Cinnamic Acid: A Low-Toxicity Natural Bidentate Ligand for Uranium Decorporation.

Uranium accumulation in the kidneys and bones following internal contamination results in severe damage, emphasizing the pressing need for the discovery of actinide decorporation agents with efficient removal of uranium and low toxicity. In this work, cinnamic acid (3-phenyl-2-propenoic acid, CD), a natural aromatic carboxylic acid, is investigated as a potential uranium decorporation ligand. CD demonstrates markedly lower cytotoxicity than that of diethylenetriaminepentaacetic acid (DTPA), an actinide decorporation agent approved by the FDA, and effectively removes approximately 44.5% of uranyl from NRK-52E cells. More importantly, the results of the prompt administration of the CD solution remove 48.2 and 27.3% of uranyl from the kidneys and femurs of mice, respectively. Assessments of serum renal function reveal the potential of CD to ameliorate uranyl-induced renal injury. Furthermore, the single crystal of CD and uranyl compound (C9H7O2)2·UO2 (denoted as UO2-CD) reveals the formation of uranyl dimers as secondary building units. Thermodynamic analysis of the solution shows that CD coordinates with uranyl to form a 2:1 molar ratio complex at a physiological pH of 7.4. Density functional theory (DFT) calculations further show that CD exhibits a significant 7-fold heightened affinity for uranyl binding in comparison to DTPA.

Antibacterial Photodynamic Therapy by Zn(II)-Curcumin Complex: Synthesis, Characterization, DFT Calculation, Antibacterial Activity, and Molecular Docking.

The increase in antibacterial drug resistance is threatening global health conditions. Recently, antibacterial photodynamic therapy (aPDT) has emerged as an effective antibacterial treatment with high cure gain. In this work, three Zn(II) complexes viz., [Zn(en)(acac)Cl] (1), [Zn(bpy)(acac)Cl] (2), [Zn(en)(cur)Cl] (3), where en=ethylenediamine (1 and 3), bpy=2,2'-bipyridine (2), acac=acetylacetonate (1 and 2), cur=curcumin monoanionic (3) were developed as aPDT agents. Complexes 1-3 were synthesized and fully characterized using NMR, HRMS, FTIR, UV-Vis. and fluorescence spectroscopy. The HOMO-LUMO energy gap (Eg), and adiabatic splittings (ΔS1-T1 and ΔS0-T1 ) obtained from DFT calculation indicated the photosensivity of the complexes. These complexes have not shown any potent antibacterial activity under dark conditions but the antibacterial activity of these complexes was significantly enhanced upon light exposure (MIC value up to 0.025 µg/mL) due to their light-mediated 1 O2 generation abilities. The molecular docking study suggested that complexes 1-3 interact efficiently with DNA gyrase B (PDB ID: 4uro). Importantly, 1-3 did not show any toxicity toward normal HEK-293 cells. Overall, in this work, we have demonstrated the promising potential of Zn(II) complexes as effective antibacterial agents under the influence of visible light.

A density functional theory study on how γ-Al2O3 - Boehmite transformation affects carbon evolution during aqueous-phase reaction.

Gamma-alumina (γ-Al2O3), one of the most common materials, is commercially used in many catalytic applications, including the active catalyst and support. However, the problem of fast deactivation makes the utilization of the γ-Al2O3 challenging. This work elucidates the mechanism of coke formation consisting of coke deposition and evolution on γ-Al2O3(110) surfaces in differential conditions, including; clean and hydroxylation γ-Al2O3(110) in terms of partial and fully hydroxylation of OH/γ-Al2O3(110) and AlOOH(010), respectively. We demonstrated that the γ-Al2O3(110) surface is proper for atomic coke deposition and dimerization in the initial state, where the presence of OH species promotes the coke evolution to higher coke, Cn (where n ≥ 3). Also, the higher coke formation thermodynamically preferred the cyclic form to the aliphatic one. The electron transfer from substrates to adsorbed coke illustrates the role of the electron donor of catalyst surfaces corresponding to the electron acceptor of adsorbed cokes.

Phytochemical investigation, molecular docking studies and DFT calculations on the antidiabetic and cytotoxic activities of Gmelina philippensis CHAM.

ETHNOPHARMACOLOGICAL RELEVANCE: Gmelina philippensis CHAM is an ornamental plant that is distributed in South Asia and warm regions of the Mediterranean area. The plant is traditionally applied in folk medicine for the treatment of diabetes. AIM OF THE STUDY: To evaluate the cytotoxic and the antidiabetic activities of the ethanolic extract of G. philippensis aerial parts. To isolate the metabolite(s) responsible for these activities and to elucidate the mechanism of action by molecular docking study. MATERIALS AND METHODS: Compounds (1-11) were isolated using various chromatographic techniques and their structures were determined by NMR spectroscopic and mass spectrometric analysis. The cytotoxic effect was tested using viability test and MTT assay. Antidiabetic activity was evaluated by measuring the inhibitory activity of the ethanolic extracts and compounds against α-glucosidase and α-amylase activities. Modeling and docking simulations were performed using Molecular Operating Environment software and the crystal structure of protein kinases CDK2, (1PYE) and AKT1 (4GV1), in addition to α-glucosidase (3TOP) and α-amylase (2QV4). RESULTS: Compounds 2, 3 and 8 were isolated for the first time from the plant and identified as: gmelinol (2), apigenin (3) and tyrosol (8). While ß-sitosterol-3-O- ß-D-glucopyranoside (4) vicenin-II (7), rhoifolin (9), isorhoifolin (11) were isolated for the first time from the genus, along with and the new iridoid 6-O-α-L-(2″-O-benzoyl-4″-O-trans-p-methoxycinnamoyl)rhamnopyranosyl-1α- ß-D-glucopyranoside catalpolgenin (6). In addition, to the previously reported compounds: mixture of ß -sitosterol and stigmasterol (1), and 6- O- α-L-(2″,3″,4″-tri-O -benzoyl)rhamnopyranosylcatalpol (5) and 6-O-α-L-(2″-O-trans-p-methoxycinnamoyl)rhamnopyranosylcatalpol (10). The cytotoxic activity against hepatocellular carcinoma (HepG-2) cell lines for compounds 2, 5, 7, 9 and 11 was conducted using cisplatin as a standard. Gmelinol (2) exhibited strong cytotoxic activity against HepG-2 cell lines with IC 50 value of 3.6 ± 0.1 µg/ml which is more potent than the standard cisplatin IC 50 = 8.7 ± 0.9 µg/ml. Molecular modeling of 2 against diverse targets of protein kinases suggested that CDK-2 and AKT-1 could be the dual probable kinase targets for its cytotoxic action. Compound 2 showed α-amylase inhibition activity with IC 50 value of 60.9 (µg/ml) while, compounds 5 showed strong α-glucosidase inhibition activity with IC 50 values of 41.7 (µg/ml) compared to acarbose with IC 50 value of 34.7, 30.6 (µg/ml). Molecular docking of compounds 2 and 5 on α-glucosidase (3TOP) and α-amylase (2QV4) enzymes revealed high binding affinity and active site interactions comparable to native ligand acarbose. CONCLUSION: The ethanolic extract of G. philippensis CHAM aerial parts is effective against HepG-2 cell lines, α-amylase and α-glucocidase activities. Biologically guided isolation indicated that compounds 2 and 5 are responsible for these activities. These results were supported by DMF calculations that detected the molecular areas responsible for protein interactions shown via docking studies.

Structural determination and anticholinesterase assay of C-glycosidic ellagitannins from Lawsonia inermis leaves: A study supported by DFT calculations and molecular docking.

An ellagitannin monomer, lythracin M (1), and a dimer, lythracin D (2), along with eight known monomers (3-10) were isolated from Lawsonia inermis (Lythraceae) leaves. Lythracin M (1) is a C-glycosidic ellagitannin with a flavogallonyl dilactone moiety that participates in the creation of a γ-lactone ring with the anomeric carbon of the glucose core. Lythracin D (2) was determined as an atropisomer of the reported lythcarin D. These newly discovered structures (1 and 2) were determined by intensive spectroscopic experiments and by comparing DFT-calculated 1H1H coupling, 1H NMR chemical shifts, and ECD data with experimental values. The anti-acetylcholinesterase assay of the compounds 1-10 revealed that the C-1 ellagitannin epimers [casuarinin (7; IC50 = 34 ± 2 nM) and stachyurin (8; IC50 = 56 ± 3 nM)], and the new dimer (2; IC50 = 61 ± 4 nM) possess enzyme inhibitory effects comparable to the reference drug (donepezil, IC50 = 44 ± 3 nM). Molecular docking of compounds 1-10 with AChE identified the free galloyl moiety as an important pharmacophore in the anticholinesterase activity of tannins.

Green synthesis of Ag2O nanoparticles using Punica granatum leaf extract for sulfamethoxazole antibiotic adsorption: characterization, experimental study, modeling, and DFT calculation.

Silver oxide (Ag2O) nanoparticles (NPs) were generated by synthesizing green leaf extract of Punica granatum, and afterwards they were used as adsorbent to remove the antibiotic additive sulfamethoxazole (SMX) from aqueous solutions. Prior of their use as adsorbent, the Ag2O NPs were characterized by various methods such as X-ray diffraction, Fourier transform infrared spectroscopy (FTIR), Brunauer-Emmett-Teller (BET), scanning electron microscopy/energy-dispersive X-ray (SEM-EDX), and transmission electron microscopy (TEM). The Ag2O NPs were found to be spherically shaped and stabilized by the constituents of the extract. Further, at SMX antibiotic concentration of 100 mg L-1, the Ag2O NPs achieved almost complete removal of 98.93% within 90 min, and by using 0.8 g L-1 of adsorbent dose at pH=4 and temperature T=308 K. In addition, the experimental data were well fitted with the theoretical Langmuir model indicating homogeneous adsorbed layer of the SMX antibiotic on the Ag2O NPs surface. The maximum uptake capacity was 277.85 mg g-1. A good agreement was also found between the kinetic adsorption data and the theoretical pseudo-second-order model. Regarding the thermodynamic adsorption aspects, the data revealed an endothermic nature and confirmed the feasibility and the spontaneity of the adsorption reaction. Furthermore, the regeneration study has shown that the Ag2O NPs could be efficiently reused for up to five cycles. The geometric structures have been optimized and quantum chemical parameters were calculated for the SMX unprotonated (SMX+/-) and protonated (SMX+) using density functional theory (DFT) calculation. The DFT results indicated that the unprotonated SMX+/- reacts more favorably on the Ag2O surface, as compared to the protonated SMX+. The SMX binding mechanism was predominantly controlled by the electrostatic attraction, hydrogen bond, hydrophobic, and π-π interactions. The overall data suggest that the Ag2O NPs have promising potential for antibiotic removal from wastewater.

Triple dehydrofluorination as a route to amidine-functionalized, aromatic phosphorus heterocycles.

An unexpected route to hitherto unknown amidine-functionalized phosphinines has been developed that is rapid and simple. Starting from primary amines and CF3-substituted λ3,σ2-phosphinines, a cascade of dehydrofluorination reactions leads selectively to ortho-amidinephosphinines. DFT calculations reveal that this unusual transformation can take place via a series of nucleophilic attacks at the electrophilic, low-coordinate phosphorus atom.

Revealing and Tuning the Photophysics of C=N Containing Photothermal Molecules: Excited State Dynamics Simulations.

Molecular photothermal conversion materials are recently attracting increasing attention for phototherapy applications. Herein we investigate the excitation and de-excitation processes of a photothermal molecule (C1TI) that is among the recently developed class of small-molecule-based photothermal imines with superb photothermal conversion efficiencies (PTCEs) up to 90% and a molecule (M2) that is constructed by replacing the amino group of C1TI with an H atom, via excited-state dynamics simulations based on the time-dependent density functional theory (TD-DFT). The simulations reveal fast (<150 fs of average time) nonradiative decays of the lowest excited singlet (S1) state to a conical intersection (CI) with the ground (S0) state in high yields (C1TI: 93.9% and M2: 87.1%). The fast decays, driven by C=N bond rotation to a perpendicular structural configuration, are found to be barrierless. The slight structural difference between C1TI and M2 leads to drastically different S0-S1 energy surfaces, especially M2 features a relatively much lower CI (0.8 eV in energy) and much more decay energy (1.0 eV) to approach the CI. This work provides insights into the de-excitation mechanisms and the performance tuning of C=N enabled photothermal materials.

Molecular-level insights into the mitigation of magnesium-natural organic matter induced ultrafiltration membrane fouling by high-dose calcium based on DFT calculation.

While magnesium cation (Mg2+) universally coexists with natural organic matter (NOM) in the water environment, influence of Mg2+ on NOM fouling in membrane filtration process is still unclear. This work was therefore performed to investigate effects of Mg2+ on NOM (sodium alginate (SA) as a model substance) fouling and role of Ca2+ in mitigating fouling from Mg2+ in the ultrafiltration (UF) water treatment process. Filtration tests showed two interesting fouling phenomena: (1) membrane fouling caused by combination of Mg2+ and SA maintained at a high value with the increased Mg2+ concentration; (2) the high fouling property of Mg2+ can be significantly improved by the prominent addition of calcium cation (Ca2+). It was found that changes of foulant morphology played essential roles through thermodynamic mechanisms represented by the Flory-Huggins lattice theory. Density functional theory (DFT) calculation showed that the combination of SA and Mg2+ tends to coordinate two terminal carboxyl groups in SA, beneficial to stretching alginate chains and forming a stable gel network at low doses. In addition, intramolecular coordination is difficult to occur between SA and Mg2+ due to the high hydration repulsion radius of Mg2+. Therefore, a dense and thick gel network remained even under high Mg2+concentration. Furthermore, due to the higher binding affinity of Ca2+ over Mg2+, high doses of Ca2+ trigger a transition of the stable SA-Mg2+ gel network to other configurations where flocculation and aggregation occur, thereby reducing the specific filtration resistance. The proposed thermodynamic mechanism satisfactorily explained the above interesting fouling behaviors, facilitating to development of new solutions to control membrane fouling.

Isolation, crystal structure, DFT calculation and molecular docking of uncinatine-A isolated from Delphinium uncinatum.

The main objective of our present research work was to explore molecular insight for potentially active new acetylcholinesterase inhibitor from the aerial parts of Delphinium uncinatum. New norditerpenoid alkaloids, uncinatine-A, was isolated from the basic alkaloidal fraction of D. uncinatum, based on bioactivity guided isolation. The structure of uncinatine-A was determined through latest spectroscopic techniques including single X-Ray diffraction technique. The structural data and electronic properties of uncinatine-A was also calculated by Density Functional Theory (DFT) using B3LYP/6-31þ G (p) basis set. The isolated natural product was evaluated for their acetyl cholinesterase inhibitory potential in dose dependent protocol (62.5-1000 µg/mL), followed by molecular docking studies. Significant competitive type inhibition activity (IC50 = 207.73 ± 0.3) was shown by isolated natural norditerpenoid against cholinesterase targets in comparison with standard drugs available in the market such as galanthamine. The molecular docking results showed that isolated natural product was well accommodated by AChE in the active site with docking scores -11.0326. This is the first report indicating uncinatine-A as a potent acetylcholinesterase inhibitor and can be used as a target drug in cerebral dementia and Alzheimer diseases.

Efficient model photosensitizers based on metallocenyl complexes with thiophene-N = N-pyrimidine as π-conjugated bridge and cyanoacrylate as an anchoring group: a density functional theory study.

Eight push-pull systems involving containing four transition metals (iron, ruthenium, cobalt, and nickel), metallocenes as donor groups, cyanoacrylate as electron attractor group, and thiophene-N = N- pyrimidine derivatives as π-conjugated bridges were designed and studied using DFT and TD-DFT methods involving B3LYP and CAM-B3LYP functionals combined with the cc-pVDZ/LANL2DZ basis sets. The main purpose of this work is to determine the effect of metallocene in improving the photosensitization property of such chromophores. This was done by calculating their light-harvesting efficiency LHE as well as other properties employed for DSSC application. The considered dyes were first studied in the gas phase, then in the presence of TiO2 nanoparticles representing the semi-conductor, and finally in the presence of a specific implicit solvent. The presence of iron as metal involved in the metallocene group supplemented by extending the π-conjugated bridge by a cyanovinyl spacer was demonstrated so as to give the most optimal response taking into account the lower cost and toxicity as well as the friendliness to the environment of iron as metal.

DFT Calculations of 31P NMR Chemical Shifts in Palladium Complexes.

In this study, comparative analysis of calculated (GIAO method, DFT level) and experimental 31P NMR shifts for a wide range of model palladium complexes showed that, on the whole, the theory reproduces the experimental data well. The exceptions are the complexes with the P=O phosphorus, for which there is a systematic underestimation of shielding, the value of which depends on the flexibility of the basis sets, especially at the geometry optimization stage. The use of triple-ζ quality basis sets and additional polarization functions at this stage reduces the underestimation of shielding for such phosphorus atoms. To summarize, in practice, for the rapid assessment of 31P NMR shifts, with the exception of the P=O type, a simple PBE0/{6-311G(2d,2p); Pd(SDD)}//PBE0/{6-31+G(d); Pd(SDD)} approximation is quite acceptable (RMSE = 8.9 ppm). Optimal, from the point of view of "price-quality" ratio, is the PBE0/{6-311G(2d,2p); Pd(SDD)}//PBE0/{6-311+G(2d); Pd(SDD)} (RMSE = 8.0 ppm) and the PBE0/{def2-TZVP; Pd(SDD)}//PBE0/{6-311+G(2d); Pd(SDD)} (RMSE = 6.9 ppm) approaches. In all cases, a linear scaling procedure is necessary to minimize systematic errors.

Jusanin, a New Flavonoid from Artemisia commutata with an In Silico Inhibitory Potential against the SARS-CoV-2 Main Protease.

A new flavonoid, Jusanin, (1) has been isolated from the aerial parts of Artemisia commutata. The chemical structure of Jusanin has been elucidated using 1D, 2D NMR, and HR-Ms spectroscopic methods to be 5,2',4'-trihydroxy-6,7,5'-trimethoxyflavone. Being new in nature, the inhibition potential of 1 has been estimated against SARS-CoV-2 using different in silico techniques. Firstly, molecular similarity and fingerprint studies have been conducted for Jusanin against co-crystallized ligands of eight different SARS-CoV-2 essential proteins. The studies indicated the similarity between 1 and X77, the co-crystallized ligand SARS-CoV-2 main protease (PDB ID: 6W63). To confirm the obtained results, a DFT study was carried out and indicated the similarity of (total energy, HOMO, LUMO, gap energy, and dipole moment) between 1 and X77. Accordingly, molecular docking studies of 1 against the target enzyme have been achieved and showed that 1 bonded correctly in the protein's active site with a binding energy of -19.54 Kcal/mol. Additionally, in silico ADMET in addition to the toxicity evaluation of Jusanin against seven models have been preceded and indicated the general safety and the likeness of Jusanin to be a drug. Finally, molecular dynamics simulation studies were applied to investigate the dynamic behavior of the Mpro-Jusanin complex and confirmed the correct binding at 100 ns. In addition to 1, three other metabolites have been isolated and identified to be сapillartemisin A (2), methyl-3-[S-hydroxyprenyl]-cumarate (3), and ß-sitosterol (4).

Human Serum Albumin Dimerization Enhances the S2 Emission of Bound Cyanine IR806.

Cyanine molecules are important phototheranostic compounds given their high fluorescence yield in the near-infrared region of the spectrum. We report on the frequency and time-resolved spectroscopy of the S2 state of IR806, which demonstrates enhanced emission upon binding to the hydrophobic pocket of human serum albumin (HSA). From excitation-emission matrix spectra and electronic structure calculations, we identify the emission as one associated with a state having the polymethine chain twisted out of plane by 103°. In addition, we find that this configuration is significantly stabilized as the concentration of HSA increases. Spectroscopic changes associated with the S1 and S2 states of IR806 as a function of HSA concentration, as well as anisotropy measurements, confirm the formation of HSA dimers at concentrations greater than 10 µM. These findings imply that the longer-lived S2 state configuration can lead to more efficient phototherapy agents, and cyanine S2 spectroscopy may be a useful tool to determine the oligomerization state of HSA.

Preparation of functionalized pectin through acylation with alkyl gallates: Experiments coupled with density functional theory.

The covalent grafting of alkyl gallates onto pectin using a lipase-catalyzed reaction in a tetrahydrofuran/aqueous medium process acylated pectin molecules with excellent antioxidant and antibacterial properties. The alkyl gallates including methyl, ethyl, and propyl gallates were enzymatically grafted onto pectin molecule, in order to study the effect of alkyl gallates on the functional modification of pectin. The grafting mechanism was analyzed by ultraviolet-visible spectrum (UV-Vis), Fourier transform infrared spectrum (FTIR), proton nuclear magnetic resonance (1HNMR), and density functional theory (DFT). Results suggested that lipase grafted 4-OH of alkyl gallate onto pectin by catalyzing esterification in organic/aqueous solution, and the grafting rate was affected by the length of alkyl chain of the gallates molecule. In vitro experiments, the acylated pectins exhibited stronger antioxidant activity in the DPPH test and ß-carotene bleaching test and were found to have obvious antimicrobial performance against Escherichia coli and Staphylococcus aureus.

The Ad-MD method to calculate NMR shift including effects due to conformational dynamics: The 31 P NMR shift in DNA.

A method for averaging of NMR parameters by molecular dynamics (MD) has been derived from the method of statistical averaging in MD snapshots, benchmarked and applied to structurally dynamic interpretation of the 31 P NMR shift (δ31P ) in DNA phosphates. The method employs adiabatic dependence of an NMR parameter on selected geometric parameter(s) that is weighted by MD-calculated probability distribution(s) for the geometric parameter(s) (Ad-MD method). The usage of Ad-MD for polymers is computationally convenient when one pre-calculated structural dependence of an NMR parameter is employed for all chemically equivalent units differing only in dynamic behavior. The Ad-MD method is benchmarked against the statistical averaging method for δ31P in the model phosphates featuring distinctively different structures and dynamic behavior. The applicability of Ad-MD is illustrated by calculating 31 P NMR spectra in the Dickerson-Drew DNA dodecamer. δ31P was calculated with the B3LYP/IGLO-III/PCM(water) and the probability distributions for the torsion angles adjacent to the phosphorus atoms in the DNA phosphates were calculated using the OL15 force field.

One order of magnitude increase of triplet state lifetime observed in deprotonated form selenium substituted uracil.

Selenium nucleic acids possess unique properties and have been demonstrated to have a wide range of applications such as in DNA X-ray crystallography and novel medical therapies. However, as a heavy atom, selenium substitution may easily alter the photophysical properties of a nucleic acid by red-shifting the absorption spectra and introducing effective intersystem crossing to triplet excited states. In present work, the excited state dynamics of a naturally occurring selenium substituted uracil (2-selenuracil, 2SeU) is studied by using femtosecond transient absorption spectroscopy as well as quantum chemistry calculations. Ultrafast intersystem crossing to the lowest triplet state (T1) and effective non-radiative decay of this state to the ground state (S0) are demonstrated in the neutral form 2SeU. However, the triplet lifetime of the deprotonated form 2SeU is found to be almost one order of magnitude longer than that in the neutral one. Quantum chemistry calculations indicate that the short triplet lifetime in 2SeU is due to excited state population decay through a crossing point between T1 and S0. In the deprotonated form, shortening the N1-C2 bond length makes the structural distortion more difficult and brings a larger energy barrier on the pathway to the T1/S0 crossing point, resulting in one order of magnitude increase of the triplet state lifetime. Our study reveals one key factor to regulate the triplet lifetime of 2SeU and sets the stage to further investigate the photophysical and photochemical properties of 2SeU-containing DNA/RNA duplexes.

Nutraceuticals in Bulk and Dosage Forms: Analysis by 35Cl and 14N Solid-State NMR and DFT Calculations.

This study uses 35Cl and 14N solid-state NMR (SSNMR) spectroscopy and dispersion-corrected plane-wave density functional theory (DFT) calculations for the structural characterization of chloride salts of nutraceuticals in their bulk and dosage forms. For eight nutraceuticals, we measure the 35Cl EFG tensor parameters of the chloride ions and use plane-wave DFT calculations to elucidate relationships between NMR parameters and molecular-level structure, which provide rapid NMR crystallographic assessments of structural features. We employ both 35Cl direct excitation and 1H→35Cl cross-polarization methods to characterize a dosage form containing α-d-glucosamine HCl, observe possible impurity and/or adulterant phases, and quantify the weight percent of the active ingredient. To complement this, we also investigate 14N SSNMR spectroscopy and DFT calculations to characterize nitrogen atoms in the nutraceuticals. This includes a discussion of targeted acquisition experimental protocols (i.e., acquiring a select region of the overall pattern that features key discontinuities) that allow ultrawideline spectra to be acquired rapidly, even for unreceptive samples (i.e., those with long values of T1(14N), short values of T2eff(14N), or very broad patterns). It is hoped that these experimental and computational protocols will be useful for the characterization of various solid forms of nutraceuticals (i.e., salts, polymorphs, hydrates, solvates, cocrystals, amorphous solid dispersions, etc.), help detect impurity and counterfeit solid phases in dosage forms, and serve as a foundation for future NMR crystallographic studies of nutraceutical solid forms, including studies using ab initio crystal structure prediction algorithms.

The Assignment of the Absolute Configuration of Non-Cyclic Sesquiterpenes by Vibrational and Electronic Circular Dichroism: The Example of Chiliadenus lopadusanus Metabolites.

9-Hydroxynerolidol, 9-oxonerolidol, and chiliadenol B are three farnesane-type sesquiterpenoids isolated from Chiliadenus lopadusanus that have shown an interesting activity against human pathogens as Gram+ and Gram- bacteria resistant to antibiotics. However, the absolute configuration (AC) of these interesting sesquiterpenes has not been assigned so far. Vibrational and electronic circular dichroism spectra have been recorded and correlations are pointed out for the three compounds. Density functional theory (DFT) calculations are used in conjunction with Mosher's method of investigation to assign AC. Statistical analysis is considered to quantitatively define the choice of AC from VCD spectra.

Construction of sulfur-containing compounds with anti-cancer stem cell activity using thioacrolein derived from garlic based on nature-inspired scaffolds.

Sulfur-containing compounds, such as cyclic compounds with a vinyl sulfane structure, exhibit a wide range of biological activities including anticancer activity. Therefore, the development of efficient strategies to synthesize such compounds is a remarkable achievement. We have developed a unique approach for the rapid and modular preparation of nature-inspired cyclic and acyclic sulfur-containing compounds using thioacrolein, a naturally occurring chemically unstable intermediate. We constructed thiopyranone derivatives through the regioselective sequential double Diels-Alder reaction of thioacrolein produced by allicin, a major component in garlic, and two molecules of silyl enol ether as the diene partner. The cytotoxicity toward cancer stem cells of the thiopyranones was equal to or higher than that of (Z)-ajoene (positive control) derived from garlic, and the thiopyranones had higher chemical stability than (Z)-ajoene.