SMART: A data reporting standard for mass spectrometry imaging By Ying Xi,Alexandria L. Sohn,Alena N. Joignant,Stephanie M. Cologna,Boone M. Prentice and David C. Muddiman

Mass spectrometry imaging (MSI) is an important analytical technique that simultaneously reports the spatial location and abundance of detected ions in biological, chemical, clinical, and pharmaceutical studies. As MSI grows in popularity, it has become evident that data reporting varies among different research groups and between techniques. The lack of consistency in data reporting inherently creates additional challenges in comparing intra- and inter-laboratory MSI data. In this tutorial, we propose a unified data reporting system, SMART, based on the common features shared between techniques. While there are limitations to any reporting system, SMART was decided upon after significant discussion to more easily understand and benchmark MSI data. SMART is not intended to be comprehensive but rather capture essential baseline information for a given MSI study; this could be within a study (e.g., effect of spot size on the measured ion signals) or between two studies (e.g., different MSI platform technologies applied to the same tissue type). This tutorial does not attempt to address the confidence with which annotations are made nor does it deny the importance of other parameters that are not included in the current SMART format. Ultimately, the goal of this tutorial is to discuss the necessity of establishing a uniform reporting system to communicate MSI data in publications and presentations in a simple format to readily interpret the parameters and baseline outcomes of the data.     

Steric,Electronic and Conformational Synergistic Effects in the Gold(I)-catalyzed α-C−H Bond Functionalization of Tertiary Amines**

Direct C−H bond functionalization is a useful strategy for the straightforward formation of C−C and C−Heteroatom bonds. In the present work, a unique approach for the challenging electrophilic Au-catalyzed α-C−H bond functionalization of tertiary amines is presented. Electronic, steric and conformational synergistic effects exerted by the use of a malonate unit in the substrate were key to the success of this transformation. This new reactivity was applied to the synthesis of tetrahydro-γ-carboline products which, under oxidative conditions, could be converted into valuable structural motifs found in bioactive alkaloid natural products.     

Influence of Potassium Metal-Support Interactions on Dendrite Growth

Combined synchrotron X-ray nanotomography imaging, cryogenic electron microscopy (cryo-EM) and modeling elucidate how potassium (K) metal-support energetics influence electrodeposit microstructure. Three model supports are employed: O-functionalized carbon cloth (potassiophilic, fully-wetted), non-functionalized cloth and Cu foil (potassiophobic, nonwetted). Nanotomography and focused ion beam (cryo-FIB) cross-sections yield complementary three-dimensional (3D) maps of cycled electrodeposits. Electrodeposit on potassiophobic support is a triphasic sponge, with fibrous dendrites covered by solid electrolyte interphase (SEI) and interspersed with nanopores (sub-10 nm to 100 nm scale). Lage cracks and voids are also a key feature. On potassiophilic support, the deposit is dense and pore-free, with uniform surface and SEI morphology. Mesoscale modeling captures the critical role of substrate-metal interaction on K metal film nucleation and growth, as well as the associated stress state.     

Hydrogenation of Epoxides to Anti-Markovnikov Alcohols over a Nickel Heterogenous Catalyst Prepared from Biomass (Rice) Waste

The synthesis of primary alcohols (from olefins) is an important and challenging transformation, as most of the current methods suffer from regioselectivity issues. This work describes the utilization of rice husk (RH) from agricultural waste as support for the preparation of a catalyst for the conversion of olefin oxides to primary alcohols. The catalyst was synthesized by pyrolysis of RH impregnated with nickel, and characterized by IR, AAS, XRD, BET, XPS, TEM, and TPD technics. The catalyst shows excellent activity and selectivity towards anti-Markovnikov alcohols, acting simultaneously as Brønsted acid, solid Lewis acid, and as hydrogenation catalyst. A substrate screening was done, the catalyst's recycling stability was assessed, and a plausibly reaction mechanism was proposed.     

Quantitative Nanoscale Secondary Ion Mass Spectrometry (NanoSIMS) Imaging of Individual Vesicles to Investigate the Relation between Fraction of Chemical Release and Vesicle Size

We used correlative transmission electron microscopy (TEM) and nanoscale secondary ion mass spectrometry (NanoSIMS) imaging to quantify the contents of subvesicular compartments, and to measure the partial release fraction of ¹³C-dopamine in cellular nanovesicles as a function of size. Three modes of exocytosis comprise full release, kiss-and-run, and partial release. The latter has been subject to scientific debate, despite a growing amount of supporting literature. We tailored culturing procedures to alter vesicle size and definitively show no size correlation with the fraction of partial release. In NanoSIMS images, vesicle content was indicated by the presence of isotopic dopamine, while vesicles which underwent partial release were identified by the presence of an ¹²⁷I-labelled drug, to which they were exposed during exocytosis allowing entry into the open vesicle prior to its closing again. Demonstration of similar partial release fractions indicates that this mode of exocytosis is predominant across a wide range of vesicle sizes.     

Metal-Organic Framework Thin Films as Ideal Matrices for Azide Photolysis in Vacuum

Studies on reactions in solutions are often hampered by solvent effects. In addition, detailed investigation on kinetics is limited to the small temperature regime where the solvent is liquid. Here, we report the in situ spectroscopic observation of UV-induced photochemical reactions of aryl azides within a crystalline matrix in vacuum. The matrices are formed by attaching the reactive moieties to ditopic linkers, which are then assembled to yield metal–organic frameworks (MOFs) and surface-mounted MOFs (SURMOFs). These porous, crystalline frameworks are then used as model systems to study azide-related chemical processes under ultrahigh vacuum (UHV) conditions, where solvent effects can be safely excluded and in a large temperature regime. Infrared reflection absorption spectroscopy (IRRAS) allowed us to monitor the photoreaction of azide in SURMOFs precisely. The in situ IRRAS data, in conjunction with XRD, MS, and XPS, reveal that illumination with UV light first leads to forming a nitrene intermediate. In the second step, an intramolecular rearrangement occurs, yielding an indoloindole derivative. These findings unveil a novel pathway for precisely studying azide-related chemical transformations. Reference experiments carried out for solvent-loaded SURMOFs reveal a huge diversity of other reaction schemes, thus highlighting the need for model systems studied under UHV conditions.     

Pushing the Upper Limit of Nucleophilicity Scales by Mesoionic N-Heterocyclic Olefins

A series of mesoionic, 1,2,3-triazole-derived N-heterocyclic olefins (mNHOs), which have an extraordinarily electron-rich exocyclic CC-double bond, was synthesized and spectroscopically characterized, in selected cases by X-ray crystallography. The kinetics of their reactions with arylidene malonates, ArCH=C(CO₂Et)₂, which gave zwitterionic adducts, were investigated photometrically in THF at 20 °C. The resulting second-order rate constants k₂(20 °C) correlate linearly with the reported electrophilicity parameters E of the arylidene malonates (reference electrophiles), thus providing the nucleophile-specific N and s_N parameters of the mNHOs according to the correlation lg k₂(20 °C)=s_N(N+E). With 21<N<32, the mNHOs are much stronger nucleophiles than conventional NHOs. Some mNHOs even excel the reactivity of mono- and diacceptor-substituted carbanions. It is exemplarily shown that the reactivity parameters thus obtained allow to calculate the rate constants for mNHO reactions with further Michael acceptors and predict the scope of reactions with other electrophilic reaction partners including carbon dioxide, which gives zwitterionic mNHO-carboxylates. The nucleophilicity parameters N correlate linearly with a linear combination of the quantum-chemically calculated methyl cation affinities and buried volumes of mNHOs, which offers a valuable tool to tailor the reactivities of strong carbon nucleophiles.     

N=8 Armchair Graphene Nanoribbons: Solution Synthesis and High Charge Carrier Mobility**

Structurally defined graphene nanoribbons (GNRs) have emerged as promising candidates for nanoelectronic devices. Low band gap (<1 eV) GNRs are particularly important when considering the Schottky barrier in device performance. Here, we demonstrate the first solution synthesis of 8-AGNRs through a carefully designed arylated polynaphthalene precursor. The efficiency of the oxidative cyclodehydrogenation of the tailor-made polymer precursor into 8-AGNRs was validated by FT-IR, Raman, and UV/Vis-near-infrared (NIR) absorption spectroscopy, and further supported by the synthesis of naphtho[1,2,3,4-ghi]perylene derivatives ( 1 and 2 ) as subunits of 8-AGNR , with a width of 0.86 nm as suggested by the X-ray single crystal analysis. Low-temperature scanning tunneling microscopy (STM) and solid-state NMR analyses provided further structural support for 8-AGNR . The resulting 8-AGNR exhibited a remarkable NIR absorption extending up to ∼2400 nm, corresponding to an optical band gap as low as ∼0.52 eV. Moreover, optical-pump TeraHertz-probe spectroscopy revealed charge-carrier mobility in the dc limit of ∼270 cm² V⁻¹ s⁻¹ for the 8-AGNR .     

On-Surface Synthesis and Real-Space Visualization of Aromatic P3N3

On-surface synthesis is at the verge of emerging as the method of choice for the generation and visualization of unstable or unconventional molecules, which could not be obtained via traditional synthetic methods. A case in point is the on-surface synthesis of the structurally elusive cyclotriphosphazene (P₃N₃), an inorganic aromatic analogue of benzene. Here, we report the preparation of this fleetingly existing species on Cu(111) and Au(111) surfaces at 5.2 K through molecular manipulation with unprecedented precision, i.e., voltage pulse-induced sextuple dechlorination of an ultra-small (about 6 Å) hexachlorophosphazene P₃N₃Cl₆ precursor by the tip of a scanning probe microscope. Real-space atomic-level imaging of cyclotriphosphazene reveals its planar D_3h-symmetric ring structure. Furthermore, this demasking strategy has been expanded to generate cyclotriphosphazene from a hexaazide precursor P₃N₂₁ via a different stimulation method (photolysis) for complementary measurements by matrix isolation infrared and ultraviolet spectroscopy.     

Azodicarboxylate-Mediated Peptide Cyclisation: Application to Disulfide Bond Formation in Solution and Solid Phase

Cyclic peptides are important molecules, playing key roles in protein architecture, as chemical probes, and increasingly as crucial structural elements of clinically-useful therapeutics. Herein we report methodology using azodicarboxylates as efficient reagents for the facile synthesis of cyclic peptides through a disulfide bridge. The utility of this approach in both solution and solid-phase, and compatibility with common amino acid side chain functionalities is demonstrated, resulting in cyclic peptides in good yield and purity. This approach has significant potential application for synthesis of molecules of biological or therapeutic significance.