The Study of Derivatization Prior MALDI MSI Analysis—Charge Tagging Based on the Cholesterol and Betaine Aldehyde

Mass spectrometry imaging is a powerful tool for analyzing the different kinds of molecules in tissue sections, but some substances cannot be measured easily, due to their physicochemical properties. In such cases, chemical derivatization could be applied to introduce the charge into the molecule and facilitate its detection. Here, we study cholesterol derivatization with betaine aldehyde from tissue slices and evaluate how different sample preparation methods influence the signal from the derivatization product. In this study, we have tested different solutions for betaine aldehyde, different approaches to betaine aldehyde deposition (number of layers, deposition nozzle height), and different MALDI matrices for its analysis. As a result, we proved that the proposed approach could be used for the analysis of cholesterol in different tissues.     

Structure and vibrational spectra of the bis(betaine)-selenic acid molecular crystal

The crystal structure of bis(betaine)-selenic acid has been determined by X-ray diffraction as orthorhombic, space group Pbca, with a = 11.591(2), b = 22.930(5), c = 12.045(2) Å and Z = 8. The crystal comprises hydrogen selenate ions, HSeO⁻₄, and two distinct betaine molecules, which are held together into a complex by short hydrogen bonds. One of the betaine molecules is present as the zwitterion form (CH₃)₃N⁺---CH₂---COO⁻ and the second occurs as the protonated form (CH₃)₃N⁺---CH₂---COOH. Powder FTIR and Raman spectra were measured. An assignment of the observed bands to vibrations of the hydrogen bonds and internal vibrations of the hydrogen selenate ion and the betaine molecules is proposed.     

Betaine 0.77‐perhydrate 0.23‐hydrate and common structural motifs in crystals of amino acid perhydrates

The title compound, betaine 0.77‐perhydrate 0.23‐hydrate, (CH₃)₃N⁺CH₂COO⁻·0.77H₂O₂·0.23H₂O, crystallizes in the orthorhombic noncentrosymmetric space group Pca2₁. Chiral molecules of hydrogen peroxide are positionally disordered with water molecules in a ratio of 0.77:0.23. Betaine, 2‐(trimethylazaniumyl)acetate, preserves its zwitterionic state, with a positively charged ammonium group and a negatively charged carboxylate group. The molecular conformation of betaine here differs from the conformations of both anhydrous betaine and its hydrate, mainly in the orientation of the carboxylate group with respect to the C—C—N skeleton. Hydrogen peroxide is linked via two hydrogen bonds to carboxylate groups, forming infinite chains along the crystallographic a axis, which are very similar to those in the crystal structure of betaine hydrate. The present work contributes to the understanding of the structure‐forming factors for amino acid perhydrates, which are presently attracting much attention. A correlation is suggested between the ratio of amino acid zwitterions and hydrogen peroxide in the unit cell and the structural motifs present in the crystal structures of all currently known amino acids perhydrates. This can help to classify the crystal structures of amino acid perhydrates and to design new crystal structures.     

1,4-dimethyl-3,6-dioxo-1,2,4,5-tetrazin-1-IUM-5(4h)-id,a new six-membered heterocyclic betaine

The preparation, the spectroscopic characterization, the crystal structure and chemical reactions of the new six-membered heterocyclic betaine2 are reported; 2 is a representative of a possibly large group of yet unkonwn betaines of the general structure 8.     

Syntheses and Crystal Structures of Two New Ag(Ⅰ) Complexes with Betaine Derivative: Structure Changes via Metal-to-ligand Ratio

Two new Ag(I) complexes {Ag2(L)(NO3)(H2O)}n(1) and {Ag(L)}n·nH2O(2) have been synthesized via the reaction of silver nitrate and betaine derivative 1-carboxymethylpyridinium-3-carboxylate(L) by only changing the metal-to-ligand ratio. The results of X-ray crystallographic analysis indicate that complexes 1 and 2 both crystallize in the monoclinic space group P21/c with a = 5.0809(14), b = 17.390(5), c = 13.399(4), β = 91.677(5)o, V = 1183.4(6)3, Z = 4, Mr = 475.90, Dc = 2.671 g/cm3, F(000) = 912, μ = 3.352 mm-1, S = 1.259, the final R = 0.0320 and wR = 0.0831 for 2036 observed reflections with I 2σ(I) for 1 and a = 12.180(2), b = 5.0283(10), c = 14.396(3), β = 94.87(3)o, V = 878.5(3)3, Z = 4, Mr = 306.02, Dc = 2.314 g/cm3, F(000) = 600, μ = 2.294 mm-1, S = 1.053, the final R = 0.0283 and wR = 0.0684 for 2011 observed reflections with I 2σ(I) for 2. Complexes 1 and 2 both feature a unique 2D structure. For 1, the 2D undulated network consists of 1D infinite helical chains running parallel to the b axis, while for 2, the 2D network is made up of 1D tubes along the b axis. Moreover, the Ag…Ag interactions in complexes 1 and 2 are also discussed.     

Synthesis and Crystal Structure of a Cyano-bridged Bimetallic Complex[La(betaine)_2(H_2O)_6Fe(CN)_6]·2H_2O

1 INTRODUCTION In the last decade, cyano-bridged Prussian Blueanalogues[1] have been intensively studied from theviewpoint of application as functionalized molecule-based magnets[2], chemical sensor materials[3], fluo-rescent materials[4] and zeolitic-type materials[5, , 6]etc. In 1976, a series of cyano-bridged three-dimen-sional rare earth hexacyanometalates(IIILnM(CN)6?nH2O (M = Fe or Cr, n = 4 or 5) were crystallized andsubjected to single-crystal X-ray analysis[7]. …     

Synthesis and Crystal Structure of a Cyano-bridged Bimetallic Complex [La(betaine)2(H2O)6Fe(CN)6]·2H2O

The title complex [La(betaine)2(H2O)6Fe(CN)6](2H2O (betaine = (CH3)3NCH2CO2) has been synthesized and characterized by X-ray single-crystal structure analysis. The crystal crystallizes in monoclinic, space group P21/n with a = 15.793(5), b = 8.927(3), c = 22.257(7) (A), β = 110.147(5)°, C16H38FeLaN8O12, Mr = 729.31, Z = 4, V = 2946.0(15) (A)3, Dc = 1.640 g/m3, μ(MoKα) = 1.988 mm-1, F(000) =1476, R = 0.0388 and wR = 0.0827 for 4237 observed reflections (I > 2σ(I)). The La3+ ion is nine-coordinated by one cyano nitrogen atom and eight oxygen atoms of two betaine and six water molecules. Each complex molecule is connected to form a 3D network structure by some O-H…O and O-H…N hydrogen bonds.     

Heteroorganic betaines. 7. Synthesis and structure of a germanium-containing organophosphorus betaine Et3P+—CHMe—GeMe2—S–

Germanium-containing organophosphorus betaine Et₃P⁺—CHMe—GeMe₂—S^– was synthesized by the reaction of hexamethylcyclotrigermatrithiane with Et₃P=CHMe. The structure of the betaine was established by X-ray diffraction analysis and multinuclear NMR spectroscopy. In the crystal, the P⁺—C—Ge—S^– main chain of the molecule adopts a folded cis-gauche conformation due to strong Coulomb interactions between the anionic and cationic centers. The equilibrium geometry of the isolated molecule was calculated within the framework of the density functional theory (the PBE functional, the TZ2P basis set). The calculated geometric characteristics are in qualitative agreement with the X-ray data. The structure of the betaine is compared with the structure of its silicon-containing analog studied previously.     

Quadrupolar [14](meta-ortho)2azolophanes. Intramolecular C-H…N and to Water C-H…O hydrogen bonding revealed by X-ray diffraction

The first X-ray crystallographic diffraction of an example of the title heterophanes built up from heterocyclic betaine subunits is reported and its quadrupolar character is confirmed. The crystal packing of 2·4H₂O is mainly governed by hydrogen-bonding networks, strong intermolecular interactions with water together with weak interactions, either intramolecular or with water.     

Synthese und Struktur von 1,3‐Diisopropyl‐4,5‐dimethylimidazolium‐2‐sulfonat: Ein Carbenaddukt des Schwefeltrioxids

Synthesis and Structure of 1,3‐Diisopropyl‐4,5‐dimethylimidazolium‐2‐sulfonate: A Carbene Adduct of Sulfur Trioxide [1] The stable betaine 1,3‐diisopropyl‐4,5‐dimethylimidazolium‐2‐sulfonate ( 5 ) is obtained through hydrolysis of the 2‐chloro‐1,3‐diisopropyl‐4,5‐dimethylimidazolium chloro‐ sulfite salt ( 4 b ) in the presence of cyanide. The crystal structure analysis of 5 is reported.     

Non-centrosymmetric betaine–selenious acid crystal: Vibrational,X-ray,calorimetric, and dielectric studies

Piezoelectric crystal of betaine–selenious acid (abbreviated as B–H₂SeO₃) was studied at various temperatures by X-ray diffraction, differential scanning calorimetry, dielectric and vibrational spectroscopy methods. The latter was made by applying polarized techniques for the single crystal samples (Raman, infrared transmission and reflection spectra) and for the polycrystalline samples as well. B–H₂SeO₃ crystallizes in non-centrosymmetric space group (Fdd2) of orthorhombic system and does not reveal any phase transition. The high piezoelectric effect makes this crystal a candidate for nonlinear optical applications. Detailed analysis of the polarized vibrational spectra in relation to the B–H₂SeO₃ crystal structure is presented.     

Polarised vibrational spectra of betaine ortho-phosphoric acid complex. Part II. Phase transitions studies

Polarised infrared transmission and Raman spectra of betaine ortho-phosphoric acid crystal in temperature ranges 13-393 and 13-300 K, respectively are reported and discussed in relation to phase transitions: antiferrodistortive at T(c1) = 365 K and antiferroelectric at T(c3) = 81 K. The spectra are consistent with unit cell doubling below T(c3). The participation of all hydrogen bonds apparent in the crystal in the antiferroelectric phase transition was shown. Quite large freedom of -N(CH(3))(3) groups reorientation in the antiferroelectric phase was detected. No changes were found in the transmission spectra taken in the vicinity of the antiferrodistortive phase transition temperature.     

X-ray diffraction,spectroscopic (IR,Raman) and DSC studies of bis(betainium) p-toluenesulfonate monohydrate crystal

Bis(betainium) p-toluenesulfonate monohydrate (abbreviated as BBTSH) was studied at various temperatures by X-ray diffraction, differential scanning calorimetry and vibrational spectroscopy methods. DSC curves of BBTSH show a peak at about 349 K which corresponds to water escape from the crystal, and reveal the “cold crystallization” phenomenon. BBTSH crystallizes in the P2₁/c space group of monoclinic system. After heating above 349 K the compound dehydrates, the crystal system changes to triclinic, the monocrystalline samples become non-merohedral twins. The BBTSH crystal comprises p-toluenesulfonic anions, monoprotonated betaine dimers and water molecules. Three kinds of hydrogen bonds are present in the crystal: strong, asymmetric and almost linear OH⋯O hydrogen bond (R(O⋯O) = 2.463(2) Å), weak O_wH⋯O hydrogen bonds (R(O_w⋯O) = 2.820(2) − 2.822(2) Å) and weak CH⋯O hydrogen bonds (R(C⋯O) = 3.295(2) − 3.416(2) Å). The ν_aOHO vibration of the strongest hydrogen bond in the crystal gives rise to an intense broad absorption with numbers of transmission windows in the low wavenumber region of the infrared spectra. Coupling between νCO stretching vibrations of two COO groups of the betaine dimer was detected. The process corresponding to the loss of water is accompanied by the breakage of strong OH⋯O hydrogen bonds in betaine dimers and rearrangement inside half of the betaine dimers. This rearrangement results in formation of the new betaine dimers with OH∙∙∙O hydrogen bond of similar strength as corresponding bond in the hydrated form (BBTSH).     

Simultaneous determination of trimethylamine and trimethylamine N‐oxide in mouse plasma samples by hydrophilic interaction liquid chromatography coupled to tandem mass spectrometry

A method was developed that applies hydrophilic interaction liquid chromatography with tandem mass spectrometry in the multiple reaction monitoring mode to separate and accurately quantify trimethylamine and trimethylamine N‐oxide in a single chromatographic run. This was achieved by converting trimethylamine to ethyl betaine, which is less volatile and hence results in greatly improved quantitation. Ethyl betaine also gives a similar response to trimethylamine N‐oxide using positive‐ion electrospray ionization mass spectrometry. It is readily separated from trimethylamine N‐oxide by hydrophilic liquid chromatography in a 5 min run and with improved peak shape compared to underivatized trimethylamine. Validation of the method yielded a limit of detection (S/N ≥ 3) of 0.5 ng/mL for trimethylamine and 0.25 ng/mL for trimethylamine N‐oxide. Method accuracies of 91.4–105.3% with precisions of 0.4–5.5% were obtained for standard mixtures over the range of 2.5–500 ng/mL. Recoveries measured for the extraction of trimethylamine and trimethylamine N‐oxide spikes into mouse plasma were both >90%. The method, which simultaneously measures trimethylamine and trimethylamine N‐oxide, was successfully applied to mouse plasma samples and could be adapted for use with other biological fluids.     

Synthesis of Ammonium‐ and 4‐Dimethylaminopyridinium Amidofluorophosphates and Crystal Structure of [DMAPH][PO2F(NH2)]

NH₄[PO₂F(NH₂)] has been prepared by the reaction of a betaine py·PO₂F with excess ammonia in acetonitrile solution, while the ammonolysis of DMAP·PO₂F with a stoichiometric amount of NH₃ yields [DMAPH][PO₂F(NH₂)]. The crystal structure of the latter was determined by single‐crystal X‐ray diffraction, which revealed that the anions [PO₂F(NH₂)]^— are linked to infinite chains by double N—H···O bridges. Additional strong N—H···O bridging bonds connect each anion with its [DMAPH]⁺ counterion. The formation of a new betaine NH₃·PO₂F in the solution of py·PO₂F in liquid ammonia was proved by ³¹P NMR spectroscopy and by identification of its hydrolysis products.     

Photoinitiated processes in 1-p-tolylsulfonylazo-2,4,6,8-tetrakis(tert-butyl)phenoxazine

New photochromic compound 1-p-tolylsulfonylazo-2,4,6,8-tetrakis(tert-butyl)phenoxazine containing the intramolecular hydrogen bond NH...N and the corresponding model structures 2,4,6,8-tetrakis(tert-butyl)-1-(veratroylazo)phenoxazine and 2,4,6,8-tetrakis(tert-butyl)-N-acetyl-1-(p-tolylsulfonylazo)phenoxazine were synthesized and studied. The data obtained suggested the mechanism of the photoreaction resulting in the accumulation of betaine 1-hydroxy-2,4,6,8-tetrakis(tert-butyl)-10-tolylsulfonylphenoxazin-9-one. The photochromic transformations in the molecule under study are due to intramolecular proton phototransfer followed by E–Z-isomerization about the N–N bond and the formation of betaine 1-hydroxy-2,4,6,8-tetrakis(tert-butyl)-10-tolylsulfonylphenoxazin-9-one. The molecular and crystal structure of the photoproduct was studied by X-ray analysis.     

Synthesis and properties of phosphabetaine structures: IV. 3-(triphenylphosphonio)propanoate in reactions with dipolar electrophilic reagents

Reactions of 3-(triphenylphosphonio)propanoate with heterocumulenes, such as phenyl isocyanate and dicyclohexylcarbodiimide, we studied under the assumption that they proceed by nucleophilic addition and 1,4-dipolar cycloaddition schemes. Quantum-chemical calculations show that the σ⁵-phosphorane cycloadduct of the betaine with isocyanate is thermodynamically preferred over its isomeric zwitter-ionic adduct. However, the experimental evidence suggests that the reaction with phenyl isocyanate involves nucleophilic addition of the betaine to isocyanate followed by hydrolysis to firm finally a complex of the starting betaine with diphenylurea. The structure of the complex was established by X-ray diffraction analysis. The revealed above controversy is explained by a high protophilicity of betaine structures, which is also confirmed by the results of the reaction of the betaine with carbodiimide.     

Spectrophotometric determination of water in organic solvents with solvatochromic dyes

The correlation between the absorbance at a fixed wave-length of a betaine dye in an organic solvent and the water content of the same solvent has been investigated. The betaine dyes investigated are 2,4,6-triphenyl-N-(3,5-diphenyl-4-hydroxyphenyl)pyiidinium betaine (I), 1-methyl-8-hydroxyquinolinium betaine (II), 1-methyl-6-hydroxyquinolinium betaine (III) and 2-methyl-5-isoquinolinium betaine (IV), and the organic solvents are ethanol, isopropanol, acetone, dioxan, acetonitrile and pyridine. The possibility of determining a trace amount of water in an organic solvent is demonstrated. The sensitivity of the method depends on solvent and dye but for example, 0.06 mg of water in 1 ml of acetonitrile can be detected with III with an ordinary spectrophotometer. The limitations of practical applications are discussed.     

Evaluation of potential cationic probes for the detection of proline and betaine

Osmoregulants are the substances that help plants to tolerate environmental extremes such as salinity and drought. Proline and betaine are two of the most commonly studied osmoregulants. An indirect UV CE method has been developed for simultaneous determination of these osmoregulants. A variety of reported probes and compounds were examined as potential probes for the indirect detection of proline and betaine. Mobility and UV‐absorption properties highlighted sulfanilamide as a potential probe for indirect analysis of proline and betaine. Using 5 mM sulfanilamide at pH 2.2 with UV detection at 254 nm, proline and betaine were separated in less than 15 min. The LODs for proline and betaine were 11.6 and 28.3 μM, respectively. The developed method was successfully applied to quantification of these two osmoregulants in spinach and beetroot samples.     

On the interaction of electrons with betaine zwitterions

Betaine is a permanent zwitterion. The molecular betaine anion has been generated in a hybrid, infrared desorption-electron photoemission source and its photoelectron spectrum recorded. The photoelectron spectrum of the betaine anion is characteristic of a dipole bound anion, and its vertical detachment energy was measured to be 0.29+/-0.03 eV. Calculations by Rak, Skurski, and Gutowski [J. Chem. Phys. 114, 10673 (2001)] had found the betaine anion to be a dipole bound anion with a vertical detachment energy of 0.28 eV. We also measured the vertical detachment energy of deprotonated betaine to be approximately 1.9 eV.