the polymer chain. These polymer chains were further found to extend into two dimensions through the interdigitation of neighbouring chains in a zipper-like fashion. C60-Rh(II) polymers can capture free C60

Perhaps more interestingly is that when these polymer chains were synthesised in the presence of either C₆₀ or C₇₀, free molecules of C₆₀ or C₇₀ were seen to occupy the void spaces between the C₆₀ molecules of the polymer. Additionally, if a mixture of C₆₀ and C₇₀ was present in the polymer synthesis, it was observed that only C₆₀ was captured by the polymer, most likely as a result of a better geometric match between the polymer and the spherical C₆₀ in preference to the more elongated shape of C₇₀.

This work elegantly demonstrates the generation of not only a self-assembling C₆₀-containing polymer that can be characterised structurally in the solid state, but of one that can entrap free molecules of C₆₀ selectively over molecules of C₇₀. Based on the properties of free C₆₀ and transition metal complexes, the electronic and chromophoric properties of such a crystalline system could also be expected to offer some noteworthy results.

Read this HOT ChemComm article in full!

Zipping up fullerenes into polymers using rhodium(II) acetate dimer and N(CH₂CH₂)₂NC₆₀ as building blocks
Amineh Aghabali, Marilyn M. Olmstead and Alan L. Balch
Chem. Commun., 2014, Advance Article.
DOI: 10.1039/C4CC06995A

Biography

Anthea Blackburn is a guest web writer for Chemical Communications. Anthea is a graduate student hailing from New Zealand, studying at Northwestern University in the US under the tutelage of Prof. Fraser Stoddart (a Scot), where she is exploiting supramolecular chemistry to develop multidimensional systems and study the emergent properties that arise in these superstructures. When time and money allow, she is ambitiously attempting to visit all 50 US states before graduation.

Comments Off on Capturing C60 in a Crystalline Copolymer Chain

A new, functionally tolerant route to organo-aluminium reagents

13 Sep 2013

Paul Knochel and colleagues at the Ludwig Maximilians University in Munich have reported a new general synthesis of aryl and heteroaryl aluminium reagents. The route described allows a larger range of functional groups to be incorporated, compared with the more usual approach of inserting Al into aryl halide bonds directly. The synthetic methodology uses di-isobutyl aluminium chloride and n-BuLi at -78C in an exchange reaction with a functionalised aryl or heteroaryl halide.

General scheme for preparation and derivitisation of aryl aluminium reagents

The synthesis of a group of derivatives is described, via the reaction of the aluminium reagents with a variety of electrophiles. Typical cross coupling reactions using palladium catalysis, as well as copper-catalysed Michael additions, allylation and acylations are reported, involving a rich variety of incorporated functional groups. Importantly, further derivitisation of the organo-aluminium reagents includes no further transmetalation steps.

Of note are the reactivities of electron-rich furan and thiophene bromides functionalised with ester groups, which also could remain intact during the reaction with di-isobutylaluminium chloride and butyl-lithium at -78C, yielding the desired reagents that were further derivatised, as in other examples.

N-heterocycles such as 3-bromo-quinoline also received attention, yielding the aluminium reagent in 73% yield, and smoothly converting in a palladium catalysed cross coupling reaction with 4-iodobenzonitrile. Full NMR data for the products of the reactions described is given in the supplementary information.

In general, this Communication describes a considerable step forward in the field of organo-aluminium reagents for organic synthesis, and no doubt will be of interest to synthetic chemists in many fields.

Read this HOT ChemComm article today!

Generation of Functionalised Aryl and Heteroaryl Aluminium Reagents by Halogen/Lithium Exchange
Thomas Klatt, Klaus Groll and Paul Knochel
Chem. Commun., 2013,49, 6953-6955
DOI: 10.1039/C3CC43356K, Communication

Kevin Murnaghan is a guest web-writer for Chemical Communications. He is currently a Research Chemist in the Adhesive Technologies Business Sector of Henkel AG & Co. KGaA, based in Düsseldorf, Germany. His research interests focus primarily on enabling chemistries and technologies for next generation adhesives and surface treatments. Any views expressed here are his personal ones and not those of Henkel AG & Co. KGaA.

Comments Off on A new, functionally tolerant route to organo-aluminium reagents

Synthesising gold- and silver-NHC complexes using a weak base

24 Jun 2013

Scientists from the University of Zaragoza in Spain have developed a simple and efficient method of synthesising N-heterocyclic carbene (NHC) gold and silver complexes with the use of an extremely weak base¹.

Gold-NHC complexes are commercially important precursors of active, luminescent species that catalyse many useful reactions, such as cycloisomerisation, rearrangement of allylic acetates, C-H activation, carbene transfer, polymerisation, among others. In addition, they have potentially significant applications in the synthesis of new pharmaceuticals and natural products.

Conventional methods of gold-NHC synthesis– the generation of free NHC and the Ag-carbene transfer route– present several logistic and economic limitations, such as the need for an inert atmosphere and the use of additives. These methods are not always efficient, and typically require complicated working conditions in order to produce even moderate yields.

M. Concepción Gimeno and her team’s novel and elegant one-pot synthetic route involves isolating imidazolium salts using [AuCl(tht)] (tht = tetrahydrothiophene) in the presence of a mild base, such as K₂CO₃, to produce gold-NHC complexes with very high yields (91-94%) over relatively short reaction times (1.5 hours).

c3cc42919a-s2

Similarly, Gimeno et al. found that, using the same mild base protocol, silver-NHC complexes could also be efficiently synthesised using AgNO₃, with vast potential significance in transmetalation.

c3cc42919a-s3

In both routes, the reactions occur under ambient conditions, eliminating the need to work in an argon atmosphere, and using readily-available technical grade solvents.

Interestingly, a mere few days later, Gimeno et al.‘s groundbreaking work was followed closely and independently by a related Communication from Steven Nolan’s group at the University of St Andrews. In addition to testing a similar methodology, Nolan’s team compared small- and larger-scale reactions, and characterised compounds by ¹H and ¹³C{¹H} NMR spectroscopies, as well as by elemental analysis².

To find out more about these fascinating breakthroughs in organometallics, read these HOT ChemComm articles now for free!

1. Simple and efficient synthesis of [MCI(NHC)] (M = Au, Ag) complexes
Renso Visbal, Antonio Laguna and M. Concepción Gimeno
Chem. Commun., 2013, 49
DOI: 10.1039/C3CC42919A, Communication

2. Straightforward synthesis of [Au(NHC)X] (NHC = N-heterocyclic carbene, X = Cl, Br, I) complexes
Alba Collado, Adrián Gómez-Suárez, Anthony R. Martin, Alexandra M. Z. Slawin and Steven P. Nolan
Chem. Commun., 2013, 49
DOI: 10.1039/C3CC43076F, Communication

Comments Off on Synthesising gold- and silver-NHC complexes using a weak base

Chemical Communications Blog

Archive for the ‘Organometallics’ Category

Studying Anticancer Agents with XFM

Copper A3 Coupling using a Switchable Homogeneous/Heterogeneous Catalyst

Come for the colour changing crystals, stay for the science

An Organometallic Toolbox for the Study and Synthesis of Unique N-Heterocyclic Carbenes

Capturing C60 in a Crystalline Copolymer Chain

A new, functionally tolerant route to organo-aluminium reagents

Synthesising gold- and silver-NHC complexes using a weak base

Links

Categories

Archives

Meta