Malabaricone C, a constituent of spice Myristica malabarica, exhibits anti-inflammatory effects via modulation of cellular redox.

The present study primarily focuses on the efficacy of Malabaricone C (Mal C) as an anti-inflammatory agent. Mal C inhibited mitogen-induced T-cell proliferation and cytokine secretion. Mal C significantly reduced cellular thiols in lymphocytes. N-acetyl cysteine (NAC) restored cellular thiol levels and abrogated Mal C-mediated inhibition of T-cell proliferation and cytokine secretion. Physical interaction between Mal C and NAC was evinced from HPLC and spectral analysis. Mal C treatment significantly inhibited concanavalin A-induced phosphorylation of ERK/JNK and DNA binding of NF-κB. Administration of Mal C to mice suppressed T-cell proliferation and effector functions ex vivo. Mal C treatment did not alter the homeostatic proliferation of T-cells in vivo but completely abrogated acute graft-versus-host disease (GvHD)-associated morbidity and mortality. Our studies indicate probable use of Mal C for prophylaxis and treatment of immunological disorders caused due to hyper-activation of T-cells.

Synthesis of Dihydrobenzofuro[3,2-b]chromenes as Potential 3CLpro Inhibitors of SARS-CoV-2: A Molecular Docking and Molecular Dynamics Study.

The recent emergence of pandemic of coronavirus (COVID-19) caused by SARS-CoV-2 has raised significant global health concerns. More importantly, there is no specific therapeutics currently available to combat against this deadly infection. The enzyme 3-chymotrypsin-like cysteine protease (3CLpro) is known to be essential for viral life cycle as it controls the coronavirus replication. 3CLpro could be a potential drug target as established before in the case of severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). In the current study, we wanted to explore the potential of fused flavonoids as 3CLpro inhibitors. Fused flavonoids (5a,10a-dihydro-11H-benzofuro[3,2-b]chromene) are unexplored for their potential bioactivities due to their low natural occurrences. Their synthetic congeners are also rare due to unavailability of general synthetic methodology. Here we designed a simple strategy to synthesize 5a,10a-dihydro-11H-benzofuro[3,2-b]chromene skeleton and it's four novel derivatives. Our structural bioinformatics study clearly shows excellent potential of the synthesized compounds in comparison to experimentally validated inhibitor N3. Moreover, in-silico ADMET study displays excellent druggability and extremely low level of toxicity of the synthesized molecules. Further, for better understanding, the molecular dynamic approach was implemented to study the change in dynamicity after the compounds bind to the protein. A detailed investigation through clustering analysis and distance calculation gave us sound comprehensive data about their molecular interaction. In summary, we anticipate that the currently synthesized molecules could not only be a potential set of inhibitors against 3CLpro but also the insights acquired from the current study would be instrumental in further developing novel natural flavonoid based anti-COVID therapeutic spectrums.

Investigation of Morphology-Controlled Ultrafast Relaxation Processes of Aggregated Porphyrin.

Here, we have synthesized rod and flake shaped morphology of porphyrin aggregates from 5, 10, 15, 20-tetra (4-n-octyloxyphenyl) porphyrin (4-opTPP) molecule which are evident from scanning electron microscopy (SEM). The formation of J-type aggregation is evident from steady state and time-resolved fluorescence spectroscopic studies. Ultrafast transient absorption spectroscopic studies reveal that the excited state lifetime is controlled by the morphology and the time constant for S1→S0 relaxation changes from 3.05 ps to 744 ps with changing the shape from rod to flake, respectively. In spite of similar exciton coupling energy in both the aggregates, the flake shaped aggregates undergo a faster exciton relaxation process and the non-radiative relaxation channels are found to depend on the shape of aggregates. The fundamental understanding of morphology controlled ultrafast relaxation processes of aggregated porphyrin is important for designing efficient light harvesting devices.

Catalytic Oxidation of 3-Arylbenzofuran-2(3 H)-ones with PCC-H5IO6: Syntheses of 3-Aryl-3-hydroxy/3-amido-3-arylbenzofuran-2(3 H)-ones.

A pyridinium chlorochromate (PCC)-mediated facile oxidative dimerization of 3-arylbenzofuran-2-ones at ambient temperature was developed which undergo oxidative cleavage to 3-aryl-3-hydroxy-benzofuran-2-ones with PCC at elevated temperatures. Finally, direct oxidation of 3-arylbenzofuran-2-ones to 3-aryl-3-hydroxy-benzofuran-2-ones was realized using a combination of PCC (10 mol %) and 2.0 equiv of H5IO6. The synthesized 3-aryl-3-hydroxy-benzofuranones were further converted to corresponding 3-amido-3-aryl-benzofuranones in high yields by Ritter reaction. Thus, the present protocol provides a nonconventional approach to C-3 hydroxylation of 3-arylbenzofuranones via their dimer using a catalytic amount of inexpensive chromium(VI) oxidant.

Total Syntheses of Malabaricones B and C via a Cross-Metathesis Strategy.

The malabaricones A-D belong to the class of diarylnonanoids isolated from the Myristicaceae family of plants. Although malabaricone C displayed various interesting biological activities, its isolation remains tedious due to its close chemical similarity to malabaricones A, B, and D. Therefore, development of an efficient synthesis route has become essential to cater to the need of large amounts of malabaricone C for its pharmacological profiling. So far there is only one report of the synthesis of malabaricone C through a lengthy sequence of reactions. We have developed an efficient and short route for the syntheses of malabaricones B and C, which will also provide a convenient access to all other members of the malabaricone family. Synthesis of an important building block, ω-aryl heptyl bromide, employed in the synthesis was realized by adopting a cross-metathesis reaction as the key step.

Recognition of steric factor in external association of xanthenocrown-5 and bis-napthalenocrown-6 with bis(benzimidazolium)propane borontetrafluoride.

This is the first report of charge transfer band for crown-axel H-bonding interaction in acetonitrile medium. Monte Carlo simulation established external association of small cavity crown with BBIM-propane dication axels. Resonance energy, binding constant and ratiometric detection of association of xanthenocrown-5 (1) and bis-napthalenocrown-6 (2) with bis-(benzimidazolium)propane borontetrafluoride (3a-3d) in acetonitrile determined the effect of steric factor towards association.

Photon Harvesting in Sunscreen-Based Functional Nanoparticles.

The ultraviolet light component in the solar spectrum is known to cause several harmful effects, such as allergy, skin ageing, and skin cancer. Thus, current research attention has been paid to the design and fundamental understanding of sunscreen-based materials. One of the most abundantly used sunscreen molecules is Avobenzone (AB), which exhibits two tautomers. Here, we highlight the preparation of spherically shaped nanoparticles from the sunscreen molecule AB as well as from sunscreen-molecule-encapsulated polymer nanoparticles in aqueous media and study their fundamental photophysical properties by steady-state and time-resolved spectroscopy. Steady-state studies confirm that the AB molecule is in the keto and enol forms in tetrahydrofuran, whereas the enol form is stable in the case of both AB nanoparticles and AB-encapsulated poly(methyl methacrylate) (PMMA) nanoparticles. Thus, the keto-enol transformation of AB molecules is restricted to a nanoenvironment. An enhancement of photostability in both the nanoparticle and PMMA-encapsulated forms under UV light irradiation is observed. The efficient excited energy transfer (60 %) from AB to porphyrin molecules opens up further prospects in potential applications as light-harvesting systems.

PyC60-naphthacrown system: a new supramolecular recognition element.

Fulleropyrrolidine (PyC60) and a binaphthyl bridged crown ether macrocyclic receptor (1) undergoes spontaneous self-assembly phenomenon in solution to generate a new supramolecular recognition element having binding constant value of ∼5.83×10(4)dm(3)mol(-1). Lifetime measurement reveals a static quenching mechanism behind the deactivation of photoexcited state of 1 in presence of PyC60. The results obtained from this work would definitely reinforce bridged cyclic crown ether as one of the most suitable fragments for the molecular recognition of various macrocyclic receptor(s) in near future.

Silicon-pyrene/perylene hybrids as molecular rectifiers.

We have synthesized two alkenyl (C-6 and C-11 chains) pyrenes and one alkenyl (C-11 chain) perylene as the σ-π systems, which were electro-grafted on H-terminated Si surfaces to form the respective monolayers. The I-V characteristics of the monolayers revealed pronounced rectification in forward bias with a maximum rectification ratio (RR) of 2.5 × 10(5) at 2.5 V for the C-6-pyrene 4b, 1000 at 1.5 V for the C-11-pyrene 4a and 3000-5000 at 1.75 V for the C-11-perylene 3. The higher RR of the devices containing 4b compared to those of 4a and 3 is possibly due to better alignment and packing of the 4b-monolayers on the Si substrate. The rectification was explained using the ab initio molecular-orbital calculations.

Surfactant-assisted porphyrin based hierarchical nano/micro assemblies and their efficient photocatalytic behavior.

In this report, we have demonstrated the synthesis of surfactant-assisted different morphologies of meso-tetra(4-carboxyphenyl)porphyrin assemblies (spherical to flower shaped). These nano/micro assemblies are well characterized by scanning electron microscopy and X-ray diffraction. The formation of assemblies is driven by noncovalent interactions such as hydrophobic-hydrophobic and aromatic π-π stacking between the molecules. The steady state and time-resolved spectroscopic investigation reveal that different assemblies are formed by virtue of special supramolecular organizations. The photocatalytic activities of different assemblies have been demonstrated with an organic pollutant Rhodamine B dye under the visible light irradiation. Such porphyrin based assemblies could pave the way for designing new optical based materials for the applications in photocatalytic, photovoltaic, and light harvesting system.

New strigolactone mimics: structure-activity relationship and mode of action as germinating stimulants for parasitic weeds.

Strigolactones (SLs) are new plant hormones with varies important bio-functions. This Letter deals with germination of seeds of parasitic weeds. Natural SLs have a too complex structure for synthesis. Therefore, there is an active search for SL analogues and mimics with a simpler structure with retention of activity. SL analogues all contain the D-ring connected with an enone moiety through an enol ether unit. A new mechanism for the hydrolysis SL analogues involving bidentate bound water and an α,ß-hydrolase with a Ser-His-Asp catalytic triad has been proposed. Newly discovered SL mimics only have the D-ring with an appropriate leaving group at C-5. A mode of action for SL mimics was proposed for which now supporting evidence is provided. As predicted an extra methyl group at C-4 of the D-ring blocks the germination of seeds of parasitic weeds.

Supramolecular interaction of coumarin 1 dye with cucurbit[7]uril as host: combined experimental and theoretical study.

Molecules of the coumarin family have fluorescence characteristics that are highly sensitive to their environment, and thus, they have been used as fluorescent sensors in chemical and biological systems. However, the very poor fluorescence yield of most coumarin dyes in aqueous media limits their applications. We have adopted a supramolecular strategy to improve the fluorescence intensity of coumarin dye through its interaction with the relatively new host cucurbit[7]uril (CB[7]). The virtually nonfluorescent coumarin 1 (Φ(f) = 0.04) was converted into a highly fluorescent (Φ(f) = 0.52) entity in water upon addition of the nonfluorescent host CB[7]. Various spectroscopy techniques, namely, UV-vis absorption and steady-state and time-resolved fluorescence spectroscopies, established the formation of a strong 1:1 dye-CB[7] inclusion complex with a high binding constant of (1.2 ± 0.1) × 10(5) M(-1) for the dye. The stable inclusion complex of the neutral molecule was supported by density-functional-theory- (DFT-) based quantum chemical calculations. Energy decomposition analysis of various interaction factors in the host-guest complex revealed that key components providing stability to the complex were electrostatic, polarization, and charge-transfer energies. These new results on the formation of a strong inclusion complex of the versatile fluorophore coumarin 1 with the nontoxic host CB[7] could lead to the design of efficient molecular-scale biological probes, sensors, and photostable aqueous UV dye lasers.

Absorption spectrophotometric, NMR and theoretical investigations on ground state non-covalent interaction of C60 and C70 with a designed trihomocalix[6]arene in solution.

The present paper reports the spectroscopic investigations on non-covalent interaction of fullerenes C(60) and C(70) with a designed trihomocalix[6]arene (2) in toluene. UV-vis studies reveal appreciable ground state interaction between fullerenes and 2. Jobs method of continuous variation establishes 1:1 stoichiometry for fullerene-2 complexes. Binding constant (K) data reveals that 2 binds C(70) more strongly compared to C(60), i.e. K(C60-2)-47,540 dm(3)mol(-1) and K(C70-2)-86,360 dm(3)mol(-1). Proton NMR studies provide very good support in favor of strong binding between C(70) and 2. Estimation of solvent reorganization energy (R(S)) evokes that C(70)-2 complex is stabilized more compared to C(60)-2 complex as R(S(C60-2))- -1.162 eV and R(S(C70-2))- -1.244eV. Semiempirical calculations at third parametric level of theory in vacuo evoke the single projection structures of the fullerene-2 complexes and interpret the stability difference between C(60) and C(70) complexes of 2 in terms of enthalpies of formation values.

UV-Vis, fluorescence and NMR spectroscopic investigations on inclusion properties of a designed tetrahomocalix[8]arene with fullerenes C60 and C70 in solution.

The present article reports the spectroscopic investigations on non-covalent interaction of fullerenes C(60) and C(70) with a macrocyclic receptor molecule, namely, 1,3,5,7-tetrahomo-p-tert-butylcalix[8]arene (1) in toluene. Jobs method of continuous variation reveals 1:1 stoichiometry for the fullerene complexes of 1. The most fascinating feature of the present study is that 1 binds selectively C(60) compared to C(70) as obtained from binding constant (K) data of C(60)-1 (K(C60-1)) and C(70)-1 (K(C70-1)) complexes which are enumerated to be 265,000 dm(3) mol(-1) and 63,43 dm(3) mol(-1), respectively, and selectivity in binding (K(C60-1)/K(C70-1)) is estimated to be 4.18 as obtained from UV-Vis study. Steady state fluorescence studies reveal quenching of fluorescence of 1 in presence of fullerenes and the K value of the C(60)-1 and C(70)-1 complexes are estimated to be 80,760 and 68,780 dm(3) mol(-1), respectively, with selectivity in binding (K(C60-1)/K(C70-1)) ~1.18. (1)H NMR analysis provides very good support in favor of strong binding between C(60) and 1. The high value of K value for C(60)-1 complex indicates that 1 forms an inclusion complex with C(60).

Spectroscopic and theoretical insights into the origin of fullerene-calix[4]pyrrole interaction.

The present paper reports, for the first time, supramolecular interaction of meso-octamethyl calix[4]pyrrole (1) with fullerenes C(60) and C(70) in solutions having varying polarity (e.g., toluene, 1,2-dichlorobenzene and benzonitrile and chloroform). The interaction is facilitated through charge transfer (CT) transition as evidenced from well-defined CT absorption bands in the visible region of absorption spectroscopy. Utilizing the CT transition energy for the complexes of 1 with various electron acceptors, we have determined the ionization potential of 1. Estimation of degrees of CT, oscillator, and transition dipole strengths suggest that the complexes are almost of neutral character in ground state. Higher magnitude of electronic coupling element value for the C(70)-1 complex compared to C(60)-1 indicates strong binding between C(70) and 1. Binding constants (K) of the fullerene-1 complexes have been determined from UV-vis investigations, which indicate high selectivity of 1 toward C(70). Extraordinary large K value of the C(70)-1 complex in chloroform medium (K approximately 1.43 x 10(6) dm(3) x mol(-1)) establishes that a polar environment facilitates such interaction. Both proton NMR and liquid IR studies provide very good support in favor of strong binding between C(70) and 1. (13)C NMR study proves that C(70) binds 1 with its equatorial belt, which substantiates the role of pi-pi interaction behind such strong interaction (i.e., high K value). Semiempirical theoretical calculations at the third parametric level (PM3) explore the stability difference between C(60)- and C(70)-1 complexes. PM3 calculations also reveal that approach of C(70) toward 1 is directed in side-on manner rather than in a conventional end-on alignment.

Environmental effects on luminescence of meso-tetra-2-chlorophenylporphyrin.

Effects of solvent polarity on the photophysical behaviour of meso-tetra-2-chlorophenylporphyrin have been studied by means of steady-state absorption and fluorescence, as well as time-resolved fluorescence techniques. A non-mirror symmetric absorption and emission spectra due to vibronic borrowing were obtained. Time-resolved fluorescence study indicated the bi-exponential decay kinetics for both the emission bands, observed in steady-state emission spectra. Such findings implied that there exists two emitting species on the photoinduced conformational excursions of the excited-state equilibrium and also that their relative contributions to emission change with solvent polarity. Monte Carlo conformational search based on force-field molecular mechanics was performed to locate equilibrium conformers in the ground state which enable evaluation of the ground-state barrier energies. This was followed by CIS and ZINDO calculations to explore the excited-state barriers.

Ultrafast relaxation dynamics of the excited states of 1-amino- and 1-(N,N-dimethylamino)-fluoren-9-ones.

The dynamics of the excited states of 1-aminofluoren-9-one (1AF) and 1-(N,N-dimethylamino)-fluoren-9-one (1DMAF) are investigated by using steady-state absorption and fluorescence as well as subpicosecond time-resolved absorption spectroscopic techniques. Following photoexcitation of 1AF, which exists in the intramolecular hydrogen-bonded form in aprotic solvents, the excited-state intramolecular proton-transfer reaction is the only relaxation process observed in the excited singlet (S(1)) state. However, in protic solvents, the intramolecular hydrogen bond is disrupted in the excited state and an intermolecular hydrogen bond is formed with the solvent leading to reorganization of the hydrogen-bond network structure of the solvent. The latter takes place in the timescale of the process of solvation dynamics. In the case of 1DMAF, the main relaxation pathway for the locally excited singlet, S(1)(LE), or S(1)(ICT) state is the configurational relaxation, via nearly barrierless twisting of the dimethylamino group to form the twisted intramolecular charge-transfer, S(1)(TICT), state. A crossing between the excited-state and ground-state potential energy curves is responsible for the fast, radiationless deactivation and nonemissive character of the S(1)(TICT) state in polar solvents, both aprotic and protic. However, in viscous but strong hydrogen-bond-donating solvents, such as ethylene glycol and glycerol, crossing between the potential energy surfaces for the ground electronic state and the hydrogen-bonded complex formed between the S(1)(TICT) state and the solvent is possibly avoided and the hydrogen-bonded complex is weakly emissive.

Antimony(III) chloride catalyzed direct three component one-pot Mannich reaction.

Antimony(III) chloride catalyzes the three component Mannich type reaction of a variety of in-situ generated Schiff bases generated from aromatic aldehydes and anilines with cyclic/acyclic ketones. The reaction proceeds smoothly at ambient temperature to afford the corresponding beta-amino ketones in good yields with moderate to good diastereoselectivity.

Photophysical investigations on non-covalently linked fullerene/tetraarylporphyrin supramolecular complexes.

The host-guest interactions of various tetraarylporphyrins (TP), viz., 5,10,15,20-tetraphenyl-21H,23H-porphyrin (1), 5,10,15,20-tetrakis(octadecyloxyphenyl)-21H,23H-porphyrin (2) and 5,10,15,20-tetrakis(dodecyloxyphenyl)-21H,23H-porphyrin (3) with C60 and C70 have been studied by 1H NMR, UV-vis and fluorescence spectroscopic techniques in toluene medium. All the fullerene/porphyrin complexes are found to be stable with 1:1 stoichiometry. Binding constants (K) of all the fullerene/porphyrin complexes have been determined by fluorescence quenching experiment. The trend in K values revealed that the presence of long chain n-alkyl group in tetraarylporphyrin effectively and remarkably increases the selectivity ratio of C70 over C60. Theoretical calculations have extended a good support in interpreting the stability difference between various fullerene/TP complexes.

NMR spectrometric studies of complexation of [60]fullerene with series of meso-tetraphenylporphyrins.

Extensive 1H NMR spectrometric studies have been done to gain information on the nature of molecular interactions of the supramolecular complexes of [60]fullerene with a series of meso-tetraphenylporphyrins, namely, meso-5,10,15,20-tetraphenylporphyrin (1), meso-5,10,15,20-tetra-2-bromophenyl-porphyrin (2) and meso-5,10,15,20-tetra-2-chlorophenyl-porphyrin (3) in toluene medium. [60]Fullerene has been shown to form 1:1 adducts with the above series of meso-tetraphenylporphyrins. Formation constants (K) for all the complexes have been determined from the systematic variation of the NMR chemical shifts of beta proton of the porphyrin in presence of [60]fullerene. It has been observed that 3 acts as a better donor in forming supramolecular complex with [60]fullerene.