Abstract Head and neck squamous cell carcinoma (HNSCC) remains difficult to treat without substantial functional and cosmetic morbidity, as current management relies largely on surgery, radiation, and chemotherapy. However, these approaches often fail to achieve effective tumor control in therapy-resistant HNSCC. Photodynamic therapy (PDT) has strong potential for HNSCC treatment because it enables spatially restricted tumor ablation while limiting damage to surrounding healthy tissue. Here, we apply a near-infrared (NIR) cyanine–carborate photosensitizer (PS) platform to HNSCC to identify a redox-based mechanism that limits PDT response in resistant cells and evaluate a strategy for sensitizing resistant cells. Using complementary human papillomavirus (HPV)-positive and -negative HNSCC models, we show that PDT induces acute oxidative stress and lipid peroxidation in both sensitive and resistant cells. However, resistant cells counter this stress through an adaptive redox response marked by increased xCT (SLC7A11)-dependent cystine utilization. This response sustains glutathione-linked antioxidant buffering, limits lipid peroxidation, and promotes survival under PDT. Genetic or pharmacologic disruption of cystine uptake prevents this adaptive defense, restores oxidative vulnerability, and sensitizes PDT-resistant HNSCC cells to treatment. Consistent with these mechanistic findings, cyanine–carborate-induced PDT with xCT (SLC7A11) inhibition markedly suppressed tumor growth in vivo. Together, these findings identify xCT-dependent cystine metabolism as a targetable vulnerability for therapeutic sensitization of resistant HNSCC to PDT.

The so-called anode-less cell configuration presents an advanced approach to increase energy density beyond intrinsic Na metal anode cells due to in-situ formation of the alkali metal film which is decoupled from initial anode weights. Simultaneously, this technology inherently overcomes the challenges and safety concerns associated with the processing of highly reactive materials during cell assemblies. The availability of sodium precursor supply chains and the natural high crustal abundance suggests that the anode-free sodium battery (AFSB) is a very attractive chemistry. However, longevity (long, stable cycling) issues associated with coulombic inefficiency, side reactions, and dendritic sodium nucleation represents a barrier to realizing this technology. The highly reversible electrochemistry demanded of these systems is as intriguing from a fundamental perspective as they are practical. Currently, AFSB electrochemistry requires some novel chemical and/or architectural current collector modification to enhance the efficiency of metal electro-plating/stripping and sustain cycling over long periods of time. To this end, engineered sodiophilic surfaces have proven a successful strategy to promote favorable metal nucleation and cycling. However, little variation in electrolyte chemistries beyond NaPF 6 /glyme compositions have been adequately explored. Here, we explore the benefits of incorporating the [HCB 9 H 9 ] - carborane cluster as the anionic electrolyte component in AFSBs. We find the fluorine-free carboranyl electrolyte imparts substantial improvements over NaPF 6 electrolytes without the need to introduce engineered current collector surfaces. How the inherent properties of the anion translate to favorable electrochemical behavior in anode-free cell configurations will be presented. This includes commentary on the sodium nucleation mechanisms and consequences of the interphasial chemistry imparted by the electrolyte. Substantial performance improvements in a high cathode loading full cell are demonstrated that suggests electrolyte design is one of the most important facets in implementing AFSBs.

Photodynamic therapy (PDT) has emerged as a promising targeted treatment for cancer. However, current PDT is limited by low tissue penetration, insufficient phototoxicity (toxicity with light irradiation), and undesirable cytotoxicity (toxicity without light irradiation). Here, we report the discovery of cyanine-carborane salts as potent photosensitizers (PSs) that harness the near-infrared (NIR) absorbing [cyanine+] with the inertness of [carborane-]. The implementation of [cyanine+] [carborane-] salts dramatically enhance cancer targeting of the PSs and decrease cytotoxicity. We characterize the cellular uptake of the cyanine-carborane PSs, organelle localization, generation of reactive oxygen species (ROS) with the ability to cogenerate multiple ROS species, suppression of pro-metastatic pathways, and activation of apoptotic pathways. We further demonstrate the ability of optimized PSs to eliminate tumors in vivo using an orthotopic mouse model of breast cancer. These newly developed [cyanine+] [carborane-] salt PSs introduce a potent therapeutic approach against aggressive breast cancer while decreasing side effects.

For anode-free sodium batteries to achieve practical consideration, highly reversible chemistries require exceptional >= 99.95% coulombic efficiencies that maintain over prolonged cycling periods. To do so, consumption of this severely limited sodium inventory must be restricted while metal nucleation processes that comprise the in situ formed metal anode are improved. Herein, we describe a fluorine-free carborane electrolyte that satisfies these criteria by emphasizing reductive stability and weakly coordinating anion behavior as design principles. We find this approach promotes the development of a thin, robust SEI chemistry rich in both organic speciation and boron. The electrolyte described herein exhibits ideal metal nucleation behavior on one-micron thin carbonaceous current collector surfaces and achieves a metal deposition/stripping efficiency near parity for 400 cycles. This novel anode chemistry is introduced to anode-free full cell configurations where 87% of the initial discharge capacity is retained after 1000 cycles at 2.0 C. Post-test characterization of deep-cycled anode-free cells reveals suppressed capacity fade in these systems is attributed to the chemical stability of the carborane anion.

Borohydrides are important molecular entities for a myriad of applications from organic synthesis to components of functional materials and devices. All borohydrides have been thought to be susceptible to spontaneous ignition when exposed to a flame. Herein we demonstrate that this is not always true by identifying several borohydride rich materials that are resistant to combustion when contacted with a torch. One of these materials is a Li+ salt of a carborane anion that depending on its coordination environment exists as a unique ionic liquid that has a nearly naked Li+ countercation. This has provided us with the first opportunity to spectroscopically probe the interactions of such carborane anions with Li metal in a solvent free environment. We found that this carborane anion is immune to deleterious reduction at Li-metal surfaces, as evidenced by XPS, EDS and SEM analysis of the Li-Metal surface after exposure to the ionic liquid. Additionally, NMR analysis of the ionic liquid after stirring it with Li powder shows no reaction. Calculations show that the cage skeleton is reduced at the surface monolayer, but as the reduced form is removed from contact with Li-metal, the cage reverts to the closo-form, demonstrating reversibility.

Polyhalogenated closo-12-vertex carborane anions are thought to be inert species incapable of participating in direct B-X substitution reactions. Here, we show that this is not true and that such species can be easily coaxed into intramolecular cross-coupling cyclizations without the need for a catalyst. When cage C-tethered O and N-heteroallylic anions are generated, a variety of cyclized products can be formed in high yield under mild conditions. Additionally, we show that even C-tethered neutral nucleophiles, such as the pyridine moiety, undergo facile B-X substitution chemistry and these reactions are not dependent on the countercation. Serendipitously, we also found that when these cyclizations are attempted with acetamide derivatives, an unprecedented cluster C-B bond scission reaction occurs, producing an unprecedented oxoborane stabilized by multicentered bonding. Amazingly this molecule can be protonated, leading to reformation of the C-B bond and cluster reorganization, and this process is reversible.

In 1958, Breslow proposed that the coenzyme thiamine, also known as vitamin B1, acted as a source of transient carbenes that facilitated the catalytic activity of various important enzymes. This was a controversial hypothesis, as, then and still now, carbenes are believed to be incompatible with water. Although evidence such as deuterium labeling experiments and the trapping of the so-called Breslow intermediate support Breslow's hypothesis, no spectroscopic evidence has ever been presented to prove that carbenes can exist or be generated in water. In this study, we disclose the synthesis and complete spectroscopic characterization by nuclear magnetic resonance and a single-crystal structure of a carbene that can be generated in water and isolated as a stable species, thus unambiguously validating Breslow's visionary hypothesis.

In the hands of experts, microcrystal electron diffraction (microED, a 3D ED method) is a powerful tool for structural chemistry and chemical discovery. To expand the accessibility and utility of microED, we introduce Reciprocal Eyes (REyes), an autonomous and intelligent platform (available for academic use) that combines diffraction-based particle selection with real-time data processing to deliver crystal structures without human intervention. REyes spatially maps diffraction signal and autonomously selects crystallites of interest, relying on lattice-quality metrics to acquire and index high-resolution data sets from diverse compounds. Tested on four different transmission electron microscopes (TEMs), it consistently yields preliminary ab initio structural solutions from single crystallites of materials, peptides, metal complexes, natural products (NPs), and proteins.

In the 1970s Hawthorne reported an electrochemical dehydrocoupling reaction of the closo-carborane anion [HCB9H91-] 1 to form the biscarborane [C2B18H182-] 2. In this Communication we show that the said "Hawthorne Reaction" can be achieved thermally and that it tolerates C-butylation. The new compound 2butyl was fully characterized by 11B, 1H, and 13C NMR spectroscopies, high-resolution mass spectrometry, and single-crystal X-ray diffraction. One interesting caveat is that 2 or 2butyl only form thermally when they are salts of Li+ and not NEt4+, Na+, K+, or Cs+. This observation means that Li+ in some way facilitates this process, introducing a new kind of Li+ effect.

To realize an energy storage transition beyond Li-ion competitive technologies, earth-abundant elements, such as Mg, are needed. Carborane anions are particularly well-suited to realizing magnesium-ion batteries (MIBs), as their inert and weakly coordinating properties beget excellent electrolyte performance. However, utilizing these materials in actual electrochemical cells has been hampered by the reliance on the Mg2+ salts of the commercially available [HCB11H11]- anion, which is not soluble in more weakly binding solvents apart from the higher glymes. Herein, we demonstrate it is possible to iteratively engineer the [HCB11H11]- anion surface synthetically to address previous solubility issues and yield a highly conductive (up to 7.33 mS cm-1) and electrochemically stable (up to +4.2 V vs Mg2+/0) magnesium electrolyte that surpasses the state of the art. This novel non-nucleophilic electrolyte exhibits highly dissociative behavior regardless of concentration and is tolerant of prolonged periods of cycling in symmetric cells at high current densities (up to 2.0 mA cm-2, 400 h). The hydrocarbon functionalized carborane electrolyte presented here demonstrates >96% Coulombic efficiency when paired with a Mo6S8 cathode. This approach realizes a needed candidate to discover next-generation cathode materials that can enable the design of practical and commercially viable Mg batteries.

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

The structural determination of natural products (NPs) can be arduous due to sample heterogeneity. This often demands itera-tive purification processes and characterization of complex molecules that may only be available in miniscule quantities. Microcrystal electron diffraction (microED) has recently shown promise as a method to solve crystal structures of NPs from nanogram quantities of analyte. However, its implementation in NP discovery remains hampered by sample throughput and purity requirements akin to traditional NP-discovery workflows. In the methods described herein, we leverage the resolving power of transmission electron microscopy (TEM) and the miniaturization capabilities of DNA microarray technology to address these challenges through the establishment of an NP screening platform, array electron diffraction (ArrayED). In this workflow, an array of HPLC fractions taken from crude extracts are deposited onto TEM grids in picoliter-sized droplets. This multiplexing of analytes on TEM grids enables 1200 or more unique samples to be simultaneously inserted into a TEM equipped with an autoloader. Selected area electron diffraction analysis of these microarrayed grids allows for rapid identification of crystalline metabolites. In this study, ArrayED enabled structural characterization of 14 natural products, including four novel crystal structures and two novel polymorphs, from 20 crude extracts. Moreover, we identify several chemical species that would not be detected by standard mass spectrometry (MS) or UV/Vis and crystal forms that would not be characterized using traditional methods.

Ferrocene 1 and its dianionic Fe(bis)(dicarbollide) analogue 2 are classical compounds that display unusual stability. These compounds are not known to undergo transmetallation chemistry of the Fe-center and have been used extensively as chemical building blocks with consistent integrity. In this manuscript we describe the preparation of a charge compensated Fe(bis)(dicarbollide) species 3 Fe and its unprecedented transmetallation chemistry to Ir. Such reactions are hitherto unknown for any transition metal metallocene or metallacarborane complex. Additionally, we show that 3 Fe can be deprotonated to afford the corresponding bis(NHC) Li-carbenoid 5 that also displays unique reactivity. When 5 is reacted with [Ir(COD)Cl] 2 it also undergoes a rapid transmetallation of the ferrocene “like” core to afford 6 but with the added twist that the Li-carbenoid moiety stays intact and does not transmetalate. However, when 6 is subsequently treated with CuCl, the Li-carbenoid transmetalates to Cu, which allows the controlled formation of the corresponding heterobimetallic Ir/Cu aggregate. Lastly, when Li-carbenoid 5 is treated directly with CuCl, a double transmetallation occurs from both Fe to Cu and Li-carbenoid to Cu, resulting in the trimetallic Cu cluster 8 . These novel reactions pave the way for new synthetic methods to build complicated polymetallic clusters in a controlled fashion.

C-H functionalization of undecahalogenated carborane anions, [HCB11X11-] (X = Cl, Br, I), is performed with Cs2CO3 in acetonitrile. We show that the requisite Cl, Br and I carborane dianions can all be efficiently accessed with Cs2CO3. The utilization of Cs2CO3 eliminates the complications associated with competing E2 elimination reactions providing an efficient, more functional group tolerant, and broader scope than previously reported. The ensuing functionalized cages provide potential synthons for constructing advanced materials and other molecular architectures for various applications.

Correction for ‘Cesium carbonate mediated C–H functionalization of perhalogenated 12-vertex carborane anions’ by Sergio O. Lovera et al., Chem. Commun., 2022, 58, 4060–4062, DOI: https://doi.org/10.1039/D2CC00173J.

Discovered by Knöth in 1964, the 10-vertex closo-carborane anion [HCB9H91-] is a classical bicapped square antiprism that contains an unusual pentacoordinate carbon center. Compared to its larger icosahedral cousin [HCB11H111-], few investigations have been made into its use as a weakly coordinating anion or as a ligand substituent. Here we show that it is possible to prepare both a dianionic N-heterocyclic carbene (NHC) Li+ adduct as well as a trianionic C-2, C-5 dilithio species featuring two 10-vertex carborane anion substituents. All compounds were characterized via multinuclear NMR spectroscopy, single crystal X-ray diffraction, and HRMS when possible.

In this first reaction, the authors express their opinion about the misgivings of CHN combustion analysis. These views are in reaction to the manuscript titled An International Study Evaluating Elemental Analysis.

Traditionally, weakly coordinating anions have been utilized as spectators that allow a more complete expression of an electrophile's acidity. In this chapter we survey all known ligand classes that contain a pendant weakly to moderately coordinating anion covalently linked to their architecture. The synthesis and applications of such species will be summarized as well as important specific examples of their catalytic and stoichiometric chemistry.

Realization of practical sodium metal batteries (SMBs) is hindered due to lack of compatible electrolyte components, dendrite propagation, and poor understanding of anodic interphasial chemistries. Chemically robust liquid electrolytes that facilitate both favorable sodium metal deposition and a stable solid-electrolyte interphase (SEI) are ideal to enable sodium metal and anode-free cells. Herein we present advanced characterization of a novel fluorine-free electrolyte utilizing the [HCB11H11](1-) anion. Symmetrical Na cells operated with this electrolyte exhibit a remarkably low overpotential of 0.032 V at a current density of 2.0 mA cm(-2) and a high coulombic efficiency of 99.5 % in half-cell configurations. Surface characterization of electrodes post-operation reveals the absence of dendritic sodium nucleation and a surprisingly stable fluorine-free SEI. Furthermore, weak ion-pairing is identified as key towards the successful development of fluorine-free sodium electrolytes.

Correction for 'Cesium carbonate mediated C-H functionalization of perhalogenated 12-vertex carborane anions' by Sergio O. Lovera et al., Chem. Commun., 2022, 58, 4060-4062, DOI: https://doi.org/10.1039/D2CC00173J.