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.     

Dewetting of unreacted epoxy/amine mixtures on silica

We employ a direct method, time-of-flight secondary ion mass spectroscopy (ToF-SIMS), to determine experimentally the chemical compositions of the wetted and dewetted regions of an uncured epoxy thin film. Determining the composition of the dewetted region indicated the presence of a very thin sublayer of resin in what was thought to be a region devoid of resin. The capability of ToF-SIMS to probe small 65 x 65 microm(2) areas of the surface has permitted us to directly compare the SIMS spectra of the wetted and dewetted regions to the survey spectra of the reactants. This may indicate the strength of resin/silica interactions, which determine interface formation and properties.     

Hyperaromatic stabilization of arenium ions

Benzene-cis- and trans-1,2-dihydrodiols undergo acid-catalyzed dehydration at remarkably different rates: k(cis)/k(trans) = 4500. This is explained by formation of a β-hydroxycarbocation intermediate in different initial conformations, one of which is stabilized by hyperconjugation amplified by an aromatic no-bond resonance structure (HOC(6)H(6)(+) ? HOC(6)H(5) H(+)). MP2 calculations and an unfavorable effect of benzoannelation on benzenium ion stability, implied by pK(R) measurements of -2.3, -8.0, and -11.9 for benzenium, 1-naphthalenium, and 9-phenanthrenium ions, respectively, support the explanation.     

Hyperaromatic stabilization of arenium ions: a remarkable cis stereoselectivity of nucleophilic trapping of β-hydroxyarenium ions by water

Cis- and trans-1,2-dihydrodiol isomers of benzene undergo acid-catalyzed dehydration to form phenol. In principle the isomeric substrates react through a common β-hydroxybenzenium (cyclohexadienyl) carbocation. Notwithstanding, the isomers show a large difference in reactivity, k(cis)/k(trans) = 4500. This difference is reduced to k(cis)/k(trans) = 440 and 50 for the 1,2-dihydrodiols of naphthalene and 9,10-dihydrodiols of phenanthrene, respectively, and to 6.9 for the dihydrodiols of the nonaromatic 7,8-double bond of acenaphthylene. Because the difference in stabilities of cis- and trans-dihydrodiols should be no more than 2-3-fold, these results imply a high cis stereoselectivity for nucleophilic trapping of a β-hydroxyarenium cation by water in the reverse of the carbocation-forming reaction. This is confirmed by studies of the 10-hydroxy-9-phenanthrenium ion generated from aqueous solvolyses of the trans-9,10-bromohydrin derivative of phenanthrene and the monotrichloroacetate ester of the phenanthrene cis-9,10-dihydrodiol. The cis stereoselectivity of forward and reverse reactions is explained by the formation (in the "forward" reaction) of different conformations of carbocation from cis- and trans-dihydrodiol reactants with respectively β-C-H and β-C-OH bonds in pseudoaxial positions with respect to the charge center of the carbocation optimal for hyperconjugation. Formation of different conformations is constrained by departure of the (protonated) OH leaving group from a pseudoaxial position. The difference in stability of the carbocations is suggested to stem (a) from the greater hyperconjugative ability of a C-H than a C-OH bond and (b) from enhanced conjugation arising from the stabilizing influence of an aromatic ring in the no-bond resonance structures representing the hyperconjugation (C(6)H(6)OH(+) ? C(6)H(5)OH H(+)). This is consistent with an earlier suggestion by Mulliken and a demonstration by Schleyer that the benzenium ion is subject to hyperconjugative aromatic stabilization. It is proposed that, in analogy with the terms homoconjugation and homoaromaticity, arenium ions should be considered as "hyperaromatic".     

Extraction of chromium-DCTA complex with trioctylmonomethylammonium chloride (Aliquat-336)

The violet complex formed between chromium(III) DCTA can be quantitatively extracted by Aliquat-336 in chloroform as [Cr(DCTA)] [Aliquat-336]. The conditions for quantitative extraction have been established. The method facilitates the determination of chromium in the presence of other coloured cations.     

Periodic nanostructures on Si(100) surfaces generated by high-repetition rate sub-15 fs pulsed near-infrared laser light

Nanoscale rifts and ripples at a periodicity of 130 nm were generated on Si(100) surfaces immersed in water using tightly focused 800 nm 12 fs pulsed 85 MHz laser light at subnanojoule pulse energies. At radiant exposure close to the ablation threshold rifts were typically 20-50 nm in width and 70 nm in depth running perpendicular to the laser polarization. On increase of the irradiance, the rifts broadened and formed periodic ripples, whereas at highest exposure, a random nanoporous surface topology emerged. Rift and ripple formation is explained by laser-induced standing surface plasma waves, which result in periodic variation of dissipation and ablation.     

Chemical Composition of Pentanema kurdistanicum Essential Oil

Chemistry of Natural Compounds -     

Molecular Modeling of Human CCR2 Receptor within POPC Lipid Bilayer

Structural Chemistry - Chemokine receptor 2 (CCR2), a G-protein coupled receptor (GPCR), is a critical target for several inflammatory and autoimmune diseases. The main restriction on designing...     

Hyperaromatic stabilization of arenium ions: acid-catalyzed dehydration of 2-substituted 1,2-dihydro-1-naphthols

Rate constants for acid-catalyzed dehydration of cis-2-substituted 1,2-dihydro-naphthols are well correlated by the Taft relationship log k = -0.49 - 8.8σ(I), with minor negative deviations for OH and OMe. By contrast the trans substituents show a poor correlation with σ(I) and in most cases react more slowly than their cis isomers. The behavior is consistent with rate-determining formation of a 2-substituted carbocation (naphthalenium ion) intermediate that for cis reactants possesses a 2-C-H bond suitably oriented for hyperconjugation with the charge center. For the trans isomers the 2-substituent itself is oriented for hyperconjugation in the initially formed conformation of the cation. It is argued that k(cis)/k(trans) rate ratios for substituents (Me, 8.4; Bu(t), 12.7; Ph, 3.8; NH(3)(+), 160; OH, 440) reflect their hyperconjugating ability relative to hydrogen. Faster reactions of trans isomers are observed for substitutents known (RS, N(3)) or suspected (EtSO, EtSO(2)) of stabilizing the cation by a π or σ neighboring group effect. The good Taft correlation is taken to indicate that cis substuents are reacting normally, differentiated only by their inductive effects. The slower reactions of the trans isomers are the judged to be "abnormal". This is confirmed by comparing effects of cis and trans β-OH substituents on the reactivities of dihydro phenols, naphthols, and phenanthrols. Whereas k(H)/k(OH) for cis substituents varies by less than 8-fold and is consistent with the influence of an inductive effect of the OH group (k(H)/k(OH) ≈ 2000), k(H)/k(OH) for the trans substituents varies by 3 orders of magnitude, reflecting the additional influence of the lesser hyperconjugating ability of a C-OH bond compared to a C-H bond. The magnitude and variation of this difference is consistent with C-H hyperconjugation conferring aromatic character on the arenium ions.     

Submicron-dot chains at and beneath surfaces of glasses written by a picojoule 12-fs laser scanning microscope

A near-infrared 12-fs laser scanning microscope was employed for structuring glass surfaces. A Ti–sapphire laser operated at 85 MHz and emitted light pulses at wavelengths around 800 nm. A focused laser beam with a mean power of less than 27 mW, corresponding to a maximal pulse energy of 318 pJ, was applied for line scanning at and beneath the surfaces of cover slips as well as of a filter glass BG39. Periodic arrangements of dots along the processed lines were produced through digital control of the scanner. Depending on the pulse energy and the scan speed, the diameter of the dots ranged from 550 nm down to 100 nm. For the cover slips, the dots occur as cavities after wet chemical etching. For BG39, which exhibits strong near-infrared absorption, both chains of cavities and bumps can be generated without any etching process. The result shows that structures with a size down to 1/8λ can be generated, probably through nonlinear single-photon processes confined within the focal volume.