Theoretical study on an intriguing excited-state proton transfer process induced by weakened intramolecular hydrogen bonds.

In the present work, we have systematically investigated the dual hydrogen-bonded system 2Z,2'Z-3,3'-(4,4'-methylenebis(4,1-phenylene)bis(azanediyl)bis(1,3-diphenylprop-2-en-1-one)) (abbreviated as L) utilizing quantum chemistry methods, in which the excited-state intramolecular proton transfer (ESIPT) does not conform to the usual stereotype but proceeds along the weakened intramolecular hydrogen bonds (IHBs). Two primary configurations were confirmed to coexist in the ground state (i.e., anti-L and syn-L) by calculating the Boltzmann distribution in three different solvents. Based on the cardinal geometrical parameters involved in IHBs and the interaction region indicator (IRI) isosurface, it can be revealed that the dual IHBs of L were both weakened upon photoexcitation, not least the N1-H2⋯O3 IHB was utterly destroyed in the excited state. The proton-transfer process of anti and syn in three solvents with different polarities has been analyzed by constructing S0- and S1-state potential energy surfaces (PESs). It can be concluded that only the single proton transfer behavior along N1-H2⋯O3 occurs in the S1 state, and the corresponding energy barrier is gradually enlarged with increasing solvent polarity. To further expound the weakened IHB-induced ESIPT mechanism, the scanned PESs connecting the transition state (TS) structures and the initial forms indicate that the ESIPT process is infeasible without the appropriate structural torsion. Our work not only unveils the extraordinary ESIPT process of L, but also complements the results obtained from previous experiments.

Theoretical Investigation on the ESIPT Process and Detection Mechanism for Dual-Proton Type Fluorescent Probe.

Recently, a new fluorescent probe AE-Phoswas reported to detect the activity of alkaline phosphatases (ALP) in different living cell lines. Here, we present an in-depth computational analysis of the mechanism and source of the fluorescence of the AE-Phos probe. There is an intermediate product (AE-OH-Phos) in the experiment as well as a different configuration of products that may emit fluorescence. It is essential to investigate the origin of fluorescence and the detection mechanism of the probe, which could help us eliminate the interference of other substances (including an intermediate product and possible isomers) on fluorescence during the experiment. According to the change of geometric parameters and Infrared spectra, we deduce that the dual intramolecular hydrogen bonds of salicylaldehyde azine (SA) were enhanced at the excited state, while AE-OH-Phos was attenuated. Considering the complex ESIPT behavior of the dual proton-type probe, the potential energy surfaces were further discussed. It can be concluded that the single proton transfer structure of SA (SA-SPT) is the most stable form. Both the concerted double proton transfer process and stepwise single proton transfer process of SA were forbidden. The fluorescence for SA was 438 nm, while that of SA-SPT was 521 nm, which agrees with the experimentally measured fluorescence wavelength (536 nm). The conclusion that single proton transfer occurs in SA is once again verified. In addition, the distribution of electron-hole and relative index was analyzed to investigate the intrinsic mechanism for the fluorescence quenching of the probe and the intermediate product. The identification of the origin of fluorescence sheds light on the design and use of dual-proton type fluorescent probes in the future.

Overexpression of ABCC3 promotes cell proliferation, drug resistance, and aerobic glycolysis and is associated with poor prognosis in urinary bladder cancer patients.

Human urinary bladder cancer (UBC) is the one of the most common malignancies worldwide and occurs at a higher frequency in male individuals. ATP-binding cassette, subfamily C, member 3 (ABCC3), a member of the ABC transporter family, is highly expressed in tumor cells, where it actively effluxes a broad spectrum of metabolites. However, the expression and role of ABCC3 in human UBC remains unclear. Our study aimed to identify the expression status of ABCC3 in UBC cases and investigate the biological effects on UBC in cells. We found that both mRNA and protein levels of ABCC3 were significantly higher in UBC tissues than normal tissues. Immunochemistry evaluation of ABCC3 expression in 122 UBC clinical specimens showed that high expression of ABCC3 had a positive correlation with UBC tumor size, advanced tumor node metastasis stage, and malignant histology. Moreover, high ABCC3 expression was linked to poor overall survival in UBC. ABCC3 effects on cell proliferation and drug resistance were measured by colony formation and methylthiazolyldiphenyl-tetrazolium bromide (MTT) assays. ABCC3-knockdown cells showed a significant decrease in cell growth and drug resistance. RNA interference of ABCC3 also caused downregulation of lactate dehydrogenase A (LDHA), which positively correlated with ABCC3 expression in UBC specimens. In addition, cancer cell glycolytic ability was decreased upon ABCC3 knockdown. The activity of LDHA was also abrogated in ABCC3-deficient UBC cells, and the blockade of LDHA increased UBC cells sensitivity to Cis-diamine dichloroplatinum (CDDP). In summary, our study suggests ABCC3 is an important oncoprotein involved in glycolysis and drug resistance. These data also indicates that ABCC3 could be a potential prognostic marker and promising therapeutic target in UBC.

Attention-guided multi-scale context aggregation network for multi-modal brain glioma segmentation.

BACKGROUND: Accurate segmentation of brain glioma is a critical prerequisite for clinical diagnosis, surgical planning and treatment evaluation. In current clinical workflow, physicians typically perform delineation of brain tumor subregions slice-by-slice, which is more susceptible to variabilities in raters and also time-consuming. Besides, even though convolutional neural networks (CNNs) are driving progress, the performance of standard models still have some room for further improvement. PURPOSE: To deal with these issues, this paper proposes an attention-guided multi-scale context aggregation network (AMCA-Net) for the accurate segmentation of brain glioma in the magnetic resonance imaging (MRI) images with multi-modalities. METHODS: AMCA-Net extracts the multi-scale features from the MRI images and fuses the extracted discriminative features via a self-attention mechanism for brain glioma segmentation. The extraction is performed via a series of down-sampling, convolution layers, and the global context information guidance (GCIG) modules are developed to fuse the features extracted for contextual features. At the end of the down-sampling, a multi-scale fusion (MSF) module is designed to exploit and combine all the extracted multi-scale features. Each of the GCIG and MSF modules contain a channel attention (CA) module that can adaptively calibrate feature responses and emphasize the most relevant features. Finally, multiple predictions with different resolutions are fused through different weightings given by a multi-resolution adaptation (MRA) module instead of the use of averaging or max-pooling to improve the final segmentation results. RESULTS: Datasets used in this paper are publicly accessible, that is, the Multimodal Brain Tumor Segmentation Challenges 2018 (BraTS2018) and 2019 (BraTS2019). BraTS2018 contains 285 patient cases and BraTS2019 contains 335 cases. Simulations show that the AMCA-Net has better or comparable performance against that of the other state-of-the-art models. In terms of the Dice score and Hausdorff 95 for the BraTS2018 dataset, 90.4% and 10.2 mm for the whole tumor region (WT), 83.9% and 7.4 mm for the tumor core region (TC), 80.2% and 4.3 mm for the enhancing tumor region (ET), whereas the Dice score and Hausdorff 95 for the BraTS2019 dataset, 91.0% and 10.7 mm for the WT, 84.2% and 8.4 mm for the TC, 80.1% and 4.8 mm for the ET. CONCLUSIONS: The proposed AMCA-Net performs comparably well in comparison to several state-of-the-art neural net models in identifying the areas involving the peritumoral edema, enhancing tumor, and necrotic and non-enhancing tumor core of brain glioma, which has great potential for clinical practice. In future research, we will further explore the feasibility of applying AMCA-Net to other similar segmentation tasks.

Unveiling the influence of atomic electronegativity on the double ESIPT processes of uralenol: A theoretical study.

In this work, the effects of atomic electronegativity (O, S, and Se atoms) on the competitive double excited-state intramolecular proton transfer (ESIPT) reactions and photophysical characteristics of uralenol (URA) were systematically explored by using the density functional theory (DFT) and time-dependent DFT (TD-DFT) methods. The calculated hydrogen bond parameters, infrared (IR) vibrational spectra, reduced density gradient (RDG) scatter plots, interaction region indicator (IRI) isosurface and topology parameters have confirmed the six-membered intramolecular hydrogen bond (IHB) O4H5…O3 is the stronger one in all the three studied compounds. Subsequently, frontier molecular orbitals (FMOs) and natural bond orbital (NBO) population analysis essentially uncover that the electron redistribution has induced the ESIPT process. Besides, the constructed potential energy curves (PECs) have indicated that the ESIPT process prefers to occur along the O4H5…O3 rather than the O1H2…O3 and the proton-transfer energy barrier is gradually decreased with the weakening of atomic electronegativity from URA to URA-S and URA-Se. In a conclusion, the attenuating of atomic electronegativity has enhanced the IHBs of URA and thereby promoting the ESIPT reaction, which is helpful for further developing novel fluorophores based on ESIPT behavior in the future.

Substituent derivatives of benzothiazole-based fluorescence probes for hydrazine with conspicuous luminescence properties: A theoretical study.

In the present work, four probe molecules for detecting hydrazine have been designed based on the 2-(4-Acetoxy-3-benzothiazole-2-yl-phenyl)-4-methyl-thiazole- 5-carboxylic acid ethyl ester (HP1) to investigate the influence of the amino and cyano groups on the excited-state intramolecular proton transfer (ESIPT) behavior and photophysical properties. The changes in hydrogen bond strength indicate that the intramolecular hydrogen bond of all probe products is enhanced upon photoexcitation. Frontier molecular orbitals (FMOs) and natural bond orbital (NBO) reveal the driving force of ESIPT. In addition, the potential energy curves and transition state theory explain the reason for the single fluorescence phenomenon in the experiment. The simulated absorption and fluorescence spectra of HP1 and its product (HPP1) are completely consistent with the experimental results, which also verify the viewpoint. Meanwhile the cyano derivative HPP4 exhibits a larger Stokes-shift (201 nm) than that of HPP1 (145 nm) and has the same low energy barrier as HPP1. These excellent properties allow HPP4 to be a fluorescent probe with superior performance than the original molecule. In conclusion, this work can provide a theoretical basis for the design and synthesis of more sensitive fluorescent probes for the detection of hydrazine.

A DFT/TD-DFT Study on the ESIPT-Type Flavonoid Derivatives with High Emission Intensity.

To reveal the influence of different substituents on the excited-state intramolecular proton transfer (ESIPT) process and photophysical properties of 4'-N, N-dimethylamino-3-hydroxyflavone (DMA3HF), two novel molecules (DMA3HF-CN and DMA3HF-NH2) were designed by introducing the classical electron-withdrawing group cyano (-CN) and electron-donating group amino (-NH2). The three molecules in the acetonitrile phase were systematically researched by applying the density functional theory (DFT) and time-dependent DFT (TD-DFT) methods. The excited-state hydrogen bond enhancement mechanism was confirmed, and the hydrogen bond intensity followed the decreasing order of DMA3HF-NH2 > DMA3HF > DMA3HF-CN, which can be explained at the electronic level by natural bond orbital, fuzzy bond order, and frontier molecular orbital analyses. Moreover, we found from the electronic spectra that the fluorescence intensity of the three molecules in keto form is relatively strong. Moreover, the calculated absorption properties indicated that introducing the electron-withdrawing group -CN could significantly improve the absorption of DMA3HF in the ultraviolet band. In summary, the introduction of an electron-donating group -NH2 can promote the ESIPT reaction of DMA3HF, without changing the photophysical properties, while introducing the electron-withdrawing group -CN can greatly improve the absorption of DMA3HF in the ultraviolet band, but hinders the occurrence of the ESIPT reaction.

Insights into the photophysical properties of 2-(2'-hydroxyphenyl) benzazoles derivatives: Application of ESIPT mechanism on UV absorbers.

In this present work, four novel molecules (BPN, BPNS, BPS, and BPSN), possessing excited-state intramolecular proton transfer (ESIPT) characteristics, were designed to quantify the impacts of substituent effects on their photophysical properties. By exploring the primary geometrical parameters concerning hydrogen bonds, it should be noticed that the intramolecular hydrogen bonds (IHBs) of the studied molecules have been strengthened at S1 state. Infrared vibrational spectra analysis illustrates that adding electron-donating group thiophene to the proton donor side can weaken the IHBs in comparison to the electron-withdrawing group pyridine. Through investigating the absorption and fluorescence spectra, it can be clearly found that the maximum absorption peaks of the studied molecules are all located in the UVA region, and their regions of fluorescence peaks are harmless to human skin. Furthermore, considering the light intensity factor, it can be concluded that BPNS is the most potential to be used as UV absorbers in the studied molecules. This work investigates the effects of the positions and types of substituent groups on photophysical properties of 2-(2'-hydroxyphenyl) benzazoles derivatives, which can help design and exploit novel UV absorbers.

Theoretical Study on the Atom-Substituted Quinazoline Derivatives with Faint Emission as Potential Sunscreens.

Two novel compounds (HQS and HQSe) with excited-state intramolecular proton transfer (ESIPT) properties were designed based on the compound 2-(2-hydroxy-3-ethoxyphenyl)-3H-quinazolin-4-one (HQ). The parameters related to the ESIPT properties and electronic spectra of HQ and its derivatives were calculated using density functional theory and time-dependent density functional theory methods. The obtained geometric configurations, infrared vibrational spectra, and reduced density gradient scatter plots have shown that the intramolecular hydrogen bond O1···H1-N1 has been weakened upon photoexcitation. Moreover, from the scanned potential energy curves, it can be found that the ESIPT processes of the three compounds have no energy barriers. It is noteworthy that HQS and HQSe can strongly absorb light in the UVA region (∼340 nm) and exhibit weak fluorescence emission in the visible light region, which comes from the keto configuration. The special optical properties of HQS and HQSe can promote their application as potential sunscreen agents.

Tactfully unveiling the effect of solvent polarity on the ESIPT mechanism and photophysical property of the 3-hydroxylflavone derivative.

In this contribution, the solvent effects on the excited-state intramolecular proton transfer (ESIPT) and photophysical properties of 2-(4-(diphenylamine)phenyl)-3-hydroxy-4H-chromen-4-one (3HF-OH, Dyes Pigm. 2021, 184, 108865) in the dimethylsulfoxide (DMSO), acetonitrile (ACN), dichloromethane (DCM) and cyclohexane (CYH) phases have been comprehensively explored by using the density functional theory (DFT) and time-dependent density functional theory (TD-DFT) methods. The obtained bond lengths, bond angles and infrared (IR) vibration analysis related to the intramolecular hydrogen bond (IHB) reveal that the IHB intensity of 3HF-OH is weakened as the solvent polarity increased. Besides, the ESIPT process changes from the endothermic to the exothermic with the enlargement of solvent polarity, and the reaction barrier increases gradually. It is worth noting that the molecular configuration torsion of 3HF-OH is gradually intensified with the decline of solvent polarity, which aggravates the twisted intramolecular charge transfer (TICT) state and thereby partially attenuates the short-wavelength fluorescence of 3HF-OH in the CYH solvent. In addition to these, the structural torsion has restrained the occurrence of the ESIPT behavior by means of elevating the energy barrier. This theoretical research would provide valuable guidance for regulating and controlling the photophysical behavior of compounds via the strategy of changing solvent polarity.