A comprehensive study on the photophysical and non-linear optical properties of thienyl-chalcone derivatives.

The impact of the substitutional position of the chorine atom on the non-linear optical (NLO) response of chalcone derivatives is reported in this paper. Two thienyl-chalcone derivatives, (E)-3-(2,4-dichloro-phenyl)-1-(2,5-dichlorothiophen-3-yl)prop-2-en-1-one (3A25D2) and (E)-3-(2,6-dichloro-phenyl)-1-(2,5-dichlorothiophen-3-yl)prop-2-en-1-one (3A25D4), are synthesized, and their crystal structures were determined by single-crystal X-ray diffraction analysis. The photophysical and third-order NLO properties of 3A25D2 and 3A25D4 were investigated experimentally and computationally. The third-order NLO properties of 3A25D2 and 3A25D4 dissolved in N,N-dimethylformamide (DMF) were studied using Z-scan technique with 800 nm, 70 femtosecond (fs) pulses, and 532 nm continuous wave (CW) laser excitation. Closed aperture data recorded with fs pulses revealed positive non-linearity of both the compounds, while a strong negative non-linearity was observed in the CW regime. Open aperture data revealed that both the compounds exhibit positive non-linear absorption in fs pulsed and CW domains. Several wave function analysis methods, such as the inter-fragment charge transfer (IFCT) analysis, hole-electron analysis, (hyper)polarizability density analysis, and decomposition of the (hyper)polarizability contribution by numerical integration, were carried out to study the optical properties and charge transfer mechanism. In addition, the influence of the medium (liquid and crystalline) and external field wavelength on the optical properties of the two molecules were analyzed. Thermal and electronic contributions toward NLO properties were studied experimentally. The theoretically calculated cubic hyperpolarizability γ(-ω; ω, ω, -ω) in liquid for 3A25D2 and 3A25D4 were 4.69 × 10-34 and 2.68 × 10-34 esu, whereas the corresponding femtosecond regime Z-scan results gave 4.35 × 10-34 and 3.78 × 10-34 esu, respectively.

New 3-O-substituted xanthone derivatives as promising acetylcholinesterase inhibitors.

A new series of 3-O-substituted xanthone derivatives were synthesised and evaluated for their anti-cholinergic activities against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). The results indicated that the xanthone derivatives possessed good AChE inhibitory activity with eleven of them (5, 8, 11, 17, 19, 21-23, 26-28) exhibited significant effects with the IC50 values ranged 0.88 to 1.28 µM. The AChE enzyme kinetic study of 3-(4-phenylbutoxy)-9H-xanthen-9-one (23) and ethyl 2-((9-oxo-9H-xanthen-3-yl)oxy)acetate (28) showed a mixed inhibition mechanism. Molecular docking study showed that 23 binds to the active site of AChE and interacts via extensive π-π stacking with the indole and phenol side chains of Trp86 and Tyr337, besides the hydrogen bonding with the hydration site and π-π interaction with the phenol side chain of Y72. This study revealed that 3-O-alkoxyl substituted xanthone derivatives are potential lead structures, especially 23 and 28 which can be further developed into potent AChE inhibitors.

Design, Synthesis and Docking Studies of Flavokawain B Type Chalcones and Their Cytotoxic Effects on MCF-7 and MDA-MB-231 Cell Lines.

Flavokawain B (1) is a natural chalcone extracted from the roots of Piper methysticum, and has been proven to be a potential cytotoxic compound. Using the partial structure of flavokawain B (FKB), about 23 analogs have been synthesized. Among them, compounds 8, 13 and 23 were found in new FKB derivatives. All compounds were evaluated for their cytotoxic properties against two breast cancer cell lines, MCF-7 and MDA-MB-231, thus establishing the structure-activity relationship. The FKB derivatives 16 (IC50 = 6.50 ± 0.40 and 4.12 ± 0.20 µg/mL), 15 (IC50 = 5.50 ± 0.35 and 6.50 ± 1.40 µg/mL) and 13 (IC50 = 7.12 ± 0.80 and 4.04 ± 0.30 µg/mL) exhibited potential cytotoxic effects on the MCF-7 and MDA-MB-231 cell lines. However, the methoxy group substituted in position three and four in compound 2 (IC50 = 8.90 ± 0.60 and 6.80 ± 0.35 µg/mL) and 22 (IC50 = 8.80 ± 0.35 and 14.16 ± 1.10 µg/mL) exhibited good cytotoxicity. The lead compound FKB (1) showed potential cytotoxicity (IC50 = 7.70 ± 0.30 and 5.90 ± 0.30 µg/mL) against two proposed breast cancer cell lines. It is evident that the FKB skeleton is unique for anticancer agents, additionally, the presence of halogens (Cl and F) in position 2 and 3 also improved the cytotoxicity in FKB series. These findings could help to improve the future drug discovery process to treat breast cancer. A molecular dynamics study of active compounds revealed stable interactions within the active site of Janus kinase. The structures of all compounds were determined by ¹H-NMR, EI-MS, IR and UV and X-ray crystallographic spectroscopy techniques.

Cholinesterase Inhibitory Activities of Adamantyl-Based Derivatives and Their Molecular Docking Studies.

Adamantyl-based compounds are clinically important for the treatments of type 2 diabetes and for their antiviral abilities, while many more are under development for other pharmaceutical uses. This study focused on the acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities of adamantyl-based ester derivatives with various substituents on the phenyl ring using Ellman's colorimetric method. Compound 2e with a 2,4-dichloro electron-withdrawing substituent on the phenyl ring exhibited the strongest inhibition effect against AChE, with an IC50 value of 77.15 µM. Overall, the adamantyl-based ester with the mono-substituent at position 3 of the phenyl ring exhibited good AChE inhibition effects with an ascending order for the substituents: Cl < NO2 < CH3 < OCH3. Furthermore, compounds with electron-withdrawing groups (Cl and NO2) substituted at position 3 on their phenyl rings demonstrated stronger AChE inhibition effects, in comparison to their respective positional isomers. On the other hand, compound 2j with a 3-methoxyphenyl ring showed the highest inhibition effect against BChE, with an IC50 value of 223.30 µM. Molecular docking analyses were conducted for potential AChE and BChE inhibitors, and the results demonstrated that the peripheral anionic sites of target proteins were predominant binding sites for these compounds through hydrogen bonds and halogen interactions instead of hydrophobic interactions in the catalytic active site.

An azodye-rhodamine-based fluorescent and colorimetric probe specific for the detection of Pd(2+) in aqueous ethanolic solution: synthesis, XRD characterization, computational studies and imaging in live cells.

Azodye-rhodamine hybrid colorimetric fluorescent probe (L) has been designed and synthesized. The structure of L has been established based on single crystal XRD. It has been shown to act as a selective turn-on fluorescent chemosensor for Pd(2+) with >40 fold enhancement by exhibiting red emission among the other 27 cations studied in aqueous ethanol. The coordination features of the species of recognition have been computationally evaluated by DFT methods and found to have a distorted tetrahedral Pd(2+) center in the binding core. The probe (L) has been shown to detect Pd up to 0.45 µM at pH 7.4. Furthermore, the probe can be used to image Pd(2+) in living cells.

Cd(2+) Triggered the FRET "ON": A New Molecular Switch for the Ratiometric Detection of Cd(2+) with Live-Cell Imaging and Bound X-ray Structure.

On the basis of the Förster resonance energy transfer mechanism between rhodamine and quinoline-benzothiazole conjugated dyad, a new colorimetric as well as fluorescence ratiometric probe was synthesized for the selective detection of Cd(2+). The complex formation of the probe with Cd(2+) was confirmed through Cd(2+)-bound single-crystal structure. Capability of the probe as imaging agent to detect the cellular uptake of Cd(2+) was demonstrated here using living RAW cells.

Synthesis, molecular structure and spectroscopic investigations of novel fluorinated spiro heterocycles.

This paper describes an efficient and regioselective method for the synthesis of novel fluorinated spiro-heterocycles in excellent yield by cascade [5+1] double Michael addition reactions. The compounds 7,11-bis(4-fluorophenyl)-2,4-dimethyl- 2,4-diazaspiro[5.5] undecane-1,3,5,9-tetraone (3a) and 2,4-dimethyl-7,11-bis (4-(trifluoromethyl)phenyl)-2,4-diazaspiro[5.5]undecane-1,3,5,9-tetraone (3b) were characterized by single-crystal X-ray diffraction, FT-IR and NMR techniques. The optimized geometrical parameters, infrared vibrational frequencies and NMR chemical shifts of the studied compounds have also been calculated using the density functional theory (DFT) method, using Becke-3-Lee-Yang-Parr functional and the 6-311G(d,p) basis set. There is good agreement between the experimentally determined structural parameters, vibrational frequencies and NMR chemical shifts of the studied compounds and those predicted theoretically. The calculated natural atomic charges using NBO method showed higher polarity of 3a compared to 3b.The calculated electronic spectra are also discussed based on the TD-DFT calculations.

Synthesis and Crystallographic Insight into the Structural Aspects of Some Novel Adamantane-Based Ester Derivatives.

Adamantyl-based compounds are commercially important in the treatments for neurological conditions and type-2 diabetes, aside from their anti-viral abilities. Their values in drug design are chronicled as multi-dimensional. In the present study, a series of 2-(adamantan-1-yl)-2-oxoethyl benzoates, 2(a-q), and 2-(adamantan-1-yl)-2-oxoethyl 2-pyridinecarboxylate, 2r, were synthesized by reacting 1-adamantyl bromomethyl ketone with various carboxylic acids using potassium carbonate in dimethylformamide medium at room temperature. Three-dimensional structures studied using X-ray diffraction suggest that the adamantyl moiety can serve as an efficient building block to synthesize 2-oxopropyl benzoate derivatives with synclinal conformation with a looser-packed crystal packing system. Compounds 2a, 2b, 2f, 2g, 2i, 2j, 2m, 2n, 2o, 2q and 2r exhibit strong antioxidant activities in the hydrogen peroxide radical scavenging test. Furthermore, three compounds, 2p, 2q and 2r, show good anti-inflammatory activities in the evaluation of albumin denaturation.

Benzofuranyl Esters: Synthesis, Crystal Structure Determination, Antimicrobial and Antioxidant Activities.

A series of five new 2-(1-benzofuran-2-yl)-2-oxoethyl 4-(un/substituted)benzoates 4(a-e), with the general formula of C8H5O(C=O)CH2O(C=O)C6H4X, X = H, Cl, CH3, OCH3 or NO2, was synthesized in high purity and good yield under mild conditions. The synthesized products 4(a-e) were characterized by FTIR, ¹H-, (13)C- and ¹H-(13)C HMQC NMR spectroscopic analysis and their 3D structures were confirmed by single-crystal X-ray diffraction studies. These compounds were screened for their antimicrobial and antioxidant activities. The tested compounds showed antimicrobial ability in the order of 4b < 4a < 4c < 4d < 4e and the highest potency with minimum inhibition concentration (MIC) value of 125 µg/mL was observed for 4e. The results of antioxidant activities revealed the highest activity for compound 4e (32.62% ± 1.34%) in diphenyl-2-picrylhydrazyl (DPPH) radical scavenging, 4d (31.01% ± 4.35%) in ferric reducing antioxidant power (FRAP) assay and 4a (27.11% ± 1.06%) in metal chelating (MC) activity.

Nanomolar detection of hypochlorite by a rhodamine-based chiral hydrazide in absolute aqueous media: application in tap water analysis with live-cell imaging.

By employing the oxidation property of hypochlorite (OCl(-)), a novel rhodamine-based hydrazide of the chiral acid ((S)-(-)-2-pyrrolidone-5-carboxylic acid) (RHHP) was designed and synthesized for detection of OCl(-) absolutely in aqueous medium at nanomolar level. The structure of the chiral sensor was also proved by the X-ray crystallography. The bioactivity and the application of the probe for detection of OCl(-) in natural water system have been demonstrated. A plausible mechanism for oxidation of the sensor followed by hydrolysis is also proposed. The sensibility of the receptor toward OCl(-) was studied in absolute aqueous media, and the detection limit of hypochlorite-mediated oxidation to the receptor in nanomolar level makes this platform (RHHP) an ultrasensitive and unique system for OCl(-) oxidation.

2-[(E)-2-(4-Eth-oxy-phen-yl)ethen-yl]-1-methyl-quinolinium 4-fluoro-benzene-sulfonate.

In the structure of the title salt, C20H20NO(+)·C6H4FO3S(-), the 4-(eth-oxy-phen-yl)ethenyl unit is disordered over two positions with a refined site-occupancy ratio of 0.610 (6):0.390 (6). The cation is nearly planar, the dihedral angle between the quinolinium and benzene rings being 6.7 (4) and 1.7 (7)° for the major and minor components, respectively. The eth-oxy group is essentially coplanar with the benzene ring [C-O-C-Cmethy = 177.1 (8) and 177.8 (12)° for the major and minor components, respectively]. In the crystal, cations and anions are linked into chains along the b-axis direction by C-H⋯Osulfon-yl weak inter-actions. These chains are further connected into sheets parallel to (001) by C-H⋯Osulfon-yl weak inter-actions. The chains are also stacked along the a axis through π-π inter-actions involving the quinolinium and benzene rings [centroid-centroid distances = 3.636 (5) Šfor the major component and 3.800 (9) Šfor the minor component]. C-H⋯π inter-actions are also present.

(E)-2-[(2,4,6-Tri-meth-oxy-benzyl-idene)amino]-phenol.

There are two independent mol-ecules in the asymmetric unit of the title compound, C16H17NO4, with similar conformations but some differences in their bond angles. Each mol-ecule adopts a trans configuration with respect to the methyl-idene C=N bond and is twisted with a dihedral angle between the two substituted benzene rings of 80.52 (7)° in one mol-ecule and 83.53 (7)° in the other. All meth-oxy groups are approximately coplanar with the attached benzene rings, with Cmeth-yl-O-C-C torsion angles ranging from -6.7 (2) to 5.07 (19)°. In the crystal, independent mol-ecules are linked together by O-H⋯N and O-H⋯O hydrogen bonds and a π-π inter-action [centroid-centroid distance of 3.6030 (9) Å], forming a dimer. The dimers are further linked by weak C-H⋯O inter-actions and another π-π inter-action [centroid-centroid distance of 3.9452 (9) Å] into layers lying parallel to the ab plane.

(E)-2-[4-(Di-ethyl-amino)-styr-yl]-1-methyl-quinolin-1-ium 4-chloro-benzene-sulfonate monohydrate.

The asymmetric unit of the title hydrated salt, C22H25N2 (+)·C6H4ClO3S(-)·H2O, comprises two 2-[4-(di-ethyl-amino)-styr-yl]-1-methyl-quinolin-1-ium cations, two 4-chloro-benzene-sul-fon-ate anions and two solvent water mol-ecules. One ethyl group of both cations displays disorder over two positions in a 0.659 (2):0.341 (2) ratio in one mol-ecule and in a 0.501 (2):0.499 (2) ratio in the other. The sulfonate group of one anion is also disordered over two positions in a 0.893 (7):0.107 (7) ratio. The dihedral angle between the mean plane of the quinolinium ring system and that of benzene ring is 10.57 (18)° in one cation and 14.4 (2)° in the other. In the crystal, cations, anions and water mol-ecules are linked into chains along the [010] direction by O-H⋯Osulfonate hydrogen bonds, together with weak C-H⋯Osulfonate and C-H⋯Cl inter-actions. The cations are stacked by π-π inter-actions, with centroid-centroid distances in the range 3.675 (2)-4.162 (3) Å.

Trichodermaerin: a diterpene lactone from Trichoderma asperellum.

The title compound, C20H28O3, known as 'trichodermaerin' [systematic name: (4E)-4,9,15,16,16-penta-methyl-6-oxa-tetra-cyclo-[10.3.1.0(1,10).0(5,9)]hexa-dec-4-ene-7,13-dione], is a diterpene lactone which was isolated from Trichoderma asperellum. The structure has a tetra-cycic 6-5-7-5 ring system, with the cyclo-hexa-none ring adopting a twisted half-chair conformation and the cyclo-pentane ring adopting a half-chair conformation, whereas the cyclo-heptene and tetra-hydro-furan-anone rings are in chair and envelope (with the methyl-substituted C atom as the flap) conformations, respectively. The three-dimensional architecture is stabilized by C-H⋯O inter-actions.

(E)-4-Meth-oxy-N'-(2,4,5-tri-meth-oxy-benzyl-idene)benzohydrazide hemihydrate.

The title compound crystallizes as a hemihydrate, C18H20N2O5·0.5H2O. The mol-ecule exists in an E conformation with respect to the C=N imine bond. The 4-meth-oxy-phenyl unit is disordered over two sets of sites with a refined occupancy ratio of 0.54 (2):0.46 (2). The dihedral angles between the benzene rings are 29.20 (9) and 26.59 (9)°, respectively, for the major and minor components of the 4-meth-oxy-substituted ring. All meth-oxy substituents lie close to the plane of the attached benzene rings [the Cmeth-yl-O-C-C torsion angles range from -4.0 (12) to 3.9 (2)°]. In the crystal, the components are linked into chains propagating along [001] via N-H⋯O and O-H⋯O hydrogen bonds and weak C-H⋯O inter-actions.

6-Cyanona-phthalen-2-yl 4-hexyl-benzo-ate.

In the title compound, C24H23NO2, a whole mol-ecule is disordered over two sets of sites with occupancies in a ratio of 0.692 (6):0.308 (6). In the major disorder component, the naphthalene ring system forms a dihedral angle of 68.6 (5)° with the benzene ring. The corresponding angle in the minor component is 81.6 (10)°. In the crystal, mol-ecules are linked into chains propagating along the b-axis direction via weak C-H⋯O hydrogen bonds. The crystal packing is further consolidated by weak C-H⋯π inter-actions.

6-(Hex-5-en-yloxy)naphthalene-2-carb-oxy-lic acid.

The asymmetric unit of the title compound, C17H18O3, comprises three independent mol-ecules with similar geometries. In each mol-ecule, the carbonyl group is twisted away from the napthalene ring system, making dihedral angles of 1.0 (2), 1.05 (19)° and 1.5 (2)°. The butene group in all three mol-ecules are disordered over two sets of sites, with a refined occupancy ratio of 0.664 (6):0.336 (6). In the crystal, mol-ecules are oriented with respect to their carbonyl groups, forming head-to-head dimers via O-H⋯O hydrogen bonds. Adjacent dimers are further inter-connected by C-H⋯O hydrogen bonds into chains along the a-axis direction. The crystal structure is further stabilized by weak C-H⋯π inter-actions.

Crystal structure of (E)-4-{2-[4-(all-yloxy)phen-yl]diazen-yl}benzoic acid.

The title compound, C16H14N2O3, has an E conformation about the azo-benzene [-N=N- = 1.2481 (16) Å] linkage. The benzene rings are almost coplanar [dihedral angle = 1.36 (7)°]. The O atoms of the carb-oxy-lic acid group are disordered over two sets of sites and were refined with an occupancy ratio of 0.5:0.5. The two disordered components of the carb-oxy-lic acid group make dihedral angles of 1.5 (14) and 3.8 (12)° with the benzene ring to which they are attached. In the crystal, mol-ecules are linked via pairs of O-H⋯O hydrogen bonds, forming inversion dimers. The dimers are connected via C-H⋯O hydrogen bonds, forming ribbons lying parallel to [120]. These ribbons are linked via C-H⋯π inter-actions, forming slabs parallel to (001).

Photoinduced reactions of para-quinones with bicyclopropylidene leading to diverse polycyclic compounds with spirocyclopropanes.

Photoinduced reactions of bicyclopropylidene (BCP) with para-quinones (p-quinones) including benzoquinones, naphthoquinones, and anthraquinones were found to proceed via different cycloaddition pathways and lead to diverse polycyclic products bearing spiropropyl moiety. Photocycloaddition of BCP with benzoquinones gave spirooxetanes as the primary products, which upon irradiation were able to rearrange into the spiro[4.5]deca-6,9-diene-2,8-diones as secondary photoproducts. Chemoselectivity of the photocycloaddition of BCP with naphthoquinones relies largely on the substitution groups linked to the C═C in between the two carbonyl groups to give different types of products. Photoreaction of BCP with 9,10-anthraquinone gave not only the spirooxetane product, but also a novel spiro[indan-1,1'-phthalan]-3'-one product whose formation might be initiated by a transannular attack of the C4 cyclopropyl radical to the para-carbonyl group. Mechanisms involved in the formation of diverse primary or secondary products in the photoreactions of BCP with p-quinones were proposed. Some of the photoreactions also hold potentials as useful synthetic protocols for important spiropolycyclic compounds such as sesquiterpenes.

Photocycloadditions of substituted oxazoles with isoquinoline-1,3,4-trione--chemo-, regio-, diastereoselectivities and transformation of the photocycloadducts.

Photoreactions of isoquinoline-1,3,4-triones and oxazoles with different substituents were found to give different chemo-, regio- and diastereoselectivities. The substituent at the C5 on the oxazole ring showed great influence on the chemoselectivity of the photoreaction as well as on the transformation of the photocycloadducts. The 2-methyl-5-methoxyoxazoles reacted with isoquinoline-1,3,4-triones rapidly and gave spirooxetanes with high regio- and diastereo-selectivity. Diastereoselectivity in the reaction of 2-phenyl-5-methoxyoxazoles with isoquinoline-1,3,4-triones was relevant to the substituent on the 4-position on the oxazole ring. Replacement of the 5-methoxy group with 5-methyl or 5-phenyl resulted in significant decrease on the reactivity of the oxazole as well as change on the diastereoselectivity in photocycloaddition with isoquinoline-1,3,4-triones. Acid-mediated transformations of the photocycloadduct spirooxetanes was found to give different type of products including ß-hydroxy-α-aminocarbonyl compounds and spiroisoquinolineoxazolines under different reaction conditions. Substituents on the spirooxetanes as well as the type and amount of acid used in the reaction played important roles in determining the type and diastereoselectivity of the products in the transformations.