2D Nuclear Overhauser Effect Spectroscopy Research Articles

Unveiling the conformational landscape of tizanidine and its effects on selective nucleation: Enabling controlled manipulation of polymorphs and solvates

The intricate relationship between conformational diversity and polymorphic nucleation is evident, while the underlying mechanisms remain unclear. In this work, tizanidine (TZND) was selected as the model compound to investigate its selective nucleation behavior and the association between conformations and polymorphs. Crystallization experiments were conducted using TZND in seven solvents, resulting in two polymorphs and four solvates, five of which are reported for the first time. Quantum chemical calculations were employed to explore the conformational landscape of TZND. Furthermore, 2D nuclear Overhauser effect spectroscopy and molecular dynamics were utilized to analyze the predominant conformation and its evolution in different solvents with varying concentrations. The results revealed that the dominant conformation of TZND could nucleate directly in methanol and acetone, while a conformational transition occurred during nucleation in acetonitrile and dichloromethane. Additionally, proton transfer in DMSO, chloroform, and DMF resulted in the emergence of new conformational forms. Moreover, crystallographic analysis, spectroscopic studies and quantum chemical calculations were adopted to investigate the molecular mechanisms governing selective nucleation and the formation of polymorphs or solvates. The results indicated that the free energy and solute–solvent interaction energy at specific sites influence the dominant conformation and its evolution in the solution. Finally, the nucleation mechanisms of different polymorphs and solvates were proposed and discussed, illustrating an efficient and environmentally friendly regulation method through solvent switching.

Probing noncovalent binding, spectroscopic characteristics and antiproliferative behavior of inclusion complex between quinoline and para-sulfonatothiacalix[4]arene

The inclusion complex between bowl-shaped para-sulfonatothiacalix[4]arene (TSCX4) macrocycle and quinoline has been studied with a unison of UV–visible, infra-red, flourescence emission and 1H nuclear magnetic resonance (NMR) and 2D nuclear overhauser effect spectroscopy (NOESY), high resolution mass spectrometry (HRMS) experiments. Both 1H NMR titration and HRMS experiments point to 1:1 stoichiometry for the water soluble Q⊂TSCX4 complex. The electronic structure of the inclusion complex obtained from density functional theory (DFT) showed a partial encapsulation of quinoline guest, which is held within the host cavity by C–H---π, π---π and hydrogen bonding interactions. The fluorescence emission spectra upon complexation display marginal blue shift of the 411 nm band in TSCX4. Moreover, the binding constant (7.1 × 103 M−1) determined from fluoresence emission experiments underline the effective host–guest binding in the complex, which was corroborated through frequency up-shift (‘blue shift’) of characteristic Ar-OH (3433 cm−1) and SO3- vibrations (1141 cm−1 and 1037 cm−1) in the measured infrared spectra of TSCX4. The antiproliferative activitities of the Q⊂TSCX4 complex against HeLA, MDA-MB-231and N2a cells are presented. The Q⊂TSCX4 complex has been shown to be efficient against N2a (neuroblastoma) cell line.

“Co-coordination force” assisted rigid-flexible coupling crystalline polymer for high-performance aqueous zinc-organic batteries

Organic electrode materials (OEMs) have attracted substantial attention for aqueous zinc-ion batteries (AZIBs) due to their advantages in relieving resource and environmental anxiety. However, the potential of OEMs is plagued by their low achievable capacity and high solubility. Here, we have proposed a new concept of “co-coordination force” and designed a rigid-flexible coupling crystalline polymer that can overcome the abovementioned limitations. The obtained crystalline polymer (BQSPNs) with multiredox centres makes the BQSPNs exist intermolecular hydrogen bonds (HB) among -C=O, -C=N, and -NH and consequently exhibits transverse two-dimensional arrays and longitudinal π-π stacking structure. Additionally, in-situ FTIR, Raman, variable temperature FTIR spectra, and 2D nuclear overhauser effect spectroscopy (NOESY) well capture the existence and evolution process of HB during the electrochemistry reaction process of BQSPNs, uncovering the effect of HB in stabilizing the structure and promoting the reaction kinetics. As a result, the BQSPNs with rationally designed “co-coordination force” deliver a high capacity of 459.6 mAh/g and a stable cycling lifetime for more than 100,000 cycles at 10 A/g in AZIBs. Our results disclose the HB effect and provide a brand-new strategy for high-performance OEMs design.

Cocrystallization of Gefitinib Potentiate Single-Dose Oral Administration for Lung Tumor Eradication via Unbalancing the DNA Damage/Repair.

Gefitinib (GEF) is a clinical medication for the treatment of lung cancer targeting the epidermal growth factor receptor (EGFR). However, its efficacy is remarkably limited by low solubility and dissolution rates. In this study, two cocrystals of GEF with co-formers were successfully synthesized using the recrystallization method characterized via Powder X-ray Diffraction, Fourier Transform Infrared Spectroscopy, and 2D Nuclear Overhauser Effect Spectroscopy. The solubility and dissolution rates of cocrystals were found to be two times higher than those of free GEF. In vitro cytotoxicity studies revealed that the cocrystals enhanced the inhibition of cell proliferation and apoptosis in A549 and H1299 cells compared to free GEF. In mouse models, GEF@TSBO demonstrated targeted, safe, and effective antitumor activity with only one-dose administration. Mechanistically, the GEF cocrystals were shown to increase the cellular levels of damaged DNA, while potentially downregulating PARP, thereby impairing the DNA repair machinery and leading to an imbalance between DNA damage and restoration. These findings suggest that the cocrystallization of GEF could serve as a promising adjunct to significantly enhance the physicochemical and biopharmaceutical performance for lung cancer treatment, providing a facial strategy to improve GEF anticancer efficiency with high bioavailability that can be orally administrated with only one dose.

Stereochemical assignment of clerodane-type diterpenes from the fruits of Casearia grewiifolia and their ability to inhibit PCSK9 expression

More than 20 natural products have been reported to modulate PCSK9-mediated cholesterol regulation, and small-molecule-derived proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors continue to be developed and identified. Here, twelve undescribed clerodane-type diterpenes (1–9 and 12–14) and two known compounds were isolated from the chloroform-soluble extract of the dried fruits of Casearia grewiifolia Vent. using a PCSK9 mRNA expression monitoring assay. Among the undescribed compounds, the stereochemistry of two diastereomeric grewiifolins A and B (1 and 2) were extensively elucidated using 2D Nuclear Overhauser Effect Spectroscopy (NOESY) experiments, excitation-sculptured indirect detection experiments (EXSIDE), interproton distance analyses, and computational calculations that included quantum chemical shift calculations combined with DP4+ analysis. All isolates were assessed for their inhibitory activity against PCSK9 and IDOL mRNA expression. Among the compounds tested, compound 3 inhibited PCSK9 and IDOL mRNA expression.

Ion clustering, aggregation and diffusion in amide based deep eutectic solvents: A microstructural investigation using various NMR spectroscopic techniques and molecular dynamics simulation

A thorough understanding of the structure and dynamics of deep eutectic solvents (DESs) is necessary to optimize the uses of this new class of solvents for many potential applications. Herein, we have studied ion clustering, aggregation and diffusion mechanism in DESs composed of acetamide and sodium/potassium thiocyanate using 1D NMR, pulsed field gradient stimulated echo (PFGSE) NMR and 2D nuclear Overhauser effect spectroscopy (2D NOESY) techniques, and molecular dynamics simulation. We have varied the fraction of salts to investigate the composition dependent microscopic structural insight. A great enhancement in diffusion coefficient (D) of acetamide with increasing the fraction of KSCN (fKSCN) has been observed in PFGSE measurements. The experimental diffusion activation energy (Ea) decreases significantly with increasing fKSCN, which is in excellent agreement with the Ea values obtained from simulated mean squared displacements (MSD). The calculated radial distribution functions (RDF) indicate that the Na+ ions strongly coordinate with acetamide molecules and form ion-clusters and aggregated structures in the medium. However, as Na+ ions are gradually replaced by K+ ions, ion-clustering and aggregation decrease due to relatively weak coordination ability of larger cation, which supports the enhancement of experimental D with increasing fKSCN. In the 2D NOESY study, the intensity of the cross peaks between methyl and amide protons of acetamide decreases relative to the diagonal peak intensity as the fKSCN increases in the medium. This study indicates that the extent of intermolecular NOE reduces as the structural flexibility increases due to less efficient ion-clustering with increasing K+ ion concentration, thus strongly corroborates the results from PFGSE experiment and simulation. Furthermore, 1D and 2D NMR data exhibit an intramolecular chemical exchange between two amide protons in acetamide, the extent of which increases with increasing temperature as well as fKSCN in the DES system. The present study provides a multifaceted picture of composition-dependent distinct microstructures in DES.

Smart Poly(lactide)-b-poly(triethylene glycol methyl ether methacrylate) (PLA-b-PTEGMA) Block Copolymers: One-Pot Synthesis, Temperature Behavior, and Controlled Release of Paclitaxel.

This paper introduces a new class of amphiphilic block copolymers created by combining two polymers: polylactic acid (PLA), a biocompatible and biodegradable hydrophobic polyester used for cargo encapsulation, and a hydrophilic polymer composed of oligo ethylene glycol chains (triethylene glycol methyl ether methacrylate, TEGMA), which provides stability and repellent properties with added thermo-responsiveness. The PLA-b-PTEGMA block copolymers were synthesized using ring-opening polymerization (ROP) and reversible addition-fragmentation chain transfer (RAFT) polymerization (ROP-RAFT), resulting in varying ratios between the hydrophobic and hydrophilic blocks. Standard techniques, such as size exclusion chromatography (SEC) and 1H NMR spectroscopy, were used to characterize the block copolymers, while 1H NMR spectroscopy, 2D nuclear Overhauser effect spectroscopy (NOESY), and dynamic light scattering (DLS) were used to analyze the effect of the hydrophobic PLA block on the LCST of the PTEGMA block in aqueous solutions. The results show that the LCST values for the block copolymers decreased with increasing PLA content in the copolymer. The selected block copolymer presented LCST transitions at physiologically relevant temperatures, making it suitable for manufacturing nanoparticles (NPs) and drug encapsulation-release of the chemotherapeutic paclitaxel (PTX) via temperature-triggered drug release mechanism. The drug release profile was found to be temperature-dependent, with PTX release being sustained at all tested conditions, but substantially accelerated at 37 and 40 °C compared to 25 °C. The NPs were stable under simulated physiological conditions. These findings demonstrate that the addition of hydrophobic monomers, such as PLA, can tune the LCST temperatures of thermo-responsive polymers, and that PLA-b-PTEGMA copolymers have great potential for use in drug and gene delivery systems via temperature-triggered drug release mechanisms in biomedicine applications.

Secondary Structure Characterization of Glucagon Products by Circular Dichroism and Nuclear Magnetic Resonance Spectroscopy.

Glucagon, a 29-amino acid polypeptide hormone, is an essential therapeutic agent used in the emergency treatment of hypoglycemia. However, glucagon is inherently unstable in aqueous solution. While glucagon equilibrates between unordered and the secondary α-helix state in solution, it can quickly transform into a different secondary β-sheet-rich amyloid-like fibril/oligomer structure under various conditions. Since changes in the secondary structure of glucagon can cause significant impacts, structure analysis is necessary and essential to assess the safety of the product. This study analyzed the secondary structure of glucagon products at the release and at the expiry using circular dichroism spectroscopy (CD) and 2D Nuclear Overhauser effect spectroscopy (2D NOESY). In order to also determine if structural differences exist between glucagon produced through different manufacturing processes, synthetic and recombinant glucagon products were used and compared. The CD results indicated that for all release and expired glucagon products, the structure compositions were 14 to 16% α-helix, 17 to 19% β-strand, 14 to 15% Turn, and 53 to 54% Unordered. This was consistent with the 2D NOESY analysis which showed that both products had an approximate α-helix composition of 14 to 17%. Overall, there were no significant differences in terms of the secondary structure between synthetic and recombinant glucagon products both at the release and at the expiry.

Use of Diethanolamine as a Viscous Solvent for Mixture Analysis by Multidimensional Heteronuclear ViscY NMR Experiments.

Diethanolamine/DMSO-d6 as a viscous binary solvent is first reported for the individualization of low-polarity mixture components by multidimensional heteronuclear ViscY NMR experiments under spin diffusion conditions. Solvent viscosity induces the slowing down of molecular tumbling, hence promoting magnetization transfer by dipolar longitudinal cross-relaxation. As a result, all 1H nuclei resonances within the same molecule may correlate in a 2D nuclear Overhauser effect spectroscopy (NOESY) spectrum, giving access to mixture analysis. We offer a new way to analyze mixtures by considering 3D heteronuclear heteronuclear single-quantum coherence-NOESY (HSQC-NOESY) experiments under viscous conditions. We state the individualization of four low-polarity chemical compounds dissolved in the diethanolamine/DMSO-d6 solvent blend using homonuclear selective 1D, 2D 1H-1H NOESY experiments and heteronuclear 1D, 2D 1H-19F heteronuclear Overhauser effect spectroscopy, 2D 1H-19F, 1H-31P HSQC-NOESY, and 3D 1H-19F-1H, 1H-31P-1H HSQC-NOESY experiments by taking profit from spin diffusion.

C–H⋯S Hydrogen Bond Assisted Supramolecular Encapsulation of Fullerenes with Nanobelts

C–H⋯S Hydrogen Bond Assisted Supramolecular Encapsulation of Fullerenes with Nanobelts

The Total Solubility of the Co-Solubilized PAHs with Similar Structures Indicated by NMR Chemical Shift.

The synergism/inhibition level, solubilization sites and the total solubility (St) of co-solubilization systems of phenanthrene, anthracene and pyrene in Tween 80 and sodium dodecyl sulfate (SDS) are studied by 1H-NMR, 2D nuclear overhauser effect spectroscopy (NOESY) and rotating frame overhauser effect spectroscopy (ROESY). In Tween 80, inhibition for phenanthrene, anthracene and pyrene is observed in most binary and ternary systems. However, in SDS, synergism is predominant. After analysis, we find that the different synergism or inhibition situation between Tween 80 and SDS is related to the different types of surfactants used and the resulting different co-solubilization mechanisms. In addition, we also find that three polycyclic aromatic hydrocarbons (PAHs) have similar solubilization sites in both Tween 80 and SDS, which are almost unchanged in co-solubilization systems. Due to the similar solubilization sites, the chemical shift changes of surfactant and PAH protons follow the same pattern in all solubilization systems, and the order of chemical shift changes is consistent with the order of changes in the St of PAHs. In this case, it is feasible to evaluate St of PAHs by chemical shift. In both Tween 80 and SDS solutions, the ternary solubilization system has relatively high St rankings. Therefore, in practical applications, a good overall solubilization effect can be expected.

Aggregation Behavior and Intermolecular Interaction of Cationic Trisiloxane Surfactants: Effects of Unsaturation.

Imidazolium/pyridinium-based trisiloxane surfactants containing a phenyl or vinyl group in the hydrophobic siloxane chain, bis(vinyldimethylsiloxy)methylsilylpropyl-pyridinium chloride (Vi-Si3pyrCl), bis(vinyldimethylsiloxy)methylsilylpropyl-imidazolium chloride (Vi-Si3minCl), and bis(phenyldimethylsiloxy)methylsilylpropylimidazolium chloride (Ph-Si3minCl), were synthesized and confirmed by nuclear magnetic resonance (NMR) (1H, 13C, and 29Si NMR), mass spectrometry, and Fourier transform infrared spectrometry. The effect of the phenyl/vinyl group on their micellization behavior was studied by surface tension, electric conductivity, dynamic light scattering, 2D nuclear Overhauser effect spectroscopy (NOESY) NMR, and transmission electron microscopy. Owing to the hydrophobicity of the siloxane groups and cationic head groups, the critical micelle concentration (cmc) values follow the order Ph-Si3minCl < Vi-Si3pyrCl < Vi-Si3minCl < Si3pyrCl. Ph-Si3minCl has a larger γcmc value, resulting from the introduction of the phenyldimethylsiloxy unit (π-π stacking interaction). The β values of Vi-Si3minCl and Ph-Si3minCl increase with the increase in temperature, which is attributed to the intermolecular interaction which hinders the association of Cl- with the imidazolium ring and confirmed by 2D NOESY NMR. In aqueous solutions, the investigated cationic trisiloxane surfactants can self-assemble into spherical aggregates.

Selective One-Dimensional 13C-13C Spin-Diffusion Solid-State Nuclear Magnetic Resonance Methods to Probe Spatial Arrangements in Biopolymers Including Plant Cell Walls, Peptides, and Spider Silk.

Two-dimensional (2D) and 3D through-space 13C-13C homonuclear spin-diffusion techniques are powerful solid-state nuclear magnetic resonance (NMR) tools for extracting structural information from 13C-enriched biomolecules, but necessarily long acquisition times restrict their applications. In this work, we explore the broad utility and underutilized power of a chemical shift-selective one-dimensional (1D) version of a 2D 13C-13C spin-diffusion solid-state NMR technique. The method, which is called 1D dipolar-assisted rotational resonance (DARR) difference, is applied to a variety of biomaterials including lignocellulosic plant cell walls, microcrystalline peptide fMLF, and black widow dragline spider silk. 1D 13C-13C spin-diffusion methods described here apply in select cases in which the 1D 13C solid-state NMR spectrum displays chemical shift-resolved moieties. This is analogous to the selective 1D nuclear Overhauser effect spectroscopy (NOESY) experiment utilized in liquid-state NMR as a faster (1D instead of 2D) and often less ambiguous (direct sampling of the time domain data, coupled with increased signal averaging) alternative to 2D NOESY. Selective 1D 13C-13C spin-diffusion methods are more time-efficient than their 2D counterparts such as proton-driven spin diffusion (PDSD) and dipolar-assisted rotational resonance. The additional time gained enables measurements of 13C-13C spin-diffusion buildup curves and extraction of spin-diffusion time constants TSD, yielding detailed structural information. Specifically, selective 1D DARR difference buildup curves applied to 13C-enriched hybrid poplar woody stems confirm strong spatial interaction between lignin and acetylated xylan polymers within poplar plant secondary cell walls, and an interpolymer distance of ∼0.45-0.5 nm was estimated. Additionally, Tyr/Gly long-range correlations were observed on isotopically enriched black widow spider dragline silks.

Relevance of π-stacking in tuning the neighboring structural pattern of soft nano-aggregates

Smart wormlike micellar blends can be readily formed from surfactant micelles in presence of counterion, salt or under varying conditions of pH, concentration, salinity driven by cation-π interaction whereas the role of π-π interaction in the same remains less explored. In this investigation the impact of π-π interaction on nanoaggregates of cationic amphiphile viz., cetylpyridinium bromide (CPB) in contrast with the cation-π interaction in cetyltrimethylammonium bromide (CTAB) in the presence of surface-active aromatic π conjugated hydroxy aromatic derivatives of naphthalene viz., 1 Naphthol, 2 Naphthol and 2,3 Dihydroxynaphthalene is reported. The presence of π-π interaction in CPB enables stronger synergism between the hydroxynaphthalenes compared to the non-aromatic analogue CTAB while face-to-face stacking interaction in CPB-hydroxynaphthalene systems lead to formation of worm like micelle (WLM) with relatively short entanglement lengths as compared to that in CTAB. The modification of surface parameters and molecular interactions of the systems are studied via tensiometry, 1H nuclear magnetic resonance (NMR), 2D-Nuclear Overhauser effect spectroscopy (NOESY) and small angle neutron study (SANS). The non-Newtonian behavior of the complex fluids comprising the cationic amphiphiles and hydroxyaromatic derivatives are studied using static and dynamic rheometry.

Micellization Behavior of Conventional Cationic Surfactants within Glycerol-Based Deep Eutectic Solvent.

The aggregation behavior of two cationic surfactants, i.e., cetyldimethylethanolammonium bromide (CDMEAB) and cetyltributylphosphonium bromide (CTBPB), within an aqueous deep eutectic solvent (DES) is studied. The synthesized DES is composed of 1:2 mole ratio of choline chloride and glycerol and is further characterized by Fourier transform infrared (FTIR) and 1H NMR spectroscopy techniques. The critical micellar concentration (CMC), micellar size, and intermolecular interaction in surfactants within Gly-based DES solutions are investigated by various techniques including surface tension, conductivity, fluorescence, dynamic light scattering (DLS), FTIR, 1H NMR, and two-dimensional (2D) nuclear Overhauser effect spectroscopy (NOESY). The various interfacial properties and thermodynamic parameters are determined in the presence of 5 wt % glyceline (Gly)-based DES in an aqueous solution. The CMC, aggregation number (Nagg), and Stern–Volmer constant (Ksv) have also been determined by a steady-state fluorescence method. DLS is used to obtain information regarding the size of the aggregates formed by the cationic surfactants in DES solutions. FTIR spectroscopy is used to study the surfactant–DES interactions that tune the micellar structure of the surfactants within the Gly-based DES solution. The functional groups involved in the interactions (H-bonding and electrostatic) are the head groups (HO–CH2–CH2–N+ ion for CDMEAB and quaternary phosphonium (P+) ion for CTBPB) of the surfactants with the −OH-containing Gly DES. The hydrophobic moieties are involved in the hydrophobic interactions. The 1H NMR data show that differences in chemical shifts can provide significant information about the interactions taking place within the system. 1H NMR and NOESY techniques are further employed to strengthen our claim on the feasible structural arrangements within the aqueous surfactant–DES self-assembled structures. It is observed that both the cationic surfactants, i.e., CDMEAB and CTBPB, form self-assembled nanostructures in the Gly-based DES solutions. The present results are expected to be useful for colloidal solutions of DES and their mixtures with water.

Study on the Surface Properties and Aggregation Behavior of Quaternary Ammonium Surfactants with Amide Bonds.

A number of techniques, including conductivity, surface tension, dynamic light scattering, transmission electron microscopy, and 1H nuclear magnetic resonance (1H NMR), Fourier transform infrared (FT-IR), and 1H–1H 2D nuclear Overhauser effect spectroscopy (1H–1H 2D NOESY), have been used to investigate the effect of amide bonds on the interfacial and assembly properties of a cationic surfactant, N-anilinoformylmethyl-N-cetyl-N,N-dimethyl ammonium chloride (AMC-C16), in aqueous solutions. The adsorption of AMC-C16 has been found to be much better than that of the conventional cationic surfactant, benzyl cetyldimethylammonium chloride (BAC-16) at the air/water interface and in solution. The surface tension measurements show the presence of two critical aggregation concentrations (CAC1 and CAC2) for AMC-C16. The presence of a strong intermolecular hydrogen bond of AMC-C16 was confirmed by 1H NMR and FT-TR. The molecular interactions of AMC-C16 were detected by 1H–1H 2D NOESY. The results show that the rigid group (phenyl) of AMC-C16 was partially overlapped with its alkyl chain in aqueous solution, and the possible aggregation behavior for AMC-C16 was proposed. The effects of an inorganic salt (NaCl) and an organic salt (C6H5COONa) to the aggregates of AMC-C16 have been discussed.

Molecular conformational evolution mechanism during nucleation of crystals in solution.

Nucleation of crystals from solution is fundamental to many natural and industrial processes. In this work, the molecular mechanism of conformational polymorphism nucleation and the links between the molecular conformation in solutions and in crystals were investigated in detail by using 5-nitro-furazone as the model compound. Different polymorphs were prepared, and the conformations in solutions obtained by dissolving different polymorphs were analysed and compared. The solutions of 5-nitro-furazone were proven to contain multiple conformers through quantum chemical computation, Raman spectra analysis, 2D nuclear Overhauser effect spectroscopy spectra analysis and molecular dynamics simulation. The conformational evolution and desolvation path was illustrated according to the 1H NMR spectra of solutions with different concentrations. Finally, based on all the above analysis, the molecular conformational evolution path during nucleation of 5-nitro-furazone was illustrated. The results presented in this work shed a new light on the molecular mechanism of conformational polymorphism nucleation in solution.

Recognition Selectivities of Lasso-Type Pseudo[1]rotaxane Based on a Mono-Ester-Functionalized Pillar[5]arene.

Two types of mono-ester-functionalized pillar[5]arenes, P1 and P2, bearing different side-chain groups, were synthesized. Their host–guest complexation and self-inclusion properties were studied by 1H NMR and 2D nuclear overhauser effect spectroscopy (NOESY) NMR measurements. The results showed that the substituents on their phenolic units have a great influence on the self-assembly of both pillar[5]arenes, although they both could form stable pseudo[1]rotaxanes at room temperature. When eight bulky 4-brombutyloxy groups were capped on the cavity, instead of methoxy groups, pseudo[1]rotaxane P1 became less stable and its locked ester group in the inner space of cavity was not as deep as P2, leading to distinctly different host–guest properties between P1 and P2 with 1,6-dibromohexane. Moreover, pillar[5]arene P1 displayed effective molecular recognition toward 1,6-dichlorohexane and 1,2-bromoethane among the guest dihalides. In addition, the self-complex models and stabilities between P1 and P2 were also studied by computational modeling and experimental calculations.

Characterization of Inclusion Complex of Coenzyme Q10 with the New Carrier CD-MOF-1 Prepared by Solvent Evaporation.

The aim of the current study was to evaluate the physicochemical properties of a solid dispersion of coenzyme Q10 (CoQ10)/cyclodextrin metal organic frameworks-1 (CD-MOF-1). As a result of the powder X-ray diffraction (PXRD), it was confirmed that the CD-MOF-1 was changed from the α form to the β form by evaporation (EVP). A diffraction peak due to melting of CoQ10 disappeared the EVP (CoQ10/CD-MOF-1 = 1/2). The structure of this complex is presumed to be similar to the β form of CD-MOF-1. As a result of the differential scanning calorimetry (DSC), the endothermic peak due to the melting of CoQ10 disappeared the EVP (CoQ10/CD-MOF-1 = 1/2). As a result of the near-infrared (NIR) absorption spectroscopy, findings suggested the hydrogen bond in formation between the CH group in the isoprene side chains of CoQ10 and the OH group of CD-MOF-1. Therefore, the formation of crystal solid dispersion in CoQ10/CD-MOF-1 was suggested. As a result of the dissolution test in distilled water, the EVP (CoQ10/CD-MOF-1 = 1/2) had better dissolution in comparison to CoQ10 alone. Furthermore, also in fasted state simulated intestinal fluid (FaSSIF) in vivo, the EVP (CoQ10/CD-MOF-1 = 1/2) had better dissolution in the human body than CoQ10 alone. From the results of 2D-nuclear overhauser effect spectroscopy (NOESY) NMR spectroscopy, CD-MOF-1 could not include the benzoquinone ring of CoQ10. It was confirmed that the isoprene side chain was included. Therefore, it was suggested that CD-MOF-1 useful as a novel drug carrier for CoQ10.

5-Hydroxy-3-(4-hydroxyphenyl)-8,8-dimethyl-6-(3-methylbut-2-enyl)pyrano[2,3-h]chromen-4-one

Natural and semi-synthetic compounds are being studied as novel phosphodiesterase 5 (PDE5) inhibitors for the treatment of erectile dysfunction, pulmonary hypertension, and lower urinary symptoms. Maclura pomifera is a source of flavonoids, one of the main classes of molecules investigated for these purposes. The extraction of the natural isoflavone osajin and its modification to obtain a semi-synthetic derivative are described in this short note. 1H and 13C-nuclear magnetic resonance spectroscopy (NMR), mass spectrometry, high-performance liquid chromatography (HPLC) and spectroscopic characterization of the title compound are also hereby provided. Two-dimensional (2D) nuclear Overhauser effect spectroscopy (NOESY) NMR, supported by in silico conformational studies, was used to achieve a complete assignment of the proton signals, assessing the correct chemical structure of the compound. Heteronuclear single quantum coherence spectroscopy (HSQC) and heteronuclear multiple bond correlation (HMBC) NMR experiments were performed to assign 13C chemical shifts. Calculated chemical properties and preliminary in silico docking suggest that this molecule might be a promising candidate as PDE5 inhibitor.