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In 139 patients with verified gastric cancer, the infiltration of the postoperative material with CD8 + cells was analyzed. Automated morphometric analysis of immunostained slides was performed separately in different specimen sites (tumor center, invasive edge, and peritumoral mucosa). The mean area of infiltrating CD8 + cells in the tumor center and in the invasive edge was not predictive, while in the peritumoral mucosa it provided a new negative predictive factor (hazard ratio 2.10; confidence interval 0.87-4.92, Cox regression) reliably associated with the TNM stage (hazard ratio 1.91; confidence interval 0.91-4.61, Cox regression)., (© 2023. Springer Science+Business Media, LLC, part of Springer Nature.)

Cancer-associated fibroblasts (CAFs) - mesenchymal cells in the tumor stroma, play one of the leading roles in tumor progression in many different tumors, including colorectal cancer. Scientists have described many markers for CAFs, but none of them is specific. We performed immunohistochemistry tests using five antibodies (αSMA, POD, FAP, PDGFRα, PDGFRβ) to investigate CAFs in three zones of 49 colorectal adenocarcinomas: apical, central, and invasive edge. We revealed the reliable correlation between high PDGFRβ and PDGFRα value in the apical zone and deeper invasion (T3-T4) ( p  = 0.0281 and p  = 0.0137). High αSMA level in apical zone ( p  = 0.0001), αSMA level in central zone ( p  = 0.019), POD level in apical zone ( p  = 0.0222), POD level in central zone ( p  = 0.0206) and PDGFRβ level in apical zone ( p  = 0.014) correlated reliably with the presence of metastasis in lymphatic nodules. For the first time, focused on the inner layer of CAF adjacent to tumor complexes. We observed that cases with inner αSMA expression were significantly more often ( p  = 0.023) characterized by the presence of regional lymph node metastasis compared with cases with mix of CAF markers ( p  = 0.007) and with cases with inner POD expression ( p  = 0.024). The found relationships between the level of markers and the presence of metastases indicate their clinical significance., (© The Author(s), under exclusive licence to Indian Association of Surgical Oncology 2022, Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

The adaptation of methodology of expert selection of indicators for integral evaluation of efficiency of organization of medical care on profile "pediatrics" at the level of the Subject of the Russian Federation. The study was organized as expert survey using structured interview technique. At the first stage, primary selection of indicators carried out. At the second stage, selection of experts in accordance with inclusion criteria and assessment of level of expert competence was organized. Then, criteria of expert evaluation of significance of selected indicators in accordance with international principles applied in of bench-marking systems construction were formulated. The Kendall's concordance coefficient (W) was calculated for quantitative assessment of degree of agreement between the experts answers. The non-parametric Friedman test was applied to evaluate significance of differences. The indicators with high degree of agreement between opinions of experts and availability of statistical significance according concordance coefficient are recommended as indicators for assessment of efficiency of organization of medical care of children at the level of the Subject of the Russian Federation. The following indicators satisfy these requirements: mortality of children aged 0-17 years (per 100 000 of population of corresponding age), mortality of children aged 0-1 year (per 1000 live births), mortality of children aged 0-4 years (per 1000 live births), support of population with beds for children, percentage of children aged 0-17 years under dispensary observation with diagnosis established for the first time. The study permitted to select indices (indicators) that can be applied both for integral rating of the Subjects of the Russian Federation and in formation of Federal projects or departmental target programs in pediatrics. The study results can also be applied in development of system of monitoring efficiency of implementation of these projects and programs.

Aim of the study - determination of approaches to the formation of the rating of the constituent entities of the Russian Federation, reflecting the state of medical care in various profiles (the effectiveness and quality of medical care in various profiles). The study included a comprehensive analysis of the structure and content of the reports based on the results of national medical research centers field events using classification and grouping methods. Assessment of the advantages and disadvantages of the used variants of the methodology for forming the subject rating of the Russian Federation used the method of selective SWOT analysis of methodologies published in the form of scientific articles. Further, based on the results obtained, the main requirements for building a rating system for subjects of the Russian Federation based on the indicators of efficiency (performance) and the quality of medical care were formulated. The possibility of applying international experience in building benchmarking systems in the Russian Federation is analyzed and requirements are formulated for building a subject rating system of the Russian Federation, taking into account the peculiarities of the domestic healthcare system. There are 3 main methodological approaches to the formation of the subject rating of the Russian Federation: a quantitative score rating assessment of quantitative indicators without weight coefficients, a qualitative rating assessment of the effectiveness of medical care in a profile without weight coefficients, and a mixed score-rating assessment of quantitative and qualitative indicators using weight coefficients determined only by an expert method. It has been established that many of the existing approaches to the formation of the subject rating of the Russian Federation are based on a combination of a point rating and weight coefficients established by an expert method. Since different indicators have different contributions to the final integral value of the subject rating of the Russian Federation, it is advisable to conduct another study to establish weight coefficients for indicators.

Objective: Assessment of the incidence of EBV-associated gastric adenocarcinomas in a sample of Russian patients, as well as clarification of the clinical and morphological characteristics and median survival of patients with EBV-associated gastric cancer., Material and Methods: We used samples of surgical material from 282 patients with a verified diagnosis of gastric cancer. Each sample was stained by in situ hybridization using primers for the Epstein-Barr virus-encoded small RNAs (EBER). The results obtained were compared with the main clinical and morphological characteristics of gastric cancer., Results: The detection rate of EBV-associated gastric adenocarcinoma in our sample was 9.57%. EBER-positive tumors much more often ( p =0.021) belong to the intermediate type according to the P. Lauren classification (66.67%) in comparison with EBER-negative tumors (38.82%). EBER-positive tumors significantly more often ( p =0.035) belong to high-grade tumors - 75.00% in comparison with EBER-negative tumors (52.13%). The overall median survival of all patients with EBER-positive tumors (53.5 months) was higher compared to the overall median survival of all patients with EBER-negative tumors - 36.5 months ( p =0.5379). The median survival of patients with EBER-positive stage III tumors (30.0 months) was also higher compared to that for patients with EBER-negative tumors - 20.0 months ( p =0.5622). It was found that a single EBER status is not a significant prognostic factor (HR=1.0143; CI: 0.9897-1.0196)., Conclusion: Separately taken EBER-status is not a significant independent prognostic factor and can be considered only in conjunction with the «classical» clinical and morphological characteristics, primarily with the stage of the tumor process, since it is they that determine the prognostic properties of the tumor.

Background: More than 80% of pathologists suffer from various manifestations of disorders of the musculoskeletal system. The daily duties of pathologists include several hours of work at a microscope and a computer. Microscopes are often not optimized for ergonomics and do not allow the doctor to take the correct sitting position, most often working with a microscope requires leaning forward., Objective: To study the ergonomic properties of the workplace of a pathologist and develop specific practical recommendations for long-term work at a microscope., Material and Methods: The study included microscopes with an adjustable and non-adjustable angle of inclination of the tube and height-adjustable chairs. We identify following ergonomic parameters: pathologist height; angle of inclination of the back of the chair; angle of inclination of the microscope tube; angle of inclination of the neck; chair height. The study included 21 participants. Statistical processing and analysis were made using single-factor and multifactorial correlation analysis., Results: A strong positive linear correlation was identified ( r =0.80; p <0.05) between the height of test person and angle of inclination of the microscope tube. A strong positive linear correlation was established ( r =0.91; p <0.05) between the test person height and the angle of inclination of the neck for microscopes with non-adjustable 31°-angle of inclination of the tube. For microscopes with non-adjustable 45°-angle of inclination of the tube a strong polynomial correlation of the second degree ( r =0.85; p <0.05) was found. A moderate negative linear correlation was found between the height of the pathologist and his tilt angle neck with both adjustable and non-adjustable tube angle of the microscope., Conclusion: In this study for the first-time exact correlation dependencies between key ergonomic parameters of pathologist's workplace were evaluated. This study showed that only microscopes with an adjustable angle of inclination of the tube allow to achieve an optimal body position.

Objective: Development of original methodological approaches to annotation and labeling of histological images in relation to the problem of automatic segmentation of the layers of the stomach wall., Material and Methods: Three image collections were used in the study: NCT-CRC-HE-100K, CRC-VAL-HE-7K, and part of the PATH-DT-MSU collection. The used part of the original PATH-DT-MSU collection contains 20 histological images obtained using a high performance digital scanning microscope., Each image is a fragment of the stomach wall, cut from the surgical material of gastric cancer and stained with hematoxylin and eosin. Images were obtained using a scanning microscope Leica Aperio AT2 (Leica Microsystems Inc., Germany), annotations were made using Aperio ImageScope 12.3.3 (Leica Microsystems Inc., Germany)., Results: A labeling system is proposed that includes 5 classes (tissue types): areas of gastric adenocarcinoma (TUM), unchanged areas of the lamina propria (LP), unchanged areas of the muscular lamina of the mucosa (MM), a class of underlying tissues (AT), including areas of the submucosa, own muscular layer of the stomach and subserous sections, image background (BG). The advantage of this marking technique is to ensure high efficiency of recognition of the muscularis lamina (MM) - a natural «line» separating the lamina propria of the mucous membrane and all other underlying layers of the stomach wall. The disadvantages of the technique include a small number of classes, which leads to insufficient detailing of automatic segmentation., Conclusion: In the course of the study, an original technique for labeling and annotating images was developed, including 5 classes (types of tissues). This technique is effective at the initial stages of teaching mathematical algorithms for the classification and segmentation of histological images. Further stages in the development of a real diagnostic algorithm to automatically determine the depth of invasion of gastric cancer require the correction and development of the presented method of marking and annotation.

Background: Diabetes mellitus (DM) is a significant predictor of atherosclerosis, cardiovascular disease, and cardiovascular mortality. It is known that atherosclerosis occurs earlier in patients with diabetes, reducing the duration of their life. Leptin as well as other inflammatory markers can contribute to the progression of atherosclerosis in patients with DM, participate in the development of a local inflammatory reaction., Aim: Determine the cells immunophenotype of atherosclerotic plaques in patients with diabetes., Materials and Methods: We analyzed 24 patients (20 men and 4 women), who underwent aortofemoral bypass, femoral-tibial bypass or carotid endarterectomy. During the operation, a fragment of the arterial wall with an atherosclerotic plaque was obtained for further immunohistochemical studies. Five histologic plaque characteristics (CD68+, -SMA, CD34, leptin and leptin receptor) were compared., Results: No difference in the expression of CD68 (p=0.922), -SMA (p=0.192), CD34 (p=0.858), leptin receptor (p=0.741) and leptin (p=0.610) in atherosclerotic plaques were observed between patients with and without DM. The lack of significant differences between the two groups was possibly due to the small number of observations with DM. In particular, when assessing the expression of selected markers in atherosclerotic plaques, patients with DM showed significantly more leptin receptors than patients without DM (2160.716 and 1205.88 respectively); and also significantly less CD68+ (0.39 and 0.98 respectively) and -SMA+ (6.5 and 13.5 respectively)., Conclusion: Based on the expression of CD68, -SMA, CD34, leptin receptor and leptin, no significant differences were observed in atherosclerotic plaque between patients with and without DM. At the same time, despite the limitations of the study (a small number of patients, moderate severity of DM, elderly patients in the DM group), we found a tendency in the increased number of leptin receptors and a decreased number of -SMA+, CD68+ in DM atherosclerotic plaques. Further study needed, taking into account the limitations of this work.

The Aim of the Study: Is to establish the relationship between the persistence of viral antigens of the Epstein-Barr virus (EBV) and the cellular composition of the immune microenvironment of tumor tissue and the mucous membrane of peritumoral area in gastric cancer., Material and Methods: We used samples of surgical material from 55 patients with a verified diagnosis of gastric cancer. The expression of CD4, CD8, CD68, CD1a and LMP-1 was assessed. The results were assessed by the morphometric method. We selected three fields of view (magnification x200) in tumor tissue and in peritumoral areas separately and counted an absolute number of cells with positive staining with further calculation of the average number of cells and the median., Results: LMP-1-negative tumors with LMP-1 expression in epithelium of peritumoral area were characterized by the highest density of CD4+ lymphocyte infiltration in the central part of the tumor; the highest density of CD8+ lymphocyte infiltration in the mucous membrane of peritumoral area ( p =0.0190); the highest density of infiltration by macrophages in the mucous membrane of peritumoral area ( p =0.2492); the highest density of infiltration by CD1a+ cells in the mucous membrane of peritumoral area ( p =0.1503). The highest density of infiltration with CD1a+ cells was characteristic for LMP-1-positive and LMP-1-negative tumors ( p =0.0813). The persistence of the LMP-1 viral antigen in the glandular epithelium of the peritumoral area in our sample does not have a statistically significant effect on the prognosis of the disease (RR=1.7718; p =0.0885) but there is a tendency towards a negative predictive value., Conclusion: High density of infiltration of glandular epithelium of peritumoral area with the expression of LMP-1 by CD4+ and CD8+ lymphocytes is most likely associated with the activation of the cellular immune response and may be one of the signs of the persistence of viral antigens. It was shown for the first time that the phenomenon of persistence of the LMP-1 viral antigen is characterized by a trend towards negative predictive value for patients with gastric cancer.

Objective: To determine the level of E-cadherin expression in tumor emboli, to compare it with expression in a tumor, to determine the dependence of E-cadherin expression in tumor emboli on the clinical and morphological characteristics of gastric cancer., Material and Methods: We used samples of surgical material from 280 patients with a verified diagnosis of gastric cancer. E-cadherin expression was determined by immunohistochemical method. The results of the reactions were assessed semi-quantitatively and compared with the main clinical and morphological characteristics of gastric cancer (histological type according to the WHO classification 2019, histological type according to the classification of P. Lauren, clinical stage, depth of invasion (T), number of metastases in lymph nodes (N), presence or/absence of distant metastases (M), tumor localization in the stomach)., Results: Among 280 cases of cancer, emboli were detected only in 67 cases, used for further analysis. The rest of the samples were excluded from the analysis, since emboli did not get into the sections during the cutting of immunohistochemical preparations. The expression of E-cadherin in tumor emboli was significantly higher ( p <0.001) than in tumor tissue. At the same time, no cases identified where the level of E-cadherin decreased in emboli compared to the tumor. A significant increase in the expression of E-cadherin in tumor emboli compared to the primary tumor was noted for all histological types according to WHO 2019, for intermediate and diffuse types according to the P. Lauren classification ( p <0.001). Comparison of expression in emboli and tumors for neoplasms with different depths of invasion (T), different stages and different localizations did not reveal statistically significant differences. An increase in the expression of E-cadherin in emboli compared to tumors was characterized by a higher level of significance in the presence of metastases (N1, N2, N3a, N3b; p <0.001) than in the absence of metastases (N0; p =0.016)., Conclusion: The study revealed a statistically significant increase in the expression of E-cadherin in tumor emboli compared to the primary tumor, which is evidence of its important role in maintaining the integrity of emboli and tumor dissemination.

Introduction: Tumor budding was declared as independent prognostic factor for early cancer in 2016. Tumor-associated fibroblasts (CAFs) are one of the main components of tumor microenvironment. Plenty of different markers are used for detection of CAFs, including podoplanin (POD)., Objective: The aim of this study is to identify correlation between tumor budding, that indicates tumor invasive potential and is considered to be a negative prognostic factor, and CAFs near tumor buds using POD., Material and Methods: 43 cases of colon adenocarcinoma are included in the study. Double staining immunohistochemical technology with PCK and POD was used for detection of tumor budding and evaluation of POD expression near tumor buds., Results: Significant correlations are revealed between tumor budding and depth of tumor invasion ( p =0.023)/regional lymph node metastasis ( p =0.068), but between POD expression and depth of tumor invasion ( p =0.088) only a tendency of correlation is identified. These facts demonstrate critical prognostic value of tumor budding instead POD expression near tumor buds. It was found that intensity of POD expression near tumor buds is statistically analogous to POD expression in the invasive margin ( p =0.0016). That means it is not necessary to evaluate POD expression exactly near tumor buds. For the first time stronger POD expression near mucin complexes is reported. That, probably, will allow to use mucin complexes as alternative prognostic factor instead tumor budding, as tumor buds are absent in mucinous adenocarcinoma.

Carcinogenesis and tumor progression are not caused not only by malignant epithelial cells, but also by the tumor stroma around cancer stem cells which performs regulatory, nutritional and 'framework' functions. It is represented by mesenchymal cells of various types predominantly by cancer-associated fibroblasts (CAF). αSMA, FAP-1, desmin, podoplanin, neuron-glial antigen 2 (NG2), PDGFR-α and -β are used for CAF identification but there is no universal markers due to the plasticity of the cell population that underlies the subpopulation division CAF. CAF subpopulations are not described for many tumor types. Recently, evidence has accumulated that CAFs mediate many adverse processes in the tumor, including can support stromal inflammation and cause fibrosis. By forming a niche in cancer stem cells, CAFs mediate chemoresistance and the appearance of dormant metastases. The study of the role of CAF will allow not only to form a fundamentally new understanding of the mechanisms of carcinogenesis, but also to create new diagnostic and therapeutic targets for treating tumors.

Objective: To study the relationship of LMP-1 expression with the clinical and morphological characteristics of gastric cancer and to study LMP-1 expression in the glandular epithelium of the peritumoral tissue., Material and Methods: Samples of gastric cancer surgical material from 67 patients were included in this study. Primary mouse monoclonal antibodies to LMP-1 protein were used. LMP-1 expression was considered as positive if at least in one of the selected 10 fields of view (lens magn. ×40) ratio of the number of cells with LMP-1 expression to the total number of cells exceeded 10%., Results: Nine cases of LMP-1 positive tumors, 32 cases of LMP-1 negative tumors and 26 cases of LMP-1-negative tumors with LMP-1-expression in the epithelium of the peritumoral tissue were detected. Last group was described for the first time; 4 of these were intestinal type tumors, 19 tumors were 'intermediate' type and 3 tumors were diffuse type, the prevalence of 'intermediate' type tumors was statistically significant., Conclusion: LMP-1-negative tumors with LMP-1-expression in the epithelium of the peritumoral tissue were identified and described for the first time. This group was predominantly represented by tumors of an 'intermediate' histological type of gastric cancer. EBV antigens may have any direct oncogenic effects, or play the role of the background or the concomitant processes. No significant relationship was found between the LMP-1 expression and depth of invasion (T), lymph nodes metastasis (N), distant metastasis (M), clinical stages. This fact can be explained by the high heterogeneity of molecular and genetic properties of gastric cancer.

EBV-associated gastric adenocarcinoma accounts for 10% of all gastric adenocarcinomas. The main known facts about the pathogenesis of EBV-associated gastric adenocarcinoma are presented. There are two main morphological types: gastric carcinoma with lymphoid stroma - GCLS (including lymphoepithelioma-like carcinoma; carcinoma with Crohn's disease-like lymphoid reaction; EBV-associated carcinoma with osteoclast-like giant cells) and conventional type adenocarcinoma. EBV-associated gastric adenocarcinomas predominantly express markers of gastric differentiation (MUC5AC, MUC6, CLDN-18) and a number of viral markers (EBER-1, EBNA-1 and BART mRNA). Three types of EBV latent cycle depending on the set of expressed viral transcripts are distinguished. It is believed that EBV-associated gastric adenocarcinoma is characterized by an intermediate position between latent cycles of types 1 and 2. The main method of virus identification is in situ hybridization with the detection of Epstein-Barr virus-encoded small RNAs (EBER-ISH).

The synthesis, composition, and catalytic properties of a new family of hexanuclear Cu(II)-based phenylsilsesquioxanes are described here. Structural studies of 17 synthesized compounds revealed the general principle underlying their molecular topology: viz., a central metal oxide layer consisting of two Cu 3 trimers is coordinated by two cyclic [PhSiO 1.5 ] 5 siloxanolate ligands to form a skewed sandwich architecture with the composition [(PhSiO 1.5 ) 10 (CuO) 6 ] 2+ . In addition to this O ligation by the siloxanolate rings, two opposite copper ions are additionally coordinated by the nitrogen atoms of corresponding N ligand(s), such as 2,2'-bipyridine (compounds 1-9), 1,10-phenanthroline (compounds 10-13), mixed 1,10-phenanthroline/2,2'-bipyridine (compound 14), or bathophenanthroline (compounds 15-17). Finally, the charge balance is maintained by two HO - (compounds 1-7, 10-13, and 15-17), two H 3 CO - (compound 8), or two CH 3 COO - (compounds 9 and 14) anions. Complexes 1 and 10 exhibited a high activity in the oxidative amidation oxidation of alcohols. Compounds 1, 10, and 15 are very efficient homogeneous catalysts in the oxidation of alkanes and alcohols with peroxides.

The synthesis, linear photophysical characterization, and nonlinear optical properties of two new symmetrical fluorene-containing quinolizinium derivatives, 2,8-bis((E)-2-(7-(diphenylamino)-9,9-dihexyl-9H-fluoren-2-yl)vinyl)quinolizinium hexafluorophosphate (1) and 2,8-bis((E)-2-(7-((7-(diphenylamino)-9,9-dihexyl-9H-fluoren-2-yl)ethynyl)-9,9-dihexyl-9H-fluoren-2yl)vinyl)quinolizinium hexafluorophosphate (2), are reported. The nature of the dual-band steady-state fluorescence emission of 1 and 2 was determined, and violation of Kasha's rule along with a strong dependence on solvent polarity were shown. A relatively complex structure of two-photon absorption (2PA) spectra of 1 and 2, with maximum cross sections of ∼400-600 GM, was determined using the open aperture Z-scan method. Different types of fast relaxation processes with characteristic times of 0.3-0.5 ps and 1.5-2 ps were observed in the excited states of the new compounds via femtosecond transient absorption pump-probe spectroscopy. To better understand the photophysical behavior of 1 and 2, a quantum-mechanical study was undertaken using TD-DFT and ZINDO/S methods. Simulated linear absorption spectra were found to be in good agreement with experimental data, while 2PA cross sections were overestimated. Although the new dyes were highly fluorescent in nonpolar solvents, they were essentially nonfluorescent in polar media. Significantly, the quinolizinium dyes exhibited fluorescence turn-on behavior upon binding to bovine serum album (BSA) protein, exhibiting over 4-fold fluorescence enhancement, which was a finding that was leveraged to demonstrate cell membrane fluorescence imaging of HeLa cells.

The synthesis, linear photophysical, two-photon absorption (2PA), femtosecond transient absorption, and superfluorescence properties of a new symmetrical squaraine derivative (1) are reported. Steady-state linear spectral and photochemical properties, fluorescence lifetimes, and excitation anisotropy of 1 were investigated in various organic solvents. High fluorescence quantum yields (≈0.7) and very high photostability (photodecomposition quantum yields ≈10(-6)-10(-8)) were observed. An open-aperture Z-scan method was used to obtain 2PA spectra of 1 over a broad spectral range (maximum 2PA cross section ≈1000 GM). Excited-state absorption (ESA) and gain was observed by femtosecond transient absorption spectroscopy, in which both reached a maximum at approximately 500 fs. Squaraine 1 exhibits efficient superfluorescence. The quantum chemical study of 1 revealed the simulated vibronic nature of the 1PA and 2PA spectra were in good agreement with experimental data; this may provide the ability to predict potential advanced photonic materials., (Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Efficient reversible phototransformation of a new diarylethene-fluorene derivative, 1,2-bis(5-(9,9-didecyl-7-nitro-9H-fluoren-2-yl)-2-methylthiophen-3-yl)cyclopent-1-ene (1), was demonstrated in organic media under low-intensity laser excitation. Linear photophysical characterization of 1 was performed at room temperature in solvents of different polarity and viscosity. Significantly, close to unity quantum yield for the cyclization reaction of 1 was shown in nonpolar solutions. The lifetimes of the excited states of the open (OF) and closed (CF) forms of 1 were measured by a femtosecond transient absorption technique, and corresponding values of ∼0.7 and ∼0.9 ps were shown in dichloromethane (DCM), respectively. Degenerate two-photon absorption (2PA) spectra of the OF and CF of 1 were obtained over a broad spectral range by the open aperture Z-scan method under 1 kHz femtosecond excitation. The values of 2PA cross sections of the OF in DCM (∼50-70 GM) were found to increase up to 1 order of magnitude (∼600 GM) after cyclization to the CF. The nature of cyclization and cylcoreversion processes were investigated by quantum chemistry with employment of DFT-based methods implemented in the Gaussian'09 program. The potential of 1 for application in optical data storage was shown using poly(methyl methacrylate)-doped films and two-photon fluorescence microscopy readout.

The photophysical, photochemical, two-photon absorption (2PA) and metal ion sensing properties of a new fluorene derivative (E)-1-(7-(4-(benzo[d]thiazol-2-yl)styryl)-9,9-bis(2-(2-ethoxyethoxy)ethyl)-9H-fluoren-2-yl)-3-(2-(9,10,16,17,18,19,21,22,23,24-decahydro-6H dibenzo[h,s][1,4,7,11,14,17]trioxatriazacycloicosin-20(7H)-yl)ethyl)thiourea (1) were investigated in organic and aqueous media. High sensitivity and selectivity of 1 to Zn(2+) in tetrahydrofuran and a water/acetonitrile mixture were shown by both absorption and fluorescence titration. The observed complexation processes corresponded to 1:1 stoichiometry with the range of binding constants approximately (2-3) x 10(5) M(-1). The degenerate 2PA spectra of 1 and 1/Zn(2+) complex were obtained in the 640-900 nm spectral range with the maximum values of two-photon action cross section for ligand/metal complex approximately (90-130) GM, using a standard two-photon induced fluorescence methodology under femtosecond excitation. The nature of the 2PA bands was analyzed by quantum chemical methods and a specific dependence on metal ion binding processes was shown. Ratiometric fluorescence detection (420/650 nm) provided a good dynamic range (10(-4) to 10(-6) M) for detecting Zn(2+), which along with the good photostability and 2PA properties of probe 1 makes it a good candidate in two-photon fluorescence microscopy imaging and sensing of Zn ions.

We report density functional theory (DFT) calculations of the Raman spectra for hexapeptides of glutamic acid and lysine in three different conformations (alpha, beta and PPII). The wave numbers of amide I, amide II and amide III bands of all three conformations predicted at B3LYP/6-31G and B3LYP/6-31G* are in good agreement with previously reported experimental values of polyglutamic acid and polylysine. Agreement with experiment improves when polarization functions are included in the basis set. Explicit water molecules, H-bonded to the backbone amide groups were found to be absolutely necessary to obtain this agreement. Our results indicate that DFT is a promising tool for assignment of the spectral data on kinetics of conformational changes for peptides during amyloid formation.

Conjugated organic molecules with photochromic properties are being extensively studied as prospective optical switching and data storage materials. Among different photochromic compounds, diarylethenes demonstrate thermal stability, fatigue resistance, and high quantum yield. The mechanism of photoswitching in diarylethenes involves a symmetry-allowed conrotatory electrocyclic reaction, initiated by UV light. Replacement of one UV photon with two near-IR ones would offer a number of practical advantages, including drastic increase in storage capacity via three-dimensional multilayer design. For this purpose we designed a prototype molecule with a two-photon absorbing (2PA) pendant substituent, attached to the photochromic diarylethene moiety. However, this molecule was experimentally shown to have lost the photoswitching properties. We analyze reasons for this loss using quantum chemistry tools. Analysis of the nodal structure of the frontier Kohn-Sham orbitals, allowed us to trace the route of the problem to the lone pair orbital of the 2PA substituent falling within the HOMO-LUMO (highest occupied molecular orbital-lowest unoccupied molecular orbital) gap of the photoreactive diarylethene moiety. We suggest a chemical modification of the 2PA substituent in order to restore the order of the orbitals. Potential energy plots along the reaction coordinate at the M05-2X/6-31G* theory level for the prototype 2PA photochromic molecule before and after the modification confirm the predictive capability of the proposed orbital approach. The Slater transition state method was used to obtain geometries along the reaction pathway by the constrained optimization of excited states, whereas potential energy curves were plotted using the recently proposed (Mikhailov, I. A.; Tafur, S.; Masunov, A. E. Phys. Rev. A 2008, 77 (1), 012510) a posteriori Tamm-Dancoff approximation to the time-dependent density functional theory in second order of the external field. We show that this combination is able to produce accurate potential surfaces for 1B and 2A excited states, as compared to available experimental data and results of high-level multireference wave function theory methods.