Synthesis and NMR spectral studies of N-chloroacetyl-2,6-diarylpiperidin-4-ones

A series of 2,6-diarylpiperidin-4-ones having electron withdrawing chloroacetyl group at the heterocyclic nitrogen were synthesized. Unambiguous characterizations of the synthesized compounds were achieved by one-dimensional ((1)H NMR and (13)C NMR) and two-dimensional (HOMOCOSY, NOESY and HSQC spectra for compounds 8 and 9 and HOMOCOSY spectrum only for 10) NMR spectroscopic data. The conformational preferences of N-chloroacetyl-2,6-diarylpiperidin-4-ones with and without alkyl substituent at C-3 and C-5 (8-14) have also been discussed using the spectral studies. The spectral data and extracted coupling constant values suggest that the compounds 8, 12 and 14 adopt flattened boat conformation whereas the remaining compounds exist in twist-boat conformations in solution with coplanar orientation of the chloroacetyl moiety present at the heterocyclic nitrogen. The substituent parameters for the chloroacetyl moiety on the heterocyclic ring carbons have also been derived and discussed elaborately on the basis of their steric, electronic and gamma-eclipsing interaction. This substituent at the nitrogen causes a substantial change on the chemical shifts of ring carbons and the associated protons.     

Substituent and solvent effects on electronic spectra of some substituted phenoxyacetic acids

The effects of substituents and solvents have been studied through the absorption spectra of nearly 19 para- and ortho-substituted phenoxyacetic acids in the range of 200-400 nm. The effects of substituent on the absorption spectra of compounds under present investigation are interpreted by correlation of absorption frequencies with simple and extended Hammett equations. Effect of solvent polarity and hydrogen bonding on the absorption spectra are interpreted by means of Kamlet equation and the results are discussed.     

β‐Iminoenamine‐BF2 Complexes: Aggregation‐Induced Emission and Pronounced Effects of Aliphatic Rings on Radiationless Deactivation

The synthesis, photophysical, and electrochemical attributes of a novel class of boron difluorides containing an aromatic‐fused alicyclic/hetero‐alicyclic ring built on a β‐iminoenamine chromophoric backbone are reported. The compounds displayed large Stokes shifts (86–121 nm), and were emissive in the solid state. The quantum yields obtained in solution at room temperature were unusually lower by an order of magnitude compared to those in the solid state. Some of the tested compounds displayed aggregation‐induced emission (AIE). Single crystal XRD analyses revealed a lack of interplanar π–π interactions, which are presumed to be absent owing to non‐planarity of the alicyclic component in the molecule. For most of the studied compounds, time‐dependent DFT (TD‐DFT) calculations invariably reveal intramolecular charge transfer (π–π*) characteristics with the frontier orbitals concentrated on the boron–nitrogen heterocycle. The participation of boron and fluorine atoms was found to be negligible.     

Designing Gelatin Methacryloyl (GelMA)‐Based Bioinks for Visible Light Stereolithographic 3D Biofabrication

Bioinks play a key role in determining the capability of the biofabricatoin processes and the resolution of the printed constructs. Excellent biocompatibility, tunable physical properties, and ease of chemical or biological modifications of gelatin methacryloyl (GelMA) have made it an attractive choice as bioinks for biomanufacturing of various tissues or organs. However, the current preparation methods for GelMA‐based bioinks lack the ability to tailor their physical properties for desired bioprinting methods. Inherently, GelMA prepolymer solution exhibits a fast sol–gel transition at room temperature, which is a hurdle for its use in stereolithography (SLA) bioprinting. Here, synthesis parameters are optimized such as solvents, pH, and reaction time to develop GelMA bioinks which have a slow sol–gel transition at room temperature and visible light crosslinkable functions. A total of eight GelMA combinations are identified as suitable for digital light processing (DLP)‐based SLA (DLP‐SLA) bioprinting through systematic characterizations of their physical and rheological properties. Out of various types of GelMA, those synthesized in reverse osmosis (RO) purified water (referred to as RO‐GelMA) are regarded as most suitable to achieve high DLP‐SLA printing resolution. RO‐GelMA‐based bioinks are also found to be biocompatible showing high survival rates of encapsulated cells in the photocrosslinked gels. Additionally, the astrocytes and fibroblasts are observed to grow and integrate well within the bioprinted constructs. The bioink's superior physical and photocrosslinking properties offer pathways of tuning the scaffold microenvironment and highlight the applicability of developed GelMA bioinks in various tissue engineering and regenerative medicine applications.     

1H and 13C NMR spectral assignments of some novel 2,4,6,8-tetraaryl-3,7-diazabicyclo[3.3.1]nonan-9-one derivatives

The (1)H and (13)C NMR spectra of 2,4,6,8-tetraaryl-3,7-diazabicyclo[3.3.1]nonan-9-ones (1-2), oximes (3-8) and O-benzyl oximes (9-12) were recorded. The chemical shifts were unambiguously assigned using 1D and 2D NMR spectral data. The results clearly indicate that the compounds exist in chair-boat conformation with equatorial and axial orientation of the aryl groups in the chair and boat forms, respectively. Since the molecules are flexible and dynamic in solution, the chair and boat forms are mutually interconvertible. In 3-12, because of the effect of oximation/oximination, all the protons in the heterobicyclic systems gave distinct signals except the benzylic protons of the boat form. In all synthesized compounds, the aryl group protons at C-6,8 are shielded by the aryl groups at C-2,4 and therefore appear in the lower frequency region than the aryl groups at C-2,4.     

Kinetics of oxidation of some ortho,meta, and para substituted S-phenylmercaptoacetic Acids by N-Chloro-3-Methyl-2,6-Diphenyl piperidin-4-one in buffered ethanol-water

The kinetics of oxidation of a number of ortho, meta, and para substituted S-phenylmercaptoacetic acids by N-Chloro-3-Metyl-2,6-Diphenylpiperidin-4-one (NCP) has been studied in buffered ethanol-water (75:25 v/v) of pH 5.46. The reaction is of first order each in [oxidant] and [substrate]. The rate constant decreases with increase in pH from 5.22 to 5.70. The reaction is accelerated by electron releasing and retarded by electron withdrawing substitutents. The ρ value obtained for this reaction is ?1.88 at 10°C with a good correlation coefficient of 0.99 showing an electron deficient transition state. The effect of ortho substitutents also is discussed in detail.     

Aphrodisiac Performance of Bioactive Compounds from Mimosa pudica Linn.: In Silico Molecular Docking and Dynamics Simulation Approach

Plants and their derived molecules have been traditionally used to manage numerous pathological complications, including male erectile dysfunction (ED). Mimosa pudica Linn. commonly referred to as the touch-me-not plant, and its extract are important sources of new lead molecules in drug discovery research. The main goal of this study was to predict highly effective molecules from M. pudica Linn. for reaching and maintaining penile erection before and during sexual intercourse through in silico molecular docking and dynamics simulation tools. A total of 28 bioactive molecules were identified from this target plant through public repositories, and their chemical structures were drawn using Chemsketch software. Graph theoretical network principles were applied to identify the ideal target (phosphodiesterase type 5) and rebuild the network to visualize the responsible signaling genes, proteins, and enzymes. The 28 identified bioactive molecules were docked against the phosphodiesterase type 5 (PDE5) enzyme and compared with the standard PDE5 inhibitor (sildenafil). Pharmacokinetics (ADME), toxicity, and several physicochemical properties of bioactive molecules were assessed to confirm their drug-likeness property. Molecular dynamics (MD) simulation modeling was performed to investigate the stability of PDE5–ligand complexes. Four bioactive molecules (Bufadienolide (−12.30 kcal mol⁻¹), Stigmasterol (−11.40 kcal mol⁻¹), Isovitexin (−11.20 kcal mol⁻¹), and Apigetrin (−11.20 kcal mol⁻¹)) showed the top binding affinities with the PDE5 enzyme, much more powerful than the standard PDE5 inhibitor (−9.80 kcal mol⁻¹). The four top binding bioactive molecules were further validated for a stable binding affinity with the PDE5 enzyme and conformation during the MD simulation period as compared to the apoprotein and standard PDE5 inhibitor complexes. Further, the four top binding bioactive molecules demonstrated significant drug-likeness characteristics with lower toxicity profiles. According to the findings, the four top binding molecules may be used as potent and safe PDE5 inhibitors and could potentially be used in the treatment of ED.