Chemical Science Blog

Activating a bond is the first step towards bond breaking processes for synthesis and catalysis. Despite the major role of transition metals in a variety of bond activation processes, C–X bond activation of halogenated benzenes (PhX, X = F, Cl, Br, I) is still challenging; there are very few examples of metal···XPh complexes, even though they are crucial for C–X bond activation and catalysis. There are even fewer examples of main group metal···XPh complexes, with no examples of main group complexes of bromobenzene or iodobenzene.

Researchers in Germany have been studying cationic magnesium complexes with the β-diketiminate ligand (^RBDI, R = methyl or t-butyl), where their extreme Lewis acidity makes them ideal candidates for halobenzene complex formation for C–X activation. Building upon their previous findings of the formation of a Mg-chlorobenzene complex, the researchers have now demonstrated the preparation of the full series of halobenzene complexes, including the first examples of coordination of bromobenzene and iodobenzene to a main group metal, as shown in Scheme 1.

Scheme 1. Syntheses of Mg-XPh complexes (X = F, Cl, Br, I)

The researchers found that both the smaller methyl-substituted complex, (^MeBDI)Mg⁺, and the bulkier t-butyl substituted complex, (^tBuBDI)Mg⁺, were able to bind fluorobenzene to form Mg···FPh complexes (1–3 in, Scheme 1), owing to the high polarity of PhF that can compete with the Mg···B(C₆F₅)₄^–  (the magnesium–anion) interaction. The other halobenzene complexes (Mg···XPh for X = Cl, Br, I; VI, 4, 5) could only be accessed with the use of the bulkier ^tBuBDI ligand. This was attributed to the fact that the bulky t-butyl substituents essentially turn off the Mg···B(C₆F₅)₄^– interaction, which in turn allows the less polar PhX halobenzenes to bind to the magnesium centre.

The researchers isolated and fully characterised the Mg-halobenzene complexes, and used X-ray crystallography and DFT calculations to further understand their properties. The interaction of the strongly Lewis acidic (BDI)Mg⁺ cation with the halobenzene resulted in C–X activation as shown by elongation of the C–X bonds in the crystal structures. Additionally, the solid-state structures showed that the Mg···X–Ph angle is the most linear for PhF and decreases in size (i.e. bends more) for the larger halogens. This increased bending for the larger halogens is explained by the halogen σ-hole, which is a region of positive electrostatic potential on the surface of the halogen opposite to the C–X bond, that increases with halogen size. As shown by the schematic in Figure 1, the presence of a larger halogen hole forces a more acute Mg···X interaction relative to the C–X bond.

Figure 1. Top: Schematic showing the halogen σ-hole (red = positive electrostatic potential, blue = negative electrostatic potential), with possible coordination sites for Mg. Bottom: Electrostatic maps for the halobenzenes.

DFT calculations were also performed and were in good agreement with the solid-state experimental parameters. The researchers calculated complexation enthalpies between 11 and 13 kcal mol^-1, which are weak but still indicate a Mg···X–Ph interaction. This interaction ultimately indicates C–X bond activation, signifying that these main group complexes show potential for C–X bond breaking processes in future catalytic applications.

To find out more, please read:

Magnesium–halobenzene bonding: mapping the halogen sigma-hole with a Lewis-acidic complex

Alexander Friedrich, Jürgen Pahl, Jonathan Eyselein, Jens Langer, Nico van Eikema Hommes, Andreas Görling and Sjoerd Harder*

Chem. Sci., 2021, Advance Article

About the blogger:

Dr. Samantha Apps recently finished her post as a Postdoctoral Research Associate in the Lu Lab at the University of Minnesota, USA, and obtained her PhD in 2019 from Imperial College London, UK. She has spent the last few years, both in her PhD and postdoc, researching synthetic nitrogen fixation and transition metal complexes that can activate and functionalise dinitrogen. Outside of the lab, you’ll likely find her baking at home, where her years of synthetic lab training has sparked a passion in kitchen chemistry too.

Hydrogen bonding is all around us. The intermolecular force of attraction between a hydrogen atom bound to an electronegative centre (the hydrogen bond donor, HBD) and another nearby electronegative atom with a lone pair of electrons (the hydrogen bond acceptor, HBA) is present in many chemical structures and can be seen in many biological motifs such as in enzymes or proteins. Beyond a simple HBD-HBA pair (Figure 1a), hydrogen bonding can cascade between multiple HBD-HBA pairs (Figure 1b). In these paired units, the presence of a central proton mediator (e.g. imidazole) can induce polarisation to make the resulting hydrogen bonds stronger, promoting further reactivity and selectivity (Figure 1c).

Figure 1. Hydrogen bonding between donor (D) and acceptor (A) atoms, with the net dipole shown by the arrows beneath. (a) Simple HBD-HBA pair. (b) Cascade hydrogen bonding around a central imidazole proton mediator, that can promote further reactivity with a larger net additive dipole (c).

Some enzymes cleverly make use of cascade hydrogen bonding to control the strength of the hydrogen bonds that form between the limited number of available amino acids. One example is a class of enzymes with a ‘catalytic triad’, whereby a hydrogen bonding array exists between the hydroxyl group of serine, the imidazole group of histidine and the carboxylate group of aspartate residues (Figure 2a). Researchers from South Korea took inspiration from such catalytic triads to create a ‘synthetic triad’ with a biomimetic hydrogen bonding network (Figure 2b, compound 1). The researchers employed a central benzimidazole to their synthetic triad to act as a platform to align the HBD-HBA pairs, instead of the precise three-dimensional structure that would anchor these pairs in enzymes.

Figure 2. (a) Chemical (left) and X-ray (right) structures of the ‘catalytic triad’ in the active site of the enzyme serine protease. (b) Chemical structure (left) and computational model (right) of the ‘synthetic triad’ designed by the researchers.

The researchers envisioned that their biomimetic small molecule could be used as a fluorescent probe owing to the photophysical properties of the chosen benzimidazole motif. They designed the probe for cyanide detection, where capture of a toxic cyanide ion turns on fluorescence in the probe (Figure 3c). The design of the probe was therefore influenced with the target application in mind, so the researchers systematically added each HBD-HBA pair around the benzimidazole, as shown in Figure 3b.

Figure 3. (a) Cascade hydrogen bonding around a benzimidazole core. (b) The systematic design of the probe, starting from one HBD-HBA pair up to four pairs. (c) Mechanism of capture of the cyanide ion to turn on fluorescence.

An aldehyde functional group was selected for the first HBD-HBA pair, due to its ability to form hydrogen bonds that can quench the fluorescence in the absence of cyanide (compound 2). The researchers tested compound 2 for cyanide detection and indeed observed fluorescence, but found that the fluorescence also occurred in the presence of a simple Brønsted base. The design of the probe was then iteratively modified until fluorescence was selective for cyanide addition, with a total of four HBD-HBA pairs around the benzimidazole centre that mutually reinforced one another. This strategy shows promise for the design of other fluorescent probes and could also be utilised for other biological targeting applications.

To find out more, please read:

Biomimetic hydrogen-bonding cascade for chemical activation: telling a nucleophile from a base

Hyunchang Park and Dongwhan Lee*

Chem. Sci., 2021, Advance Article

About the blogger:

Dr. Samantha Apps recently finished her post as a Postdoctoral Research Associate in the Lu Lab at the University of Minnesota, USA, and obtained her PhD in 2019 from Imperial College London, UK. She has spent the last few years, both in her PhD and postdoc, researching synthetic nitrogen fixation and transition metal complexes that can activate and functionalise dinitrogen. Outside of the lab, you’ll likely find her baking at home, where her years of synthetic lab training has sparked a passion in kitchen chemistry too.

We are pleased to share a selection of our referee-recommended HOT articles for December. We hope you enjoy reading these articles and congratulations to all the authors whose articles are featured! As always, Chemical Science is free to read & download. You can find our full 2020 HOT article collection here.

Efficacy analysis of compartmentalization for ambient CH₄ activation mediated by a Rh^II metalloradical in a nanowire array electrode
Benjamin S. Natinsky, Brandon J. Jolly, David M. Dumas and Chong Liu
Chem. Sci., 2021, Advance Article
DOI: 10.1039/D0SC05700B, Edge Article

Supertetrahedral polyanionic network in the first lithium phosphidoindate Li₃InP₂ – structural similarity to Li₂SiP₂ and Li₂GeP₂ and dissimilarity to Li₃AlP₂ and Li₃GaP₂
Tassilo M. F. Restle, Volker L. Deringer, Jan Meyer, Gabriele Raudaschl-Sieber and Thomas F. Fässler
Chem. Sci., 2021, Advance Article
DOI: 10.1039/D0SC05851C, Edge Article

One class classification as a practical approach for accelerating π–π co-crystal discovery
Aikaterini Vriza, Angelos B. Canaj, Rebecca Vismara, Laurence J. Kershaw Cook, Troy D. Manning, Michael W. Gaultois, Peter A. Wood, Vitaliy Kurlin, Neil Berry, Matthew S. Dyer and Matthew J. Rosseinsky
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DOI: 10.1039/D0SC04263C, Edge Article

Fast reversible isomerization of merocyanine as a tool to quantify stress history in elastomers
Yinjun Chen, C. Joshua Yeh, Qiang Guo, Yuan Qi, Rong Long and Costantino Creton
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DOI: 10.1039/D0SC06157C, Edge Article

Peptide sequence mediated self-assembly of molybdenum blue nanowheel superstructures
Shan She, Weimin Xuan, Nicola L. Bell, Robert Pow, Eduard Garrido Ribo, Zoe Sinclair, De-Liang Long and Leroy Cronin
Chem. Sci., 2021, Advance Article
DOI: 10.1039/D0SC06098D, Edge Article

Enhanced voltammetric anion sensing at halogen and hydrogen bonding ferrocenyl SAMs
Robert Hein, Xiaoxiong Li, Paul D. Beer and Jason J. Davis
Chem. Sci., 2021, Advance Article
DOI: 10.1039/D0SC06210C, Edge Article

Magnesium–halobenzene bonding: mapping the halogen sigma-hole with a Lewis-acidic complex
Alexander Friedrich, Jürgen Pahl, Jonathan Eyselein, Jens Langer, Nico van Eikema Hommes, Andreas Görling and Sjoerd Harder
Chem. Sci., 2021, Advance Article
DOI: 10.1039/D0SC06321E, Edge Article

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