Excited States and Photodebromination of Selected Polybrominated Diphenyl Ethers: Computational and Quantitative Structure—Property Relationship Studies

This paper presents a density functional theory (DFT)/time-dependent DFT (TD-DFT) study on the lowest lying singlet and triplet excited states of 20 selected polybrominateddiphenyl ether (PBDE) congeners, with the solvation effect included in the calculations using the polarized continuum model (PCM). The results obtained showed that for most of the brominated diphenyl ether (BDE) congeners, the lowest singlet excited state was initiated by the electron transfer from HOMO to LUMO, involving a π–σ* excitation. In triplet excited states, structure of the BDE congeners differed notably from that of the BDE ground states with one of the specific C–Br bonds bending off the aromatic plane. In addition, the partial least squares regression (PLSR), principal component analysis-multiple linear regression analysis (PCA-MLR), and back propagation artificial neural network (BP-ANN) approaches were employed for a quantitative structure-property relationship (QSPR) study. Based on the previously reported kinetic data for the debromination by ultraviolet (UV) and sunlight, obtained QSPR models exhibited a reasonable evaluation of the photodebromination reactivity even when the BDE congeners had same degree of bromination, albeit different patterns of bromination.     

Evidence of the CH···O HydrogenBonding in Imidazolium-Based Ionic Liquids from Far-Infrared Spectroscopy Measurements and DFT Calculations

Knowledge of all the intermolecular forces occurring in ionic liquids (ILs) is essential to master their properties. Aiming at investigating the weaker hydrogen bonding in aprotic liquids, the present work combined computational study and far-infrared spectroscopy on four imidazolium-based ILs with different anions. The DFT calculations of the ionic couples, using the ωB97X-D functional and considering both the empirical dispersion corrections and the presence of a polar solvent, show that, for all samples, the lowest energy configurations of the ion pair present H atoms, directly bound to C atoms of the cation and close to O atoms of the anion, capable of creating moderate to weak hydrogen bonding with anions. For the liquids containing anions of higher bonding ability, the absorption curves generated from the calculated vibrational frequencies and intensities show absorption bands between 100 and 125 cm⁻¹ corresponding to the stretching of the hydrogen bond. These indications are in complete agreement with the presently reported temperature dependence of the far-infrared spectrum, where the stretching modes of the hydrogen bonding are detected only for samples presenting a moderate interaction and become particularly prominent at low temperatures. Moreover, from the analysis of the infrared spectra, the occurrence of various phase transitions as a function of temperature was detected, and the difference in the average energy between the H-bonded and the dispersion-governed molecular configurations was evaluated.     

Intramolecular Charge Transfer of Curcumin and Solvation Dynamics of DMSO Probed by Time-Resolved Raman Spectroscopy

Intramolecular charge transfer (ICT) of curcumin in dimethyl sulfoxide (DMSO) solution in the excited state was investigated by femtosecond electronic and vibrational spectroscopy. Excited-state Raman spectra of curcumin in the locally-excited and charge-transferred (CT) state of the S₁ excited state were separated due to high temporal (<50 fs) and spectral (<10 cm⁻¹) resolutions of femtosecond stimulated Raman spectroscopy. The ultrafast (0.6–0.8 ps) ICT and subsequent vibrational relaxation (6–9 ps) in the CT state were ubiquitously observed in the ground- and excited-state vibrational modes of the solute curcumin and the ν_CSC and ν_S=O modes of solvent DMSO. The ICT of curcumin in the excited state was preceded by the disruption of the solvation shells, including the breakage of hydrogen bonding between curcumin and DMSO molecules, which occurs at the ultrafast (20–50 fs) time scales.     

Excited States of Bromopyrimidines Probed by VUV Photoabsorption Spectroscopy and Theoretical Calculations

We report absolute photoabsorption cross sections for gas-phase 2- and 5-bromopyrimidine in the 3.7–10.8 eV energy range, in a joint theoretical and experimental study. The measurements were carried out using high-resolution vacuum ultraviolet synchrotron radiation, with quantum chemical calculations performed through the nuclear ensemble approach in combination with time-dependent density functional theory, along with additional Franck–Condon Herzberg–Teller calculations for the first absorption band (3.7–4.6 eV). The cross sections of both bromopyrimidines are very similar below 7.3 eV, deviating more substantially from each other at higher energies. In the 7.3–9.0 eV range where the maximum cross-section is found, a single and broad band is observed for 5-bromopyrimidine, while more discernible features appear in the case of 2-bromopyrimidine. Several π* ← π transitions account for the most intense bands, while weaker ones are assigned to transitions involving the nitrogen and bromine lone pairs, the antibonding σ*_Br orbital, and the lower-lying Rydberg states. A detailed comparison with the available photo-absorption data of bromobenzene is also reported. We have found significant differences regarding the main absorption band, which is more peaked in bromobenzene, becoming broader and shifting to higher energies in both bromopyrimidines. In addition, there is a significant suppression of vibrational structures and of Rydberg states in the pair of isomers, most noticeably for 2-bromopyrimidine.     

A TD-DFT Study on the Photo-Physicochemical Properties of Chrysophanol from Rheum

As a naturally occurring anthraquinone pigment, chrysophanol (MHAQ) has attracted considerable attention in recent years owing to its efficient photosensitivity under the solar spectrum. Considering the successful use of time-dependent density functional theory (TD-DFT) in investigating the photo-physicochemical behaviors of dyes and pigments, we performed a study by means of TD-DFT calculations, which provided us with various excited state properties of chrysophanol, including absorption spectrum, lowest triplet excited-state energy, vertical electron affinity and vertical ionization potential. On the basis of the calculated results, the photosensitive mechanisms of chrysophanol were discussed and some deeper insights were gained. First, we indicated that the experimentally observed chrysophanol’s photo-damage to DNA in oxygen-free media is more likely to arise from MHAQ^•+ rather than from T₁ state chrysophanol. Second, we revealed that it is the MHAQ^•− that is responsible for the O₂^•− generation in solvents. Based on the photosensitive activities, chrysophanol may be potentially used as the photodynamic medicine for clinical therapy of the diseases occurring on the shallow surface and vascular capillary diseases.     

Diets with Higher ω-6/ω-3 Ratios Show Differences in Ceramides and Fatty Acid Levels Accompanied by Increased Amyloid-Beta in the Brains of Male APP/PS1 Transgenic Mice

Senile plaque formation as a consequence of amyloid-β peptide (Aβ) aggregation constitutes one of the main hallmarks of Alzheimer’s disease (AD). This pathology is characterized by synaptic alterations and cognitive impairment. In order to either prevent or revert it, different therapeutic approaches have been proposed, and some of them are focused on diet modification. Modification of the ω-6/ω-3 fatty acids (FA) ratio in diets has been proven to affect Aβ production and senile plaque formation in the hippocampus and cortex of female transgenic (TG) mice. In these diets, linoleic acid is the main contribution of ω-6 FA, whereas alpha-linoleic acid (ALA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and docosapentaenoic acid (DPA) are the contributors of ω-3 FA. In the present work, we have explored the effect of ω-6/ω-3 ratio modifications in the diets of male double-transgenic APPswe/PS1ΔE9 (AD model) and wild-type mice (WT). Amyloid burden in the hippocampus increased in parallel with the increase in dietary ω-6/ω-3 ratio in TG male mice. In addition, there was a modification in the brain lipid profile proportional to the ω-6/ω-3 ratio of the diet. In particular, the higher the ω-6/ω-3 ratio, the lower the ceramides and higher the FAs, particularly docosatetraenoic acid. Modifications to the cortex lipid profile was mostly similar between TG and WT mice, except for gangliosides (higher levels in TG mice) and some ceramide species (lower levels in TG mice).     

Exploration of Diazaspiro Cores as Piperazine Bioisosteres in the Development of σ2 Receptor Ligands

A series of σ2R compounds containing benzimidazolone and diazacycloalkane cores was synthesized and evaluated in radioligand binding assays. Replacing the piperazine moiety in a lead compound with diazaspiroalkanes and the fused octahydropyrrolo[3,4-b] pyrrole ring system resulted in a loss in affinity for the σ2R. On the other hand, the bridged 2,5-diazabicyclo[2.2.1]heptane, 1,4-diazepine, and a 3-aminoazetidine analog possessed nanomolar affinities for the σ2R. Computational chemistry studies were also conducted with the recently published crystal structure of the σ2R/TMEM97 and revealed that hydrogen bond interactions with ASP29 and π-stacking interactions with TYR150 were largely responsible for the high binding affinity of small molecules to this protein.     

Omega-6 Polyunsaturated Fatty Acids Enhance Tumor Aggressiveness in Experimental Lung Cancer Model: Important Role of Oxylipins

Lung cancer is currently the leading cause of cancer death worldwide; it is often diagnosed at an advanced stage and bears poor prognosis. It has been shown that diet is an important environmental factor that contributes to the risk and mortality of several types of cancers. Intake of ω-3 and ω-6 PUFAs plays an important role in cancer risk and progression. Current Western populations have high consumption of ω-6 PUFAs with a ratio of ω-6/ω-3 PUFAs at 15:1 to 16.7:1 This high consumption of ω-6 PUFAs is related to increased cancer risk and progression. However, whether a diet rich in ω-6 PUFAs can contribute to tumor aggressiveness has not been well investigated. We used a murine model of pulmonary squamous cell carcinoma to study the aggressiveness of tumors in mice fed with a diet rich in ω-6 PUFAs and its relationship with oxylipins. Our results shown that the mice fed a diet rich in ω-6 showed a marked increase in proliferation, angiogenesis and pro-inflammatory markers and decreased expression of pro-apoptotic proteins in their tumors. Oxylipin profiling revealed an upregulation of various pro-tumoral oxylipins including PGs, HETEs, DiHETrEs and HODEs. These results demonstrate for the first time that high intake of ω-6 PUFAs in the diet enhances the malignancy of tumor cells by histological changes on tumor dedifferentiation and increases cell proliferation, angiogenesis, pro-inflammatory oxylipins and molecular aggressiveness targets such as NF-κB p65, YY1, COX-2 and TGF-β.     

Signatures of Conical Intersection Dynamics in the Time-Resolved Photoelectron Spectrum of Furan: Theoretical Modeling with an Ensemble Density Functional Theory Method

The non-adiabatic dynamics of furan excited in the ππ* state (S₂ in the Franck–Condon geometry) was studied using non-adiabatic molecular dynamics simulations in connection with an ensemble density functional method. The time-resolved photoelectron spectra were theoretically simulated in a wide range of electron binding energies that covered the valence as well as the core electrons. The dynamics of the decay (rise) of the photoelectron signal were compared with the excited-state population dynamics. It was observed that the photoelectron signal decay parameters at certain electron binding energies displayed a good correlation with the events occurring during the excited-state dynamics. Thus, the time profile of the photoelectron intensity of the K-shell electrons of oxygen (decay constant of 34 ± 3 fs) showed a reasonable correlation with the time of passage through conical intersections with the ground state (47 ± 2 fs). The ground-state recovery constant of the photoelectron signal (121 ± 30 fs) was in good agreement with the theoretically obtained excited-state lifetime (93 ± 9 fs), as well as with the experimentally estimated recovery time constant (ca. 110 fs). Hence, it is proposed to complement the traditional TRPES observations with the trXPS (or trNEXAFS) measurements to obtain more reliable estimates of the most mechanistically important events during the excited-state dynamics.     

VCD Studies on Chiral Characters of Metal Complex Oligomers

The present article reviews the results on the application of vibrational circular dichroism (VCD) spectroscopy to the study of stereochemical properties of chiral metal complexes in solution. The chiral characters reflecting on the vibrational properties of metal complexes are revealed by measurements of a series of β-diketonato complexes with the help of theoretical calculation. Attention is paid to the effects of electronic properties of a central metal ion on vibrational energy levels or low-lying electronic states. The investigation is further extended to the oligomers of β-diketonato complex units. The induction of chiral structures is confirmed by the VCD spectra when chiral inert moieties are connected with labile metal ions. These results have demonstrated how VCD spectroscopy is efficient in revealing the static and dynamic properties of mononuclear and multinuclear chiral metal complexes, which are difficult to clarify by means of other spectroscopes.     

Intramolecular Charge Transfer of 1-Aminoanthraquinone and Ultrafast Solvation Dynamics of Dimethylsulfoxide

The intramolecular charge transfer (ICT) of 1-aminoanthraquinone (AAQ) in the excited state strongly depends on its solvent properties, and the twisted geometry of its amino group has been recommended for the twisted ICT (TICT) state by recent theoretical works. We report the transient Raman spectra of AAQ in a dimethylsulfoxide (DMSO) solution by femtosecond stimulated Raman spectroscopy to provide clear experimental evidence for the TICT state of AAQ. The ultrafast (~110 fs) TICT dynamics of AAQ were observed from the major vibrational modes of AAQ including the ν_C-N + δ_CH and ν_C=O modes. The coherent oscillations in the vibrational bands of AAQ strongly coupled to the nuclear coordinate for the TICT process have been observed, which showed its anharmonic coupling to the low frequency out of the plane deformation modes. The vibrational mode of solvent DMSO, ν_S=O showed a decrease in intensity, especially in the hydrogen-bonded species of DMSO, which clearly shows that the solvation dynamics of DMSO, including hydrogen bonding, are crucial to understanding the reaction dynamics of AAQ with the ultrafast structural changes accompanying the TICT.     

Maternal PUFA ω-3 Supplementation Prevents Neonatal Lung Injuries Induced by Hyperoxia in Newborn Rats

Bronchopulmonary dysplasia (BPD) is one of the most common complications of prematurity, occurring in 30% of very low birth weight infants. The benefits of dietary intake of polyunsaturated fatty acids ω-3 (PUFA ω-3) during pregnancy or the perinatal period have been reported. The aim of this study was to assess the effects of maternal PUFA ω-3 supplementation on lung injuries in newborn rats exposed to prolonged hyperoxia. Pregnant female Wistar rats (n = 14) were fed a control diet (n = 2), a PUFA ω-6 diet (n = 6), or a PUFA ω-3 diet (n = 6), starting with the 14th gestation day. At Day 1, female and newborn rats (10 per female) were exposed to hyperoxia (O₂, n = 70) or to the ambient air (Air, n = 70). Six groups of newborns rats were obtained: PUFA ω-6/O₂ (n = 30), PUFA ω-6/air (n = 30), PUFA ω-3/O₂ (n = 30), PUFA ω-3/air (n = 30), control/O₂ (n = 10), and control/air (n = 10). After 10 days, lungs were removed for analysis of alveolarization and pulmonary vascular development. Survival rate was 100%. Hyperoxia reduced alveolarization and increased pulmonary vascular wall thickness in both control (n = 20) and PUFA ω-6 groups (n = 60). Maternal PUFA ω-3 supplementation prevented the decrease in alveolarization caused by hyperoxia (n = 30) compared to PUFA ω-6/O₂ (n = 30) or to the control/O₂ (n = 10), but did not significantly increase the thickness of the lung vascular wall. Therefore, maternal PUFA ω-3 supplementation may protect newborn rats from lung injuries induced by hyperoxia. In clinical settings, maternal PUFA ω-3 supplementation during pregnancy and during lactation may prevent BPD development after premature birth.     

Multi-Omic Profiling of Macrophages Treated with Phospholipids Containing Omega-3 and Omega-6 Fatty Acids Reveals Complex Immunomodulatory Adaptations at Protein,Lipid and Metabolic Levels

In recent years, several studies have demonstrated that polyunsaturated fatty acids have strong immunomodulatory properties, altering several functions of macrophages. In the present work, we sought to provide a multi-omic approach combining the analysis of the lipidome, the proteome, and the metabolome of RAW 264.7 macrophages supplemented with phospholipids containing omega-3 (PC 18:0/22:6; ω3-PC) or omega-6 (PC 18:0/20:4; ω6-PC) fatty acids, alone and in the presence of lipopolysaccharide (LPS). Supplementation of macrophages with ω3 and ω6 phospholipids plus LPS produced a significant reprogramming of the proteome of macrophages and amplified the immune response; it also promoted the expression of anti-inflammatory proteins (e.g., pleckstrin). Supplementation with the ω3-PC and ω6-PC induced significant changes in the lipidome, with a marked increase in lipid species linked to the inflammatory response, attributed to several pro-inflammatory signalling pathways (e.g., LPCs) but also to the pro-resolving effect of inflammation (e.g., PIs). Finally, the metabolomic analysis demonstrated that supplementation with ω3-PC and ω6-PC induced the expression of several metabolites with a pronounced inflammatory and anti-inflammatory effect (e.g., succinate). Overall, our data show that supplementation of macrophages with ω3-PC and ω6-PC effectively modulates the lipidome, proteome, and metabolome of these immune cells, affecting several metabolic pathways involved in the immune response that are triggered by inflammation.     

Quantum transport simulations of graphene nanoribbon devices using Dirac equation calibrated with tight-binding π-bond model

We present an efficient approach to study the carrier transport in graphene nanoribbon (GNR) devices using the non-equilibrium Green''s function approach (NEGF) based on the Dirac equation calibrated to the tight-binding π-bond model for graphene. The approach has the advantage of the computational efficiency of the Dirac equation and still captures sufficient quantitative details of the bandstructure from the tight-binding π-bond model for graphene. We demonstrate how the exact self-energies due to the leads can be calculated in the NEGF-Dirac model. We apply our approach to GNR systems of different widths subjecting to different potential profiles to characterize their device physics. Specifically, the validity and accuracy of our approach will be demonstrated by benchmarking the density of states and transmissions characteristics with that of the more expensive transport calculations for the tight-binding π-bond model.     

Transplantation of Brown Adipose Tissue with the Ability of Converting Omega-6 to Omega-3 Polyunsaturated Fatty Acids Counteracts High-Fat-Induced Metabolic Abnormalities in Mice

A balanced omega (ω)-6/ω-3 polyunsaturated fatty acids (PUFAs) ratio has been linked to metabolic health and the prevention of chronic diseases. Brown adipose tissue (BAT) specializes in energy expenditure and secretes signaling molecules that regulate metabolism via inter-organ crosstalk. Recent studies have uncovered that BAT produces different PUFA species and circulating oxylipin levels are correlated with BAT-mediated energy expenditure in mice and humans. However, the impact of BAT ω-6/ω-3 PUFAs on metabolic phenotype has not been fully elucidated. The Fat-1 transgenic mice can convert ω-6 to ω-3 PUFAs. Here, we demonstrated that mice receiving Fat-1 BAT transplants displayed better glucose tolerance and higher energy expenditure. Expression of genes involved in thermogenesis and nutrient utilization was increased in the endogenous BAT of mice receiving Fat-1 BAT, suggesting that the transplants may activate recipients’ BAT. Using targeted lipidomic analysis, we found that the levels of several ω-6 oxylipins were significantly reduced in the circulation of mice receiving Fat-1 BAT transplants than in mice with wild-type BAT transplants. The major altered oxylipins between the WT and Fat-1 BAT transplantation were ω-6 arachidonic acid-derived oxylipins via the lipoxygenase pathway. Taken together, these findings suggest an important role of BAT-derived oxylipins in combating obesity-related metabolic disorders.     

Resveratrol-Encapsulated Mitochondria-Targeting Liposome Enhances Mitochondrial Respiratory Capacity in Myocardial Cells

The development of drug delivery systems for use in the treatment of cardiovascular diseases is an area of great interest. We report herein on an evaluation of the therapeutic potential of a myocardial mitochondria-targeting liposome, a multifunctional envelope-type nano device for targeting pancreatic β cells (β-MEND) that was previously developed in our laboratory. Resveratrol (RES), a natural polyphenol compound that has a cardioprotective effect, was encapsulated in the β-MEND (β-MEND (RES)), and its efficacy was evaluated using rat myocardioblasts (H9c2 cells). The β-MEND (RES) was readily taken up by H9c2 cells, as verified by fluorescence-activated cell sorter data, and was observed to be colocalized with intracellular mitochondria by confocal laser scanning microscopy. Myocardial mitochondrial function was evaluated by a Seahorse XF Analyzer and the results showed that the β-MEND (RES) significantly activated cellular maximal respiratory capacity. In addition, the β-MEND (RES) showed no cellular toxicity for H9c2 cells as evidenced by Premix WST-1 assays. This is the first report of the use of a myocardial mitochondria-targeting liposome encapsulating RES for activating mitochondrial function, which was clearly confirmed based on analyses using a Seahorse XF Analyzer.     

Disentangling the Molecular Mechanisms of the Antidepressant Activity of Omega-3 Polyunsaturated Fatty Acid: A Comprehensive Review of the Literature

Major depressive disorders (MDDs) are often associated with a deficiency in long-chain omega-3 polyunsaturated fatty acids (ω-3 PUFAs), as well as signs of low-grade inflammation. Epidemiological and dietary studies suggest that a high intake of fish, the major source of ω-3 PUFAs, is associated with lower rates of MDDs. Meta-analyses of randomized placebo-controlled ω-3 PUFAs intervention-trials suggest that primarily eicosapentaenoic acid (EPA), but not docosahexaenoic acid (DHA), is responsible for the proposed antidepressant effect. In this review, we dissect the current biological knowledge on EPA and DHA and their bioactive lipid metabolites to search for a pharmacological explanation of this, to date, unexplained clinical observation. Through enzymatic conversion by cyclooxygenase (COX), lipoxygenase (ALOX), and cytochrome P-450 monooxygenase (CYP), EPA and DHA are metabolized to major anti-inflammatory and pro-resolving lipid mediators. In addition, both ω-3 PUFAs are precursors for endocannabinoids, with known effects on immunomodulation, neuroinflammation, food intake and mood. Finally, both ω-3 PUFAs are crucial for the structure and organization of membranes and lipid rafts. While most biological effects are shared by these two ω-3 PUFAs, some distinct features could be identified: (1) The preferential CYP monooxygenase pathway for EPA and EPA derived eicosanoids; (2) The high CB2 receptor affinities of EPA-derived EPEA and its epoxy-metabolite 17,18-EEQ-EA, while the DHA-derived endocannabinoids lack such receptor affinities; (3) The competition of EPA but not DHA with arachidonic acid (AA) for particular glycerophospholipids. EPA and AA are preferentially incorporated into phosphatidylinositols, while DHA is mainly incorporated into phosphatidyl-ethanolamine, -serine and -choline. We propose that these distinct features may explain the superior antidepressant activity of EPA rich ω-3 PUFAs and that these are potential novel targets for future antidepressant drugs.     

Structural Contour Map of the Iota Carbonic Anhydrase from the Diatom Thalassiosira pseudonana Using a Multiprong Approach

Carbonic anhydrases (CAs) are a family of ubiquitous enzymes that catalyze the interconversion of CO₂ and HCO₃⁻. The “iota” class (ι-CA) was first found in the marine diatom Thalassiosira pseudonana (tpι-CA) and is widespread among photosynthetic microalgae and prokaryotes. The ι-CA has a domain COG4875 (or COG4337) that can be repeated from one to several times and resembles a calcium–calmodulin protein kinase II association domain (CaMKII-AD). The crystal structure of this domain in the ι-CA from a cyanobacterium and a chlorarachniophyte has been recently determined. However, the three-dimensional organization of the four domain-containing tpι-CA is unknown. Using biophysical techniques and 3-D modeling, we show that the homotetrameric tpι-CA in solution has a flat “drone-like” shape with a core formed by the association of the first two domains of each monomer, and four protruding arms formed by domains 3 and 4. We also observe that the short linker between domains 3 and 4 in each monomer confers high flexibility, allowing for different conformations to be adopted. We propose the possible 3-D structure of a truncated tpι-CA containing fewer domain repeats using experimental data and discuss the implications of this atypical shape on the activity and metal coordination of the ι-CA.     

Glycyrrhizin Attenuates Carcinogenesis by Inhibiting the Inflammatory Response in a Murine Model of Colorectal Cancer

Glycyrrhizin (GL), an important active ingredient of licorice root, which weakens the proinflammatory effects of high-mobility group box 1 (HMGB1) by blocking HMGB1 signaling. In this study, we investigated whether GL could suppress inflammation and carcinogenesis in an azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced murine model of colorectal cancer. ICR mice were divided into four groups (n = 5, each)—control group, GL group, colon cancer (CC) group, and GL-treated CC (CC + GL) group, and sacrificed after 20 weeks. Plasma levels of interleukin (IL)-6 and tumor necrosis factor (TNF)-α were measured using an enzyme-linked immunosorbent assay. The colonic tissue samples were immunohistochemically stained with DNA damage markers (8-nitroguanine and 8-oxo-7,8-dihydro-2′-deoxy-guanosine), inflammatory markers (COX-2 and HMGB1), and stem cell markers (YAP1 and SOX9). The average number of colonic tumors and the levels of IL-6 and TNF-α in the CC + GL group were significantly lower than those in the CC group. The levels of all inflammatory and cancer markers were significantly reduced in the CC + GL group. These results suggest that GL inhibits the inflammatory response by binding HMGB1, thereby inhibiting DNA damage and cancer stem cell proliferation and dedifferentiation. In conclusion, GL significantly attenuates the pathogenesis of AOM/DSS-induced colorectal cancer by inhibiting HMGB1-TLR4-NF-κB signaling.     

Strong Hydrogen Bonds in Acetylenedicarboxylic Acid Dihydrate

Acetylenedicarboxylic acid dihydrate (ADAD) represents a complex with strong hydrogen bonding between the carboxylic OH and the water molecule. An X-ray re-examination of the ADAD crystal structure confirms the O^…O distance of the short hydrogen bonds, and clearly shows different bond lengths between the two oxygen atoms with respect to the carbon atom in the carboxyl group, indicating a neutral structure for the complex. The neutral structure was also confirmed by vibrational spectroscopy, as no proton transfer was observed. The diffraction studies also revealed two polymorph modifications: room temperature (α) and low temperature (β), with a phase transition at approximately 4.9 °C. The calculated vibrational spectra are in satisfactory agreement with the experimental spectra. A comparison of the structure and the vibrational spectra between the ADAD and the oxalic acid dihydrate reveals some interesting details. The crystal structures of both crystal hydrates are almost identical; only the O^…O distances of the strongest hydrogen bonds differ by 0.08 Å. Although it was expected that a larger O^…O spacing in the ADAD crystal may significantly change the infrared and Raman spectra, especially for the frequency and the shape of the acidic OH stretching vibration, both the shape and frequency are almost identical, with all subpeaks topped on the broad OH stretching vibration. The O^…O distance dependent are only in- and out-of-plane OH deformations modes. The presence of polarons due to the ionized defects was not observed in the vibrational spectra of ADAD. Therefore, the origin of the broad OH band shape was explained in a similar way to the acid dimers. The anharmonicity of a potential enhances the coupling of the OH stretching with the low-frequency hydrogen bond stretching, which, in addition to the Fermi resonance, structures the band shape of the OH stretching. The fine structure found as a superposition of a broad OH stretching is attributed to Davydov coupling.