In situ tissue pathology from spatially encoded mass spectrometry classifiers visualized in real time through augmented reality

Integration between a hand-held mass spectrometry desorption probe based on picosecond infrared laser technology (PIRL-MS) and an optical surgical tracking system demonstrates in situ tissue pathology from point-sampled mass spectrometry data. Spatially encoded pathology classifications are displayed at the site of laser sampling as color-coded pixels in an augmented reality video feed of the surgical field of view. This is enabled by two-way communication between surgical navigation and mass spectrometry data analysis platforms through a custom-built interface. Performance of the system was evaluated using murine models of human cancers sampled in situ in the presence of body fluids with a technical pixel error of 1.0 ± 0.2 mm, suggesting a 84% or 92% (excluding one outlier) cancer type classification rate across different molecular models that distinguish cell-lines of each class of breast, brain, head and neck murine models. Further, through end-point immunohistochemical staining for DNA damage, cell death and neuronal viability, spatially encoded PIRL-MS sampling is shown to produce classifiable mass spectral data from living murine brain tissue, with levels of neuronal damage that are comparable to those induced by a surgical scalpel. This highlights the potential of spatially encoded PIRL-MS analysis for in vivo use during neurosurgical applications of cancer type determination or point-sampling in vivo tissue during tumor bed examination to assess cancer removal. The interface developed herein for the analysis and the display of spatially encoded PIRL-MS data can be adapted to other hand-held mass spectrometry analysis probes currently available.

Integration between a hand-held mass spectrometry desorption probe based on picosecond infrared laser technology (PIRL-MS) and an optical surgical tracking system demonstrates in situ tissue pathology from point-sampled mass spectrometry data.     

A comparative multi-reference configuration interaction study of the low-lying states of two thione isomers of thiophenol

Multi-reference configuration interaction, MR-CI (including extensivity corrections, named +Q), calculations were performed on the S₀–S₃ states of cyclohexa-2,4-diene-1-thione (thione 24 ) and cyclohexa-2,5-diene-1-thione (thione 25 ), which are thione isomers of thiophenol. Several types of uncontracted MR-CIS and MR-CISD wavefunctions were employed, comprising MR-CI expansions as large as ~365 × 10⁶ configuration state functions. The nature of the studied excited states was characterized. Vertical excitation energies (ΔE) and oscillator strengths (f) were computed. The most intense transitions (S₀ → S₂ for 24 and S₀ → S₃ for 25 ) did not change with the wavefunction, although a variation as large as ~1 eV was obtained for the S₃ state of 24 , at the highest (MR-CI+Q) level. On the other hand, ΔE changed at most by ~0.56 eV for 25 as the wavefunction changes, at the same level. The S₁ state of both thiones was found to have nπ* character and is in the visible region. For 24 , S₂ and S₃ are ππ* and nπ* states, respectively, while for 25 the reverse order is obtained. S₂ and S₃ are in the range ~3.5 to 5.2 eV, again at the highest level. It is the first time that the excited states of the title molecules are studied. The computed results agree with the experimental onset of photoreactions of thiones 24 and 25 found by Reva et al (Phys. Chem. Chem. Phys., 2015 , 17, 4888).     

The solvent effect in obtaining of acid–base multicomponent systems: thermal,structural and luminescence study

Journal of Thermal Analysis and Calorimetry - Acid–base multicomponent systems based on active pharmaceutical ingredients 2-chloro-5-nitrobenzoic acid (2Cl5NBH) and monoethanolamine were...     

Solvent-free,microwave-assisted synthesis of thiophene oligomers via Suzuki coupling

The purpose of this study was to obtain a rapid, efficient, and environmentally friendly methodology for the synthesis of highly pure thiophene oligomers. The solvent-free, microwave-assisted coupling of thienyl boronic acids and esters with thienyl bromides, using aluminum oxide as the solid support, allowed us to rapidly check the reaction trends on changing times, temperature, catalyst, and base and easily optimize the experimental conditions to obtain the targeted product in fair amounts. This procedure offers a novel, general, and very rapid route to the preparation of soluble thiophene oligomers. Thus, for example, quaterthiophene was obtained in 6 min by reaction of 2-bromo-2,2'-bithiophene with bis(pinacolato)diboron (isolated yield 65%), whereas quinquethiophene was obtained in 11 min by reaction of dibromoterthiophene with thienylboronic acid (isolated yield 74%). The synthesis of new chiral 2,2'-bithiophenes is reported. The detailed analysis of the byproducts of some reactions allowed us to elucidate a few aspects of reaction mechanisms. While the use of microwaves proved to be very convenient for the coupling between conventional thienyl moieties, the same was not true for the coupling of thienyl rings to thienyl-S,S-dioxide moieties. Indeed, in this case, the targeted product was obtained in low yields because of the competitive, accelerated, Diels-Alder reaction that affords a variety of condensation products.     

The speciation of rhodium(III) in hydrochloric acid media by capillary zone electrophoresis

A fast and effective method to study the aquation of rhodium(III) chlorocomplex in hydrochloric solutions using capillary zone electrophoresis (CZE) is developed. At least five species, some of which seem to be oligomeric, are formed in solution during the aquation process at pH>1. The fast hydration of RhCl₆³⁻ makes this species impossible to detect. The first species detected in the optimised conditions is RhCl₅(H₂O)²⁻ although RhCl₄(H₂O)₂⁻ is the main species during the first stage of the aquation process. When equilibrium is reached either RhCl₃(H₂O)₃ or a cationic complex, RhCl₂(H₂O)₄⁺, is formed as the main species. Matrix Assisted Laser Desorption Ionisation Time of Flight Mass Spectrometry (MALDI-TOF MS) is used as a novel technique to elucidate the structure of the rhodium aqua/chloro complexes formed in solution. Results obtained by CZE are confirmed by spectrophotometry.     

Regiocontrolled synthesis of enantiopure 3,3'-thiosubstituted biphenyls

Sulfenylation of 6,6'-dimethoxy-2,2'-dihydroxybiphenyl, used as a racemic mixture and single enantiomers, by phthalimidesulfenyl chloride afforded the corresponding 3,3'-N,N'-dithiophthalimide with complete regioselectivity. Simple manipulations of the latter compound allowed access to the corresponding bis-thiol or o-thioquinone as useful intermediates for the synthesis of new sulfur-containing open-chain and macrocyclic C(2) enantiopure ligands. The application of this methodology to the preparation of a biphenyl bearing two cysteine units as potential HIV-1 protease inhibitor is also described.     

Diketopyrrolopyrrole‐Porphyrin Conjugates with High Two‐Photon Absorption and Singlet Oxygen Generation for Two‐Photon Photodynamic Therapy

Two‐photon photodynamic therapy is a promising therapeutic method which requires the development of sensitizers with efficient two‐photon absorption and singlet‐oxygen generation. Reported here are two new diketopyrrolopyrrole‐porphyrin conjugates as robust two‐photon absorbing dyes with high two‐photon absorption cross‐sections within the therapeutic window. Furthermore, for the first time the singlet‐oxygen generation efficiency of diketopyrrolopyrrole‐containing systems is investigated. A preliminary study on cell culture showed efficient two‐photon induced phototoxicity.     

Electrocatalytic Carbon Dioxide Reduction by Using Cationic Pentamethylcyclopentadienyl–Iridium Complexes with Unsymmetrically Substituted Bipyridine Ligands

Eight [Ir(bpy)Cp*Cl]⁺‐type complexes (bpy= bipyridine, Cp*=1,2,3,4,5‐pentamethylcyclopentadienyl) containing differently substituted bipyridine ligands were synthesized and characterized. Cyclic voltammetry (CV) of the complexes in Ar‐saturated acetonitrile solutions showed that the redox behavior of the complexes could be fine tuned by the electronic properties of the substituted bipyridine ligands. Further CV in CO₂‐saturated MeCN/H₂O (9:1, v/v) solutions showed catalytic currents for CO₂ reduction. In controlled potential electrolysis experiments (MeCN/MeOH (1:1, v/v), E_app=?1.80 V vs Ag/AgCl), all of the complexes showed moderate activity in the electrocatalytic reduction of CO₂ with good stability over at least 15 hours. This electrocatalytic process was selective toward formic acid, with only traces of dihydrogen or carbon monoxide and occasionally formaldehyde as byproducts. However, the turnover frequencies and current efficiencies were quite low. No direct correlation between the redox potentials of the complexes and their catalytic activity was observed.