Small Molecular Species Research Articles

Construction of a multi-signal near-infrared fluorescent probe for sensing of hypochlorite concentration fluctuation in living animals

Hypochlorite (HClO/ClO−) is highly oxidizing and plays important roles in the immune system of living organisms. Up- or down-regulation of HClO/ClO− concentrations may induce many diseases. However, it remains a big challenge to track HClO/ClO− concentration fluctuation in situ because of its low content and high reactivity. Herein, we present the rational design of a powerful ratiometric fluorescent probe (Cy7-Nil) for measuring HClO/ClO− concentrations for the first time. The advantageous features of Cy7-Nil include the composition of two near-infrared chromophores, possessing three emission signals (560 nm, 650 nm and 780 nm), HClO/ClO− concentration dependent fluorescence, and two-photon excitation property. These superior features of Cy7-Nil enable the ratiometric detection of HClO/ClO− concentration range in dual ratiometric channels (I650 / I560 and I650 / I780) and ratiometric detection of endogenous HClO/ClO− concentrations in living animals for the first time. This work provides a universal approach to fabricate novel ratiometric probes for monitoring levels of reactive small molecular species in living animals.

Detection of small DNA fragments by biolayer interferometry

Small molecular weight species such as miRNAs and other nucleic acid fragments are gaining an increased interest as biomarkers for relevant diseases. Also, cheap and rapid assays for their routine detection are becoming an urgent need. We have investigated the usability and convenience of a price affordable, label free and fast technique for their detection on a laboratory scale small device based on Bio-Layer Interferometry. Using a model DNA fragment (7 kDa), we have found that the technique is effectively fast and sensitive enough for the detection of nucleic acid fragments having a MW below the stated molecular size detection limit (10 kDa). The test molecule has been detected in solution at 100 nM in a direct capture experiment and up to about 10 nM following an improved approach where an enhancing probe is used to increase the apparent molecular dimensions of the analyte. The technique, following further optimizations, can be applied for the routine, cheap and fast analysis of small nucleic acid fragments that have a relevance in diagnosis and in therapy.

Application of molecular SERS nanosensors: where we stand and where we are headed towards?

Molecular specific and highly sensitive detection is the driving force of the surface-enhanced Raman spectroscopy (SERS) community. The technique opens the window to the undisturbed monitoring of cellular processes in situ or to the quantification of small molecular species that do not deliver Raman signals. The smart design of molecular SERS nanosensors makes it possible to indirectly but specifically detect, e.g. reactive oxygen species, carbon monoxide or potentially toxic metal ions. Detection schemes evolved over the years from simple metallic colloidal nanoparticles functionalized with sensing molecules that show uncontrolled aggregation to complex nanostructures with magnetic properties making the analysis of complex environmental samples possible. The present article gives the readership an overview of the present research advancements in the field of molecular SERS sensors, highlighting future trends.

Polycyclic aromatic hydrocarbon formation chemistry in a plasma jet revealed by IR-UV action spectroscopy

Large polycyclic aromatic hydrocarbons (PAHs) are the most abundant complex molecules in the interstellar medium; however, their possible formation pathways from small molecular species are still elusive. In the present work, we follow and characterize the formation of PAHs in an electrical discharge, specifically the PAH naphthalene in a molecular beam of argon. The fragments, products and reaction intermediates are unambiguously structurally identified by mass-selective IR-UV spectroscopy combined with quantum chemical calculations. This experiment provides evidence of the formation of larger PAHs containing up to four cyclic rings in the gas phase originating from a non-radical PAH molecule as a precursor. In addition to PAH formation, key resonance stabilized radical intermediates and intermediates containing di-acetylenic side groups are unambiguously identified in our experiment. We thereby not only reveal competing formation pathways to larger PAHs, but also identify intermediate species to PAH formation that are candidates for detection in radio-astronomy.

First-principles investigation of CO and CO2 adsorption on [formula omitted]-Al2O3 supported monoatomic and diatomic Pt clusters

Supported clusters of transition metal atoms are key components of heterogeneous catalysts. Understanding their interaction with small molecular species is therefore an important step in catalyst design. In this work, we provide a detailed first-principles investigation of the adsorption properties of CO and CO2 on Ptn(n=1,2) clusters supported by a γ-Al2O3 (1 0 0) substrate. In particular, important parameters such as the stability of the Pt clusters, molecular adsorption energies and vibration frequencies were investigated. All Pt2 clusters exhibit lower adsorption energies than their monoatomic counterparts, especially single Pt atoms embedded in the surface of the support. Atomically preadsorbed Pt acts as an anchor for the CO molecule, increasing its adsorption energy compared to the bare surface. The support actively participates in stabilizing the adsorbates and a markedly different behaviour can be expected depending on the adsorption site being on the surface of small Pt clusters or on the Pt/support interface. Vibrational frequencies of CO and CO2 adsorbed on the supported clusters can be used to gain insight into the degree of dispersion of the metallic component of the catalyst, and can be profitably used in the design of novel single-atom catalysts (SACs).

Moment Dynamics of Zirconia Particle Formation for Optimizing Particle Size Distribution.

We study the particle formation process of Zirconia ()-based material. With a model-based description of the particle formation process we aim for identifying the main growth mechanisms for different process parameters. After the introduction of a population balance based mathematical model, we derive the moment dynamics of the particle size distribution and compare the model to experimental data. From the fitted model we conclude that growth by molecular addition of Zr-tetramers or Zr-oligomers to growing particles as well as size-independent particle agglomeration takes place. For the purpose of depositing zirconia-based material (ZrbM) on a substrate, we determine the optimal process parameters such that the mineralization solution contains preferably a large number of nanoscaled particles leading to a fast and effective deposition on the substrate. Besides the deposition of homogeneous films, this also enables mineralization of nanostructured templates in a bioinspired mineralization process. The developed model is also transferable to other mineralization systems where particle growth occurs through addition of small molecular species or particle agglomeration. This offers the possibility for a fast determination of process parameters leading to an efficient film formation without carrying out extensive experimental investigations.

Spectrophotometric determination of choline in pharmaceutical formulations via host-guest complexation with a biomimetic calixarene receptor

Choline is a quaternary ammonium bioactive compound that is used as a dietary supplement. Direct determination of choline in pharmaceutical formulations is a challenging analytical task. The strong UV absorbance of p-sulfonatocalix[4]arene (SC4) and its outstanding complexation properties towards quaternary ammonium compounds have been utilized to develop a method to detect and quantify choline in aqueous solution. This method has been applied to a commercial pharmaceutical choline formulation showing results with no statistically significant difference from those obtained by the official U.S. Pharmacopeial method. The method was validated according to ICH guidelines and the limit of detection for choline was calculated to be 7.2 × 10−6 mol L−1 (1.30 μg mL−1). The host-guest complexation between SC4 and choline were investigated using UV and 1H NMR spectroscopy and DFT calculations. The peak amplitude of the host-guest complexes formed were found to be linearly proportional to the concentration of the choline and l-carnitine analytes in the ranges of 1.0 × 10−5 to 1.6 × 10−4 mol L−1 and 1.0 × 10−5 to 1.8 × 10−4 mol L−1 respectively. The reaction stoichiometry between either choline or l-carnitine with SC4 in the formed complexes were determined to be 1:1 while the stability constants for the complexes formed were estimated to be 8.3 × 104 M−1 and 2.8 × 104 M−1 in the case of choline and l-carnitine, respectively. Both 1H NMR spectroscopy and DFT calculations suggest the complexation between choline and SC4 involves the insertion of the trimethylammonium group of choline into the cavity of SC4 in agreement with previously published X-ray data. The spectrophotometric method presented here should not be limited to the determination of choline. The linear relationship between the peak amplitude of the host-guest complex formed between SC4 and l-carnitine presented here suggests the applicability of the method for the detection of other small molecular species possessing a quaternary ammonium group.

Research Gate (RG) is a Meeting Point for Progress in Chemical Knowledge

Chemistry is one of the eldest and basic sciences. The technological progress is depending on progress in chemistry. Without evaluation of nature and preparation of a pure substance, it is not imaginable existence of modern biology, medicine, metallurgy and physics. All kind of existing technologies needs distinct in nature and pure in quality substances for existence and further progress. RG aims to bring together leading academic scientists, researchers and research scholars to exchange and share their experiences and research results on all aspects of chemistry and related fields. It also provides an interdisciplinary platform for researchers, practitioners and educators to present and discuss the most recent innovations, trends, and concerns as well as practical challenges encountered, and solutions adopted in the fields of chemistry. One of the nearly developed concepts in liquid chromatography is described in [1], which is a new type of liquid chromatography, the new technology as the Colloidal High-Performance Liquid Chromatography (CHPLC). This type of new technological approach in high-performance liquid chromatography is a simple time- and labor-saving one-step procedure suitable for analytical-, semipreparative-, and preparative-scale preparation of bacteriocins and other cationic antibacterial peptides as well as other cationic small molecular weight species. It allows to suspensions of bacterial cells, other colloidal and fast-particle materials, and dissolved anionic molecules passed through the column; however, cationic bacteriocins, small cationic peptides, organic cationic molecules and metal cations were separated by chromatography. The purity of the target substance generally at more than 95% was achieved by the judgment of spectral, chromatographic, and antimicrobial activity. In [1] was described the preparation, purification and chromatography of bacteriocin, bacitracin and lysozyme. It is my pleasure to invite all the great scientists, academicians, young researchers, students and everyone who is interested in Science, especially in chemistry from all over the world to attend the RG. All who are interested in theoretical and applicational aspects in Chemistry, New Materials Research and Nanotechnology will find them in RG. The topics as: Organic Chemistry and Advances in Organic Chemistry, Analytical Chemistry, Medicinal Chemistry, Clinical Chemistry, Forensic Chemistry, Industrial Chemistry and Occupational Chemistry, Food Chemistry, Green Chemistry and Chemical Renewable Resources, Agricultural and Food Chemistry, Physical and Theoretical Chemistry, Biological Chemistry, Marine Chemistry, Inorganic Chemistry, Environmental Chemistry, Nanoscience and Technology, Polymer Chemistry, Material Chemistry, Natural Resources Chemistry and Natural Products Chemistry, Electrochemistry, Geochemistry, Radio and Nuclear chemistry, Physical Chemistry, Theoretical Chemistry, Space (Interplanetary) Chemistry and many more are present on the pages of RG. At RG you will find the state-of-the-art research and cutting-edge theoretical and applicational technologies. The RG is covering a number of global aspects in Chemistry, New Materials Science and Nanotechnology from purely fundamental research up to practical applications.

Cobalt based functional inorganic materials: Electrocatalytic water oxidation

Water splitting is considered to be one of the most promising sources of sustainable energy, as it can produce hydrogen ( $$\hbox {H}_{2}$$ ) fuel. To have successful water splitting in a sustained manner, it is necessary to develop efficient and robust catalysts that can perform water oxidation, the bottleneck process of water splitting either electrochemically or photochemically. Here, we have presented a brief descriptive analysis of different aspects of designing such catalysts in connection with our recent works on the same field. The focus of the article is to discuss contemporary works in the field of designing cobalt-based heterogeneous water oxidation electrocatalysts. To the best of our knowledge, although cobalt is the most extensively studied 1st row transition metal for water oxidation catalysis reaction, no such report has been found where the simplest cobalt complex, [ $$\hbox {Co(H}_{2}\hbox {O})_{6}]^{2+}$$ , has been employed as a water oxidation catalyst. Not only that, reports of cobalt-based simple and small molecular catalysts are also not very frequent. With the help of our recent works, we have tried to detail here a wide aspect of the study on cobalt-based simple and small molecular catalysts, starting from the reasons behind the scarcity of such water oxidation catalysts, to development of new ideas addressing the challenges in utilization of such small cobalt complexes for water oxidation catalyst. Here, we have addressed the scope of encapsulation chemistry in designing robust and efficient heterogeneous water oxidation catalysts using cobalt-based small molecular guest species. With the help of structural insight, gained from the recent results, we published in the field of water oxidation catalysis; here, we try to formulate a general approach that can help to prepare water oxidation catalyst based on host-guest chemistry. The article critically evaluates our recent results in connection with the approach of addressing the problem. SYNOPSIS An efficient electrocatalytic water oxidation can be achieved by cobalt(II)-based functional materials that comprise of a mononuclear Co(II)-aqua coordination complex [ $$\hbox {Co}(\hbox {H}_{2}\hbox {O})_{4}\hbox {(DMF)}_{2}]^{2+}$$ , included in the confined space of a metal organic framework (MOF) material, zeolite-Y-supported $$\upalpha $$ - $$\hbox {Co(OH)}_{2}$$ nano-film and ZIF-8 MOF-encapsulated cobalt(II)-centred Keggin-type polyoxometalate. The relevant kinetic analyses have been discussed in details.

Mild degradation of Powder River Basin sub-bituminous coal in environmentally benign supercritical CO2-ethanol system to produce valuable high-yield liquid tar

A novel and environmentally benign binary supercritical fluid system, comprised of supercritical CO2 and ethanol (SCCO2-ethanol), was employed to convert coal, a conventional energy resource, into high-value liquid tar which can be used as feedstock for the production of fuels/chemicals and carbon fibers. The SCCO2-ethanol system shows good performance for producing valuable liquid tar in high yield from Powder River Basin sub-bituminous coal. The results show that the highest yield of liquid tar reaches up to approximate 38 wt% (38 g/100 g raw coal) at 350 °C, and that SCCO2 can promote the liquid tar yield by 5.6 wt% compared to that using pure ethanol due to the synergistic effect between ethanol and SCCO2. The liquid tars are better candidates as clean fuels than the raw coal or even bituminous coal due to their higher heating values and almost free from ash. The liquid tars from degradation in SCCO2-ethanol (liquid tarSCCO2-ethanol) and in ethanol without SCCO2 (liquid tarethanol) at 350 °C were characterized with multiple analytical techniques. Fourier transform infrared analyses indicated that both liquid tars have similar distributions of functional groups. The proportion of volatile and small-molecular species in liquid tarSCCO2-ethanol is higher than liquid tarethanol according to thermogravimetric analysis. Further, gas chromatograph/mass spectrometry analyses show that phenols and aliphatic esters are the dominant volatile compounds in both liquid tars. The 1H and 13C nuclear magnetic resonance analyses reveal that both liquid tars have low aromaticity and liquid tarSCCO2-ethanol contains more aromatic carbons than liquid tarethanol, especially highly condensed aromatic carbons. Methylene and aliphatic and aromatic CH3 are the major aliphatic moieties in both liquid tars. The liquid tars can be separated into light oil and asphaltene fractions by extraction with n-heptane. In addition, the asphaltene fraction has potential to be used as the precursor for fabricating carbon nanofibers via electrospinning. Possible mechanisms for releasing volatile compounds and asphaltene from Powder River Basin sub-bituminous coal by SCCO2-ethanol degradation were also discussed.

A simple pyrene-based fluorescent probe for highly selective detection of formaldehyde and its application in live-cell imaging

A novel and simple pyrene-based fluorescent probe (B1) was synthesized and used for the detection of formaldehyde (FA). When B1 was added to FA in CH3CH2OH/HEPES (10 mM, pH = 7.4, 1:99, v/v) solution, the solution system strongly enhanced the fluorescence. Over various small molecular species, probe B1 showed high sensitivity and selectivity for detecting FA, with a low limit of detection (0.107 μM). Furthermore, probe B1 was successfully applied for visualizing FA in human embryonic kidney (HEK293T) cells, demonstrating its value of application in living biomedical samples.

Infrared spectra of complex organic molecules in astronomically relevant ice matrices

Context. The number of identified complex organic molecules (COMs) in inter- and circumstellar gas-phase environments is steadily increasing. Recent laboratory studies show that many such species form on icy dust grains. At present only smaller molecular species have been directly identified in space in the solid state. Accurate spectroscopic laboratory data of frozen COMs, embedded in ice matrices containing ingredients related to their formation scheme, are still largely lacking.Aim. This work provides infrared reference spectra of acetaldehyde (CH3CHO), ethanol (CH3CH2OH), and dimethyl ether (CH3OCH3) recorded in a variety of ice environments and for astronomically relevant temperatures, as needed to guide or interpret astronomical observations, specifically for upcoming James Webb Space Telescope observations.Methods. Fourier transform transmission spectroscopy (500–4000 cm−1/20–2.5 μm, 1.0 cm−1 resolution) was used to investigate solid acetaldehyde, ethanol and dimethyl ether, pure or mixed with water, CO, methanol, or CO:methanol. These species were deposited on a cryogenically cooled infrared transmissive window at 15 K. A heating ramp was applied, during which IR spectra were recorded until all ice constituents were thermally desorbed.Results. We present a large number of reference spectra that can be compared with astronomical data. Accurate band positions and band widths are provided for the studied ice mixtures and temperatures. Special efforts have been put into those bands of each molecule that are best suited for identification. For acetaldehyde the 7.427 and 5.803 μm bands are recommended, for ethanol the 11.36 and 7.240 μm bands are good candidates, and for dimethyl ether bands at 9.141 and 8.011 μm can be used. All spectra are publicly available in the Leiden Database for Ice.

Atomic Sulfur Anchored on Silicene, Phosphorene, and Borophene for Excellent Cycle Performance of Li-S Batteries.

Dissolution of intermediate lithium polysulfides (LiPS) is an inevitable obstacle for the solid sulfur-based cathode in Li-S batteries. For the first time, herein, atomic sulfur is incorporated into silicene, phosphorene, and borophene to intrinsically eliminate the dissolution of LiPS. The small molecular sulfur species are anchored on the silicene surface with stronger Si-S interaction than the P-S and B-S ones. Meanwhile, a high atomic sulfur coverage (63.1 wt %) is achieved in silicene and concomitantly stabilizes the silicene layer. For the S3-covered silicene, a high theoretical capacity of 857 mA h g-1 is achieved with slight dissolution of LiPS originated from the loss of interior S atoms that are not directly bound with silicene surface. By realizing the elemental S2 coverage on silicene with large surface area, the Li+ ions can react fast with the S2 species, leading to a high theoretical capacity of 891 mA h g-1 without dissolution and migration of the intermediate LiPS. Most interestingly, the discharge products of atomic layer of lithium sulfides on silicene surface exhibit completely different behaviors from the traditional discharge products of solid Li2S, which can function as effective adsorption and activation sites for the conversion of LiPS from long chain to short chain by accelerated redox reaction. The present study gains some key insights into how the atomic sulfur contributes to the intrinsic shuttle inhibition and offers a feasible way to design the atomic sulfur-based cathode materials of Li-S batteries with better electrochemical performance.

Ce in the +4 oxidation state: Anion photoelectron spectroscopy and photodissociation of small CexOyHz- molecules.

The anion photoelectron (PE) spectra of a range of small mono-cerium molecular species, along with the Ce2O4- and Ce3O6- stoichiometric clusters, are presented and analyzed with the support of density functional theory calculations. A common attribute of all of the neutral species is that the Ce centers in both the molecules and clusters are in the +4 oxidation state. In bulk ceria (CeO2), an unoccupied, narrow 4f band lies between the conventional valence (predominantly O 2p) and conduction (Ce 5d) bands. Within the CeO2-, CeO3H2-, and Ce(OH)4- series, the PE spectra and computational results suggest that the Ce 6s-based molecular orbital is the singly occupied HOMO in CeO2- but becomes destabilized as the Ce 4f-local orbital becomes stabilized with increasing coordination. CeO3-, a hyperoxide, undergoes photodissociation with 3.49 eV photon energy to form the stoichiometric neutral CeO2 and O-. In the CeO2-, Ce2O4- ,and Ce3O6- stoichiometric cluster series, the 6s destabilization with 4f stabilization is associated with increasing cluster size, suggesting that a bulk-like band structure may be realized with fairly small cluster sizes. The destabilization of the 6s-based molecular orbitals can be rationalized by their diffuse size relative to Ce-O bond lengths in a crystal structure, suggesting that 6s bands in the bulk may be relegated to the surface.

Mixed-Probe Simulation and Probe-Derived Surface Topography Map Analysis for Ligand Binding Site Identification.

Membrane proteins represent a considerable fraction of pharmaceutical drug targets. A computational technique to identify ligand binding pockets in these proteins is therefore of great importance. We recently reported such a technique called pMD-membrane that utilizes small molecule probes to detect ligand binding sites and surface hotspots on membrane proteins based on probe-based molecular dynamics simulation. The current work extends pMD-membrane to a diverse set of small organic molecular species that can be used as cosolvents during simulation of membrane proteins. We also describe a projection technique for globally quantifying probe densities on the protein surface and introduce a technique to construct surface topography maps directly from the probe-binding propensity of surface residues. The map reveals surface patterns and geometric features that aid in filtering out high probe density hotspots lacking pocketlike characteristics. We demonstrate the applicability of the extended pMD-membrane and the new analysis tool by exploring the druggability of full-length G12D, G12V, and G13D oncogenic K-Ras mutants bound to a negatively charged lipid bilayer. Using data from 30 pMD-membrane runs conducted in the presence of a 2.8 M cosolvent made up of an equal proportion of seven small organic molecules, we show that our approach robustly identifies known allosteric ligand binding sites and other reactive regions on K-Ras. Our results also show that accessibility of some pockets is modulated by differential membrane interactions.

Electrolyte Gradient-Based Modulation of Molecular Transport through Nanoporous Gold Membranes.

Nanopores, and nanoporous materials in general, are interesting for applications in chemical and biomolecular transport as pore sizes are on the same scale as the dimension of many (bio)chemical species. Many studies have focused on either single pores or small arrays of cylindrical pores, which are convenient in terms of their amenability toward computational modeling of transport phenomenon. However, the limited overall porosity may inhibit transport flux as well as the eventual implementation of these materials as active separation elements. Inspired by its relatively high porosity, we have explored nanoporous gold (NPG) as a membrane across which small molecular species can be transported. NPG offers a random, bicontinuous pore geometry, while also being inherently conductive and readily amenable to surface modification-attributes that may be enabling in the pursuit of size- and charge-based approaches to molecular separations. NPG was fabricated via a free-corrosion process whereby immersion of Au-containing alloys in concentrated nitric acid preferentially dissolves the less noble metals (e.g., Ni, Cu). Average pore diameters of 50 ± 20 nm were obtained as verified under scanning electron microscopy. NPG membranes were sandwiched between two reservoirs, and the selective transport of chemical species across the membrane in the presence of an ionic strength gradient was investigated. The flux of small molecules were monitored by UV-vis absorption spectrometry and found to be dependent upon the direction and magnitude of the ionic strength gradient. Moreover, transport trends underscored the effects of surface charge in a confined environment, considering that the pore diameters were on the same scale as the electrical double layer experienced by molecules transiting the membrane. Under such conditions, the transport of anions and cations through NPG was found to depend on an induced electric field as well as ion advection. Further electrical and surface chemical modulations of transport are expected to engender increased membrane functionality.

The Challenge of Thermal Deposition of Coordination Compounds: Insight into the Case of an Fe4 Single Molecule Magnet

Realization of well-controlled hybrid interfaces between solid surfaces and functional complex molecules can be hampered by the presence of contaminants originated by the fragmentation of fragile architectures based on the coordinative bond. Here, we present a morphological and spectroscopic analysis of submonolayer films obtained by sublimation of the [Fe4(L)2(dpm)6] (Fe4) single molecule magnet on different substrates. Though intact tetranuclear molecules can be transferred to surfaces, smaller molecular species are often codeposited. By comparison of substrates characterized by different reactivities, such as Au(111), Cu(100), and Cu2N, and employing a protocol of indirect exposure of the substrate, we infer that the observed fragments do not originate from the reaction of Fe4 molecules with the surface but rather are produced during Fe4 sublimation, which releases Fe(dpm)3 as a very volatile compound. Fe(dpm)3 undergoes substrate-dependent on-surface decomposition to final products that have been iden...

Spatial Localization and Quantitation of Androgens in Mouse Testis by Mass Spectrometry Imaging.

Androgens are essential for male development and reproductive function. They are transported to their site of action as blood-borne endocrine hormones but can also be produced within tissues to act in intracrine and paracrine fashions. Because of this, circulating concentrations may not accurately reflect the androgenic influence within specific tissue microenvironments. Mass spectrometry imaging permits regional analysis of small molecular species directly from tissue surfaces. However, due to poor ionization and localized ion suppression, steroid hormones are difficult to detect. Here, derivatization with Girard T reagent was used to charge-tag testosterone and 5α-dihydrotestosterone allowing direct detection of these steroids in mouse testes, in both basal and maximally stimulated states, and in rat prostate. Limits of detection were ∼0.1 pg for testosterone. Exemplary detection of endogenous steroids was achieved by matrix-assisted laser desorption ionization and either Fourier transform ion cyclotron resonance detection (at 150 μm spatial resolution) or quadrupole-time-of-flight detection (at 50 μm spatial resolution). Structural confirmation was achieved by collision induced fragmentation following liquid extraction surface analysis and electrospray ionization. This application broadens the scope for derivatization strategies on tissue surfaces to elucidate local endocrine signaling in health and disease.

Methyl Radical in Clathrate Silica Voids. The Peculiar Physisorption Features of the Guest-Host Molecular Dynamics Interaction.

EPR line shape simulations of CH3/SiO2 clathrates and comparison to CH3/N2O and CH3/SiO2 experiments reveal the motional conditions of the CH3 radical up to the unusual regime of its stability, the high-temperature diffusional regime, at 300 K. In the low-temperature region, the CH3 in clathrates is found to rotate around the in-plane axes even at as low temperatures as 3.8 K. However, nonrotating methyls performing only libration about the C2-axes as well as around the C3-axis are also found, proving the existence of special sites in the clathrate voids that begin to accumulate a significant fraction of methyl radicals at temperatures below approximately 7 K. A distinctive feature in the spectrum anisotropy and line width temperature profiles is found nearby 25 K, which is interpreted as the radical physisorption inside the voids that occurs with the sample temperature lowering. The unusual increase of the CH3/SiO2 clathrate EPR spectral width with temperature over approximately 120 K has its origin in repeated angular momentum vector alterations due to frequent collisions with the clathrate void walls between periodical free rotation periods. This relaxation mechanism resembles to spin-rotation interaction known only for small molecular species in nonviscous fluids but unknown earlier for methyl hosted in solids.

Abstract 4231: Analysis of FFPE treated clinical tissue sections obtained from human intraocular malignancy, uveal melanoma by mass spectrometry imaging (MSI)

Abstract Introduction Clinical research into human intraocular disease UM FFPE tissue sections is described. UM remains the most common intraocular malignancy in adults, with poor prognosis for UM within the choroid region and distant sites UM metastasis. Two imaging MS techniques Matrix Assisted Laser Desorption/Ionisation (MALDI) and Desorption Electrospray Ionisation (DESI) MSI were applied. Molecular profiles were obtained and analysed by multivariate statistical approaches, providing insight into the biochemical and biological differences/similarities within the patient sample cohort (n = 15). Methods Enucleations were collected over 6 years and subjected to the standard fixation and paraffin embedding protocols. In preparation for MS, 5 μm sections were produced with removal of the paraffin followed by heat induced antigen retrieval. MALDI MSI tissue sections were prepared by applying a matrix solution onto the tissue sections to help ionization of molecules directly from the tissue. All MSI experiments (MALDI and DESI) were carried out using a SYNAPT mass spectrometer (Waters Corporation, Manchester, UK). Multivariate analyses were performed using MATLAB (MathWorks, Inc., Natick, MA, US) and the Eigenvector PLS_Toolbox. Results Initial MALDI MSI images acquired with a spatial resolution of 100 μm x 100 μm in positive ion mode showed distinct spatial distribution of many molecular species throughout the choroid, cornea, retina, lens and UM tumor regions. Further MALDI MSI experiments using consecutive tissue sections at 50 μm x 50 μm spatial resolution show substantial variation in the spatial distribution of species within the low molecular mass range. DESI MSI experiments were carried out at 200 μm x 200 μm in negative ionization mode. Deprotonated molecular ions were detected from a variety of lipid related species, localized to specific regions within the eye including the tumor region. Multivariate analysis classified UM samples (good vs. poor prognosis). Using unsupervised PCA, an unbiased representation of the data was generated, with clear sample grouping and differentiation observed based upon tumor status. Use of the supervised PLS-DA technique provided even clearer separation between the selected samples, with tumor profiles displaying dominant discriminatory peaks. These peaks could be identified as sphingolipids and Lyso-phosphocholine, a phosphatidylcholine degradation product. Conclusions It was possible to analyze clinical research FFPE tissue sections by MALDI and DESI MSI, illustrating that specific small molecular species remained localized to certain tissue types including the UM tumor. Initial correlation with tumor status was determined from the statistical analysis of the MALDI MSI datasets. Citation Format: Laura M. Cole, Hardeep S. Mudhar, Karen Sisley, Andrew Peck, Mike Batey, Emmanuelle Claude, Malcolm Clench. Analysis of FFPE treated clinical tissue sections obtained from human intraocular malignancy, uveal melanoma by mass spectrometry imaging (MSI). [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4231.