Synthesis of zigzag- and fjord-edged nanographene with dual amplified spontaneous emission

We report the synthesis of a dibenzodinaphthocoronene (DBDNC) derivative as a novel nanographene with armchair, zigzag, and fjord edges, which was characterized by NMR and X-ray crystallography as well as infrared (IR) and Raman spectroscopies. Ultrafast transient absorption (TA) spectroscopy revealed the presence of stimulated emission signals at 655 nm and 710 nm with a relatively long lifetime, which resulted in dual amplified spontaneous emission (ASE) bands under ns-pulsed excitation, indicating the promise of DBNDC as a near-infrared (NIR) fluorophore for photonics. Our results provide new insight into the design of nanographene with intriguing optical properties by incorporating fjord edges.

Dibenzo[a,m]dinaphtho[ef,hi]coronene with zigzag and fjord edges was synthesized and characterized, demonstrating a nonplanar structure with near-infrared stimulated emission with a relatively long lifetime and dual-amplified spontaneous emission.     

Flash chemistry enables high productivity metalation-substitution of 5-alkyltetrazoles

Tetrazoles play a prominent role in medicinal chemistry due to their role as carboxylate bioisosteres but have largely been overlooked as C–H functionalisation substrates. We herein report the development of a high-yielding and general procedure for the heterobenzylic C–H functionalisation of 5-alkyltetrazoles in up to 97% yield under batch conditions using a metalation/electrophilic trapping strategy. Through the use of thermal imaging to identify potentially unsafe exotherms, a continuous flow procedure using a flash chemistry strategy has also been developed, allowing products to be accessed in up to 95% yield. This enabled an extremely high productivity rate of 141 g h⁻¹ to be achieved on an entry-level flow system.

We report a α-metalation-substitution of readily deprotected 5-alkyltetrazoles under batch and continuous flow conditions. In flow, thermal imaging enabled identification of an unsafe exotherm and optimisation of a productivity rate of 141 g h⁻¹.     

C–H functionalisation tolerant to polar groups could transform fragment-based drug discovery (FBDD)

We have analysed 131 fragment-to-lead (F2L) examples targeting a wide variety of protein families published by academic and industrial laboratories between 2015–2019. Our assessment of X-ray structural data identifies the most common polar functional groups involved in fragment-protein binding are: N–H (hydrogen bond donors on aromatic and aliphatic N–H, amides and anilines; totalling 35%), aromatic nitrogen atoms (hydrogen bond acceptors; totalling 23%), and carbonyl oxygen group atoms (hydrogen bond acceptors on amides, ureas and ketones; totalling 22%). Furthermore, the elaboration of each fragment into its corresponding lead is analysed to identify the nominal synthetic growth vectors. In ∼80% of cases, growth originates from an aromatic or aliphatic carbon on the fragment and more than 50% of the total bonds formed are carbon–carbon bonds. This analysis reveals that growth from carbocentric vectors is key and therefore robust C–H functionalisation methods that tolerate the innate polar functionality on fragments could transform fragment-based drug discovery (FBDD). As a further resource to the community, we have provided the full data of our analysis as well as an online overlay page of the X-ray structures of the fragment hit and leads: https://astx.com/interactive/F2L-2021/

An in depth meta analysis of 131 fragment-to-lead case-studies has shown the importance of synthetic methods that allow carbon-centred synthetic elaboration in the presence of polar pharmacophores.     

Functionalised nanopores: chemical and biological modifications

Nanopore technology has established itself as a powerful tool for single-molecule studies. By analysing changes in the ion current flowing through a single transmembrane channel, a wealth of molecular information can be elucidated. Early studies utilised nanopore technology for sensing applications, and subsequent developments have diversified its remit. Nanopores can be synthetic, solid-state, or biological in origin, but recent work has seen these boundaries blurred as hybrid functionalised pores emerge. The modification of existing pores and the construction of novel synthetic pores has been an enticing goal for creating systems with tailored properties and functionality. Here, we explore chemically functionalised biological pores and the bio-inspired functionalisation of solid-state pores, highlighting how the convergence of these domains provides enhanced functionality.

The convergence of chemistry, biology, and solid-state approaches enables the construction hybrid nanopores with enhanced single-molecule applications.     

Mapping blood biochemistry by Raman spectroscopy at the cellular level

We report how Raman difference imaging provides insight on cellular biochemistry in vivo as a function of sub-cellular dimensions and the cellular environment. We show that this approach offers a sensitive diagnostic to address blood biochemistry at the cellular level. We examine Raman microscopic images of the distribution of the different hemoglobins in both healthy (discocyte) and unhealthy (echinocyte) blood cells and interpret these images using pre-calculated, accurate pre-resonant Raman tensors for scattering intensities specific to hemoglobins. These tensors are developed from theoretical calculations of models of the oxy, deoxy and met forms of heme benchmarked against the experimental visible spectra of the corresponding hemoglobins. The calculations also enable assignments of the electronic transitions responsible for the colour of blood: these are mainly ligand to metal charge transfer transitions.

We assign the electronic transitions responsible for the colour of blood and present a Raman imaging diagnostic approach for individual blood cells.     

Functionalisation of ethereal-based saturated heterocycles with concomitant aerobic C–H activation and C–C bond formation

With an ever-growing emphasis on sustainable synthesis, aerobic C–H activation (the use of oxygen in air to activate C–H bonds) represents a highly attractive conduit for the development of novel synthetic methodologies. Herein, we report the air mediated functionalisation of various saturated heterocycles and ethers via aerobically generated radical intermediates to form new C–C bonds using acetylenic and vinyl triflones as radical acceptors. This enables access to a variety of acetylenic and vinyl substituted saturated heterocycles that are rich in synthetic value. Mechanistic studies and control reactions support an aerobic radical-based C–H activation mechanism.

Herein we disclose a novel method for the aerobic C–H activation of ethereal-based heterocycles to generate various α-functionalised building blocks.     

On-surface cyclodehydrogenation reaction pathway determined by selective molecular deuterations

Understanding the reaction mechanisms of dehydrogenative C_aryl–C_aryl coupling is the key to directed formation of π-extended polycyclic aromatic hydrocarbons. Here we utilize isotopic labeling to identify the exact pathway of cyclodehydrogenation reaction in the on-surface synthesis of model atomically precise graphene nanoribbons (GNRs). Using selectively deuterated molecular precursors, we grow seven-atom-wide armchair GNRs on a Au(111) surface that display a specific hydrogen/deuterium (H/D) pattern with characteristic Raman modes. A distinct hydrogen shift across the fjord of C_aryl–C_aryl coupling is revealed by monitoring the ratios of gas-phase by-products of H₂, HD, and D₂ with in situ mass spectrometry. The identified reaction pathway consists of a conrotatory electrocyclization and a distinct [1,9]-sigmatropic D shift followed by H/D eliminations, which is further substantiated by nudged elastic band simulations. Our results not only clarify the cyclodehydrogenation process in GNR synthesis but also present a rational strategy for designing on-surface reactions towards nanographene structures with precise hydrogen/deuterium isotope labeling patterns.

Selective deuterations were exploited to synthesize graphene nanoribbons on Au(111) surface with a specific H/D pattern on edges, allowing the determination of cyclodehydrogenation reaction pathway within the framework of pericyclic reactions.     

Synthesis of octagon-containing molecular nanocarbons

Nanocarbons, such as fullerenes, carbon nanotubes, and graphenes, have long inspired the scientific community. In order to synthesize nanocarbon molecules in an atomically precise fashion, many synthetic reactions have been developed. The ultimate challenge for synthetic chemists in nanocarbon science is the creation of periodic three-dimensional (3D) carbon crystals. In 1991, Mackay and Terrones proposed periodic 3D carbon crystals with negative Gaussian curvatures that consist of six- and eight-membered rings (the so-called Mackay–Terrones crystals). The existence of the eight-membered rings causes a warped nanocarbon structure. The Mackay–Terrones crystals are considered a “dream material”, and have been predicted to exhibit extraordinary mechanical, magnetic, and optoelectronic properties (harder than diamond, for example). To turn the dream of having this wonder material into reality, the development of methods enabling the creation of octagon-embedding polycyclic structures (or nanographenes) is of fundamental and practical importance. This review describes the most vibrant synthetic achievements that the scientific community has performed to obtain curved polycyclic nanocarbons with eight-membered rings, building blocks that could potentially give access as templates to larger nanographenes, and eventually to Mackay–Terrones crystals, by structural expansion strategies.

Nanocarbons, such as fullerenes, carbon nanotubes, and graphenes, have long inspired the scientific community.     

A manganese(i)tricarbonyl-catalyst for near room temperature alkene and alkyne hydroarylation

Developing more efficient catalytic processes using abundant and low toxicity transition metals is key to enable their mainstream use in synthetic chemistry. We have rationally designed a new Mn(i)-catalyst for hydroarylation reactions that displays much improved catalytic activity over the commonly used MnBr(CO)₅. Our catalyst, MnBr(CO)₃(MeCN)₂, avoids the formation of the off-cycle manganacycle-(CO)₄ species responsible for low catalyst activity, allowing near room temperature hydroarylation of alkenes and alkynes with broad functional group tolerance including late stage functionalisation and diversification of bioactive molecules.

A Mn(i)-catalyst for hydroarylation reactions, MnBr(CO)₃(MeCN)₂, avoids the formation of the off-cycle manganacycle-(CO)₄ species responsible for low catalyst activity typical of MnBr(CO)₅, leading to mild and broad scope hydroarylation.     

Fluorine in metal-catalyzed asymmetric transformations: the lightest halogen causing a massive effect

This review aims at providing an overview of the most significant applications of fluorine-containing ligands reported in the literature starting from 2001 until mid-2021. The ligands are classified according to the nature of the donor atoms involved. This review highlights both metal–ligand interactions and the structure–reactivity relationships resulting from the presence of the fluorine atom or fluorine-containing substituents on chiral catalysts.

This review provides an overview of the most significant applications of fluorine-tagged ligands, including metal–ligand interactions, structure–reactivity relationships, and transition state models, in metal-catalyzed asymmetric transformations.     

X-ray spectroscopy study of lithiated graphite obtained by thermal deposition of lithium

X-ray photoelectron spectroscopy (XPS), X-ray emission spectroscopy (XES), and near edge X-ray absorption fine structure (NEXAFS) spectroscopy are used for in situ studies of the electronic structure of lithiated natural graphite produced by thermal deposition of lithium upon graphite in a vacuum. By XPS and NEXAFS spectroscopy it is found that lithium vapor thermal deposition results in the formation of a lithiated graphite surface layer and a change in its electronic structure. Based on the quantum chemical simulation of the experimental СK_α XES spectrum of lithiated graphite, it is found that lithium atoms are located mostly on the edges of graphite crystallites. Atomic force microscopy reveals that the size of natural graphite flakes varies from 50 nm to 200 nm.     

Palladium-catalyzed difluoroalkylative carbonylation of styrenes toward difluoropentanedioates

The introduction of fluorine atoms into organic molecules is an attractive but challenging topic. In this work, an interesting palladium-catalyzed difluoroalkylative carbonylation of aryl olefins has been developed. A wide range of aryl olefins were transformed into the corresponding difluoropentanedioate compounds with good functional-group tolerance and excellent regioselectivity. Inexpensive ethyl bromodifluoroacetate acts both as a difluoroalkyl precursor and a nucleophile here. Additionally, a scale–up reaction was also performed successfully, and further transformations of the obtained product were shown as well.

An interesting palladium-catalyzed difluoroalkylative carbonylation of aryl olefins has been developed. A wide range of aryl olefins were transformed into the corresponding difluoropentanedioate compounds with good functional-group tolerance and excellent regioselectivity.     

Ni single atoms on carbon nitride for visible-light-promoted full heterogeneous dual catalysis

Visible-light-driven organic transformations are of great interest in synthesizing valuable fine chemicals under mild conditions. The merger of heterogeneous photocatalysts and transition metal catalysts has recently drawn much attention due to its versatility for organic transformations. However, these semi-heterogenous systems suffered several drawbacks, such as transition metal agglomeration on the heterogeneous surface, hindering further applications. Here, we introduce heterogeneous single Ni atoms supported on carbon nitride (NiSAC/CN) for visible-light-driven C–N functionalization with a broad substrate scope. Compared to a semi-heterogeneous system, high activity and stability were observed due to metal–support interactions. Furthermore, through systematic experimental mechanistic studies, we demonstrate that the stabilized single Ni atoms on CN effectively change their redox states, leading to a complete photoredox cycle for C–N coupling.

In this work, the first demonstration of heterogeneous photoredox C–N coupling is reported using Ni atoms on C₃N₄. Due to metal–support interactions, high activity and stability were observed during visible-light-driven C–N functionalization.     

Ultrafast coherent photoexcited dynamics in a trimeric dendrimer probed by X-ray stimulated-Raman signals

The photoinduced ultrafast coherent inter-chromophore energy redistribution in a triarylamine trimer is explored using nonadiabatic excited state molecular dynamics followed by simulations of X-ray Raman signals. The nitrogencentered system ensures strong interchromophore interactions and, thus, the presence of coherences. Nevertheless, the multitude of non-deterministic photoinduced pathways during the ultrafast inter-branch migration of the excitation results in random confinement on some branches and, therefore, spatial exciton scrambling and loss of phase information at long times. We show that the vibronic coherence dynamics evolving into the incoherent scrambling mechanism on ultrafast 50 fs timescale, is accurately probed by the TRUECARS X-ray stimulated Raman signal. In combination with previous results, where the technique has revealed long-lived coherences in a rigid heterodimer, the signal is most valuable for detecting ultrafast molecular coherences or their absence. We demonstrate that X-ray Raman spectroscopy is a useful tool in the chemical design of functional molecular building blocks.

The photoinduced ultrafast coherent inter-chromophore energy redistribution in a triarylamine trimer is explored using nonadiabatic excited state molecular dynamics followed by simulations of X-ray Raman signals.     

Coordination unsaturation of vanadium nitride quantum dots boosts low-temperature aerobic oxidation of thiophenic sulfides

Aerobic oxidative desulfurization (AODS) promises a sustainable alternative technology for diesel desulfurization, which necessitates the efficient aerobic oxidation of thiophenic sulfides under mild conditions to minimize energy input, yet being longstandingly plagued by the grand challenge in low-temperature activation of triplet oxygen. Here we synthesize vanadium nitride quantum dots on graphene to controllably create coordination-unsaturated edge/corner V sites for boosting the AODS reaction. The catalyst activates the reaction at 70 °C, and is two orders of magnitude more active than the best V-based catalysts. We demonstrate through computational studies that the low-coordinated edge/corner V sites can effectively activate oxygen and adsorb sulfides to lower the activation barrier, dramatically enhancing the activity. The catalyst achieves deep AODS of real diesel at 80 °C with negligible attenuation in successive reuses, which highlights its attractive industrial potential. These findings provide scientific and practical insights to develop high-performance catalysts for a sustainable AODS process.

Vanadium nitride quantum dots are immobilized on graphene to controllably create coordination-unsaturated edge/corner V sites for the efficient aerobic oxidation of thiophenic sulfides.     

Charge transport through single-molecule bilayer-graphene junctions with atomic thickness

The van der Waals interactions (vdW) between π-conjugated molecules offer new opportunities for fabricating heterojunction-based devices and investigating charge transport in heterojunctions with atomic thickness. In this work, we fabricate sandwiched single-molecule bilayer-graphene junctions via vdW interactions and characterize their electrical transport properties by employing the cross-plane break junction (XPBJ) technique. The experimental results show that the cross-plane charge transport through single-molecule junctions is determined by the size and layer number of molecular graphene in these junctions. Density functional theory (DFT) calculations reveal that the charge transport through molecular graphene in these molecular junctions is sensitive to the angles between the graphene flake and peripheral mesityl groups, and those rotated groups can be used to tune the electrical conductance. This study provides new insight into cross-plane charge transport in atomically thin junctions and highlights the role of through-space interactions in vdW heterojunctions at the molecular scale.

Charge transport through single-molecule bilayer-graphene junctions fabricated by a cross-plane break junction technique can be tuned at the atomic level.     

Calix[4]pyrrolato gallate: square planar-coordinated gallium(iii) and its metal–ligand cooperative reactivity with CO2 and alcohols

Forcing a priori tetracoordinate atoms into planar configuration represents a promising concept for enhanced reactivity of p-block element-based systems. Herein, the synthesis, characterization, and reactivity of calix[4]pyrrolato gallates, constituting square planar-coordinated gallium(iii) atoms, are reported. Unusual structural constraint-induced Lewis acidity against neutral and anionic donors is disclosed by experiment and rationalized by computations. An energetically balanced dearomatization/rearomatization of a pyrrole unit enables fully reversible metal–ligand cooperative capture of CO₂. While alcohols are found unreactive against the gallates, a rapid and selective OH-bond activation can be triggered upon protonation of the ligand. Secondary ligand–sphere modification adds a new avenue to structurally-constrained complexes that unites functional group tolerance with unconventional reactivity.

Ideally square-planar coordinated gallium(iii) species is isolated and fully characterized. Spontaneous metal–ligand cooperative reactivity towards CO₂ is observed, while OH-bond activation of alcohols can be triggered by protonation of the ligand.     

Lipase-catalyzed esterification in water enabled by nanomicelles. Applications to 1-pot multi-step sequences

Esterification in an aqueous micellar medium is catalyzed by a commercially available lipase in the absence of any co-factors. The presence of only 2 wt% designer surfactant, TPGS-750-M, assists in a 100% selective enzymatic process in which only primary alcohols participate (in a 1 : 1 ratio with carboxylic acid). An unexpected finding is also disclosed where the simple additive, PhCF₃ (1 equiv. vs. substrate), appears to significantly extend the scope of usable acid/alcohol combinations. Taken together, several chemo- and bio-catalyzed 1-pot, multi-step reactions can now be performed in water.

Esterification in an aqueous micellar medium is catalyzed by a commercially available lipase in the absence of any co-factors.     

Defect-engineered surfaces to investigate the formation of self-assembled molecular networks

Herein we report the impact of covalent modification (grafting), inducing lateral nanoconfinement conditions, on the self-assembly of a quinonoid zwitterion derivative into self-assembled molecular networks at the liquid/solid interface. At low concentrations where the compound does not show self-assembly behaviour on bare highly oriented pyrolytic graphite (HOPG), close-packed self-assembled structures are visualized by scanning tunneling microscopy on covalently modified HOPG. The size of the self-assembled domains decreases with increasing the density of grafted molecules, i.e. the molecules covalently bound to the surface. The dynamics of domains are captured with molecular resolution, revealing not only time-dependent growth and shrinkage processes but also the orientation conversion of assembled domains. Grafted pins play a key role in initiating the formation of on-surface molecular self-assembly and their stabilization, providing an elegant route to study various aspects of nucleation and growth processes of self-assembled molecular networks.

We showcase the use of covalently modified HOPG for the investigation of domain size controlled 2D self-assembly, nucleation and growth kinetics, molecular adsorption/desorption thermodynamics, and tip-induced selective recrystallization.     

Pyrimidine-directed metal-free C–H borylation of 2-pyrimidylanilines: a useful process for tetra-coordinated triarylborane synthesis

Convenient, easily handled, laboratory friendly, robust approaches to afford synthetically important organoboron compounds are currently of great interest to researchers. Among the various available strategies, a metal-free approach would be overwhelmingly accepted, since the target boron compounds can be prepared in a metal-free state. We herein present a detailed study of the metal-free directed ortho-C–H borylation of 2-pyrimidylaniline derivatives. The approach allowed us to synthesize various boronates, which are synthetically important compounds and various four-coordinated triarylborane derivatives, which could be useful in materials science as well as Lewis-acid catalysts. This metal-free directed C–H borylation reaction proceeds smoothly without any interference by external impurities, such as inorganic salts, reactive functionalities, heterocycles and even transition metal precursors, which further enhance its importance.

We present the metal-free ortho-C–H borylation of 2-pyrimidylanilines to afford synthetically important boronic esters and tetra-coordinated triarylboranes, which could be useful in materials science as well as Lewis-acid catalysts.