Photocycloaddition reaction between 7,7,9-trimethyl-6,7-dihydrofuro[3,2-f]quinoline and thymidine 5′-monophosphate

Quenching of the triplet state of 7,7,9-trimethyl-6,7-dihydrofuro[3,2-f]quinoline (FDHQ) by thymidine 5??-monophosphate disodium salt (TMP) has been observed in the water-alcohol solution with a bimolecular rate constant close in value to the diffusion-limited constant (2.2 × 10⁹ L mol^?1 s^?1). The products of the steady-state photolysis of a FDHQ-TMP mixture in the water-alcohol solution have been isolated by HPLC and identified by mass spectrometry. Four isomers with a molecular weight of 580 Da equal to the sum of the molecular weights of FDHQ + TMP and with identical mass spectra are the major products of the photolysis. The fragmentation of the molecular ion for all the isomers gives an ion with a weight of 340 Da, indicating the cleavage of the saccharide residue and the formation of the rigid cyclobutane cycle as a result of interaction between the double bond of the nitrogen- or oxygen-containing heterocycle of FDHQ in the triplet state and the C(5)=C(6) double bond of TMP. Diadducts have not been found in the photolysis products. Possible structures of the isomeric products of interaction of FDHQ with TMP have been considered.     

Mass spectrometric monitoring of exhaled breath condensate proteome of a patient after lung transplantation

Analysis of samples of exhaled breath condensate (EBC) is a promising noninvasive method for the control of the status of the human respiratory system. In the present work, the proteome of the EBC samples received from a patient with lung dystrophy at different times before and after bilateral lung transplantation is analyzed by ion cyclotron resonance mass spectrometry. Qualitative protein composition of EBC samples obtained during the first month correlates with the clinical data on the acceptance of the transplanted lungs (allograft). Fifteen months after the lung surgery, the protein spectrum was similar to the normal composition of EBC proteins. This result agrees with the medical conclusion about normal lung functioning. The results suggest that the mass spectrometric monitoring of the protein spectra of EBC may be a tool for noninvasive pulmonological diagnostics.     

Conformational changes of ubiquitin during electrospray ionization as determined by in‐ESI source H/D exchange combined with high‐resolution MS and ECD fragmentation

In the paper, we have demonstrated the possibility of performing hydrogen/deuterium (H/D) exchange of proteins in the region of gas‐phase ion formation in an electrospray ion source by saturating the electrospray ionization source with vapors of a deuterating agent (D₂O or MeOD). In this region, charged droplets are shrinking and the protein ions transfer into the gas phase. As a model protein, we have used ubiquitin whose ion mobility spectrometry and gas‐phase H/D exchange in the vacuum part of a mass spectrometer demonstrated the presence of gas‐phase conformers with different cross sections and H/D exchange rates. In our experiments, we observed monomodal deuterium distributions for all solvents, charge states, desolvating capillary temperature and types of deuterating agent. Also, we found that the number of H/D exchanges increases with an increasing desolvating capillary temperature and decreasing charge state. We observed that solution composition (49 : 50 : 1 H₂O : MeOH : formic acid or 99 : 1 H₂O : formic acid) influences the charge‐state distribution but did not change the degree of H/D exchange for the same charge state. Electron‐capture dissociation fragmentation shows that higher charge states contain a segment that is protected from access by the deuterating agent. Copyright © 2014 John Wiley & Sons, Ltd.     

On the beam propagation through active media

An analytical iterative procedure has been established to determine the amplitude of a laser beam propagating through an active medium. The treatment is valid for both homogeneous and inhomogeneous broadening, and for arbitrary inhomogeneities of the parameters characterizing the active medium, namely, the refractive index, the small-signal gain and the saturation intensity. After a supplementary approximation, a thin-sheet gain approach is derived from the first iteration. The formalism enables us to provide analytical criteria for evaluating both the accuracy of each iteration and the propagation distances for which the thin-sheet solution can be used. This revised version was published online in November 2006 with corrections to the Cover Date.     

Label‐free cervicovaginal fluid proteome profiling reflects the cervix neoplastic transformation

Cervicovaginal fluid (CVF) is a valuable source of clinical information about the female reproductive tract in both nonpregnant and pregnant women. The aim of this study is to specify the CVF proteome at different stages of cervix neoplastic transformation by label‐free quantitation approach based on liquid chromatography tandem mass spectrometry (LC‐MS/MS) method. The proteome composition of CVF from 40 women of reproductive age with human papillomavirus (HPV)‐associated cervix neoplastic transformation (low‐grade squamous intraepithelial lesion [LSIL], high‐grade squamous intraepithelial lesion [HSIL], and CANCER) was investigated. Hierarchical clustering and principal component analysis (PCA) of the proteomic data obtained by a label‐free quantitation approach show the distribution of the sample set between four major clusters (no intraepithelial lesion or malignancy [NILM], LSIL, HSIL and CANCER) depending on the form of cervical lesion. Multisample ANOVA with subsequent Welch's t test resulted in 117 that changed significantly across the four clinical stages, including 27 proteins significantly changed in cervical cancer. Some of them were indicated as promising biomarkers previously (ACTN4, VTN, ANXA1, CAP1, ANXA2, and MUC5B). CVF proteomic data from the discovery stage were analyzed by the partial least squares‐discriminant analysis (PLS‐DA) method to build a statistical model, allowing to differentiate severe dysplasia (HSIL and CANCER) from the mild/normal stage (NILM and LSIL), and receiver operating characteristic (ROC) area under the curve (AUC) were obtained on an independent set of 33 samples. The sensitivity of the model was 77%, and the specificity was 94%; AUC was equal to 0.87. CVF proteome proved to be reflect the stage of cervical epithelium neoplastic process.     

Dichloromethane as solvent and reagent: a case study of photoinduced reactions in mixed phosphonium‐iodonium ylide

Several years ago the photoinduced reaction of mixed phosphonium‐iodonium ylides ( 1 ) with acetylenes ( 2 ) to give λ⁵‐phosphinolines ( 3 ) and substituted furans ( 4 ) was described. This reaction is one‐pot, metal‐free synthesis of heterocycles 3 and 4 with the yields of 40% to 80%. The reaction proceeds only in dichloromethane (DCM) at the high ylide concentrations (>0.01 mol/L). The product analysis by ³¹P NMR, electrospray ionization mass spectrometry, UV‐vis spectrophotometry, and the dynamic light scattering study of the self‐aggregation of the ylide in DCM showed a dual role of the solvent in the photoinduced reactions of mixed phosphonium‐iodonium ylide: (i) at the low ylide concentrations (<0.01 mol/L), the conjugated photoinitiation of the chain reaction in DCM results in the formation of chlorine‐containing products and (ii) at the high ylide concentrations (>0.01 mol/L), the photolysis mechanism is determined by self‐organization of the ylide molecules to give large stable aggregates in DCM, in which the target heterocycles are synthesized. Two important issues follow from the study. First, the annulation reaction between mixed phosphonium‐iodonium ylide and acetylenes occurs only when the reactive intermediates are in close proximity to one other, and, second, DCM is not inert reagent in reactions occurring with participation of radicals and in one form or another can participate in photoinduced radical reactions of various solutes.     

Conformations of cationized linear oligosaccharides revealed by FTMS combined with in‐ESI H/D exchange

Previously (Kostyukevich et al. Anal Chem 2014, 86, 2595), we have reported that oligosaccharides anions are produced in the electrospray in two different conformations, which differ by the rate of gas phase hydrogen/deuterium (H/D) exchange reaction. In the present paper, we apply the in‐electrospray ionization (ESI) source H/D exchange approach for the investigation of the oligosaccharides cations formed by attaching of metal ions (Na, K) to the molecule. It was observed that the formation of different conformers can be manipulated by varying the temperature of the desolvating capillary of the ESI interphase. Separation of the conformers was performed using gas phase H/D approach. Because the conformers have different rates of the H/D exchange reaction, the deuterium distribution spectrum becomes bimodal. It was found that the conformation corresponding to the slow H/D exchange rate dominates in the spectrum when the capillary temperature is low (~200 °C), and the conformation corresponding to the fast H/D exchange rate dominates at high (~400 °C) temperatures. In the intermediate temperature region, two conformers are present simultaneously. It was also observed that large oligosaccharide requires higher temperature for the formation of another conformer. It was found that the presence of the conformers considerably depends on the solvent used for ESI and the pH. We have compared these results with the previously performed in‐ESI source H/D exchange experiments with peptides and proteins. Copyright © 2015 John Wiley & Sons, Ltd.     

Optimization of ionization conditions for analysis of humic substances from natural waters using Electrospray Ionization Fourier Transform Ion Cyclotron Resonance mass spectrometry (ESI FTICR MS)

An approach to optimizing conditions of acquiring Electrospray Ionization Fourier Transform Ion Cyclotron Resonance mass spectra (ESI FTICR MS) was suggested. This method was employed to study the influence of cone voltage and the composition of the solution on peak intensity in ESI FTICR mass spectra of natural water humic substances. A presence of water in methanol solution was shown to reduce signal intensity significantly. The highest integral intensity of peaks selected was reached on 110 mg/l sample solution in acetonitrile and cone voltage 3.0 kV. The number of peaks to which molecular formulas were assigned, including doubly-charged peaks, was increased using these conditions.     

Simple Synthesis of Ruthenium π Complexes of Aromatic Amino Acids and Small Peptides

The interaction of [Ru(η⁶‐C₁₀H₈)(Cp)]⁺ (Cp=C₅H₅) with aromatic amino acids (L ‐phenylalanine, L ‐tyrosine, L ‐tryptophane, D ‐phenylglycine, and L ‐threo‐3‐phenylserine) under visible‐light irradiation gives the corresponding [Ru(η⁶‐amino acid)(Cp)]⁺ complexes in near‐quantitative yield. The reaction proceeds in air at room temperature in water and tolerates the presence of non‐aromatic amino acids (except those which are sulfur containing), monosaccharides, and nucleotides. The complex [Ru(η⁶‐C₁₀H₈)(Cp)]⁺ was also used for selective labeling of Tyr and Phe residues of small peptides, namely, angiotensin I and II derivatives.     

Early diagnosis of lung cancer based on proteome analysis of exhaled breath condensate

A comparative study of the exhaled-breath-condensate (EBC) proteome that was obtained for four donor groups was carried out using ion cyclotron resonance mass spectrometry with electrospray ionization. The groups included subjects with diagnosed lung cancer, chronic obstructive pulmonary disease, community-acquired pneumonia, and healthy nonsmoking control subjects. More than 300 proteins were identified, while 19 of them were found in the EBC samples of the donors who were diagnosed with lung cancer in the early stages and are potentially significant in the development of a diagnostic lung-cancer biomarker panel. It was shown that the EBC protein profiles of different donor groups can be distinguished. It may be possible to highlight a specific protein group that is typical for certain conditions/diseases of the respiratory system. Thus, the EBC analysis could be a promising non-invasive method for early diagnosis of lung cancer.