Sunita Salunke-Gawali

Benzo[α]phenoxazines and benzo[α]phenothiazine from vitamin K3: synthesis, molecular structures, DFT studies and cytotoxic activity

Synthesis and characterization of fluorescent benzo[α]phenoxazines viz., M-1B (10-chloro-6-methyl-7a,11a-dihydro-5H-benzo[α]phenoxazin-5-one), M-2B 6,10-dimethyl-7a,11a-dihydro-5H-benzo[α]phenoxazin-5-one), M-3B (6-methyl-7a,11a-dihydro-5H-benzo[α]phenoxazin-5-one) and benzo[α]phenthiazine, M-4B (6-methyl-5H-benzo[α]phenothiazin-5-one) were carried out. 1H and 13C chemical shifts were assigned from the 2DgHSQCAD NMR experiments. Compound M-1B crystallizes in the orthorhombic space group P212121, while M-2B and M-4B crystallize in the monoclinic space group P21/c. The crystal network of M-1B showed slipped π–π stacking and Cl⋯Cl interactions, while M-2B facilitated ladder like π–π stacked polymeric chains. The C⋯S contacts were observed in the crystal environment of M-4B. All these structures possess C–H⋯O interactions. Electronic structure and charge distribution in terms of molecular electrostatic potential and frontier orbital analyses based on the MO6-2X based density functional theory further showed that monomer and dimer structures are in keeping with the single crystal X-ray data and provide insights for the growth of the crystal network. Antiproliferative activity of M-1B–M-4B was determined from the MTT assay against a human breast adenocarcinoma cell line (MCF-7), human carcinoma cell line (HeLa) and normal skin cell line. All these compounds showed significant cytotoxic activity against MCF-7 and HeLa by inducing apoptosis and thus can be viewed as potential candidates for antitumor therapy. Compounds M-2B and M-4B were further found to be topoisomerase II inhibitors.

Separation and isolation of tautomers of 2-hydroxy-4-naphthoquinone-1-oxime derivatives by liquid chromatography: Antiproliferative activity and DFT studies

AbstractReversed phase HPLC separation and isolation of isomers of 2-hydroxy-4-naphthoquinone-1-oxime (Lwox) and 3-methyl-2-hydroxy-4-naphthoquinone-1-oxime (Phox) have been investigated. Two distinct peaks are observed in the chromatogram of Lwox and are assigned to ‘para’ tautomer; 2-hydroxy-4-naphthoquinone-1-oxime (3) and ‘ortho’ tautomer; 4-hydroxy-2-naphthoquinone-1-oxime (4). The tautomeric equilibrium of 3 and 4 has been manipulated by incrementally increasing the pH of the mobile phase from 2.5 to 10.5, and altering the solvent polarity. At pH > 6.8 the tautomers are well-separated from each other. There is no separation of Phox isomers between pH 2.5 and 10.5. Isolation of the tautomers has been carried out by preparative HPLC, with 3 and 4 obtained as ammonium bicarbonate adducts and characterized by LC-MS, FT-IR, and UV-visible spectroscopy. Red-orange 3 is characterized by a paranaphthoquinone stretch at 1287 cm−1 and a charge transfer band at 420 nm; yellow 4 exhibits, a similar stretch at 1246 cm−1 and absorption band at 406 nm. Compounds 3 and 4 were screened for selective antiproliferative activity in three cancer cell lines of different tissue types (COLO 205 (human colorectal adenocarcinoma), U87 MG (glioblastoma astrocytoma) and MIAPaCa-2 (human pancreatic carcinoma). Geometry-optimized structures for tautomers 3 and 4 (3′ and 4′ in Phox) were computed using the B3LYP method. Structures, 3 and 3′ are 4.7 and 5.8 kcal mol−1 more stabilized than 4 and 4′, respectively, as a result of a hydrogen bond interaction between the 2-hydroxyl group and the nitrogen of the oxime. FigureReversed phase chromatographic separation and isolation of tautomers of naphthoquinoneoximes is studied. Geometryoptimized structures for tautomers were computed using the B3LYP method. The separated tautomers are screened for cytotoxicity in three cancer cell lines COLO 205 (human colorectal adenocarcinoma), U87 MG (glioblastoma astrocytoma) and MIAPaCa-2 (human pancreatic carcinoma).

Dye sensitized solar cell with lawsone dye using a ZnO photoanode: experimental and TD-DFT study

The spectral features of lawsone (2-hydroxy-1,4-naphthoquinone), an active component of the natural dye henna, are analyzed in ethanol using experimental and computational methods. The calculated UV-Vis absorption spectrum from the time-dependent density functional theory (TD-DFT) approach is compared with the experimental results, allowing a detailed assignment of the UV-Vis spectral features based on molecular orbitals. Further, we have analyzed the light intensity dependent J–V characteristics and electrochemical impedance spectrum of a dye sensitized solar cell fabricated with lawsone and a ZnO photoanode. The photovoltaic data of the sensitizer adsorbed on ZnO films exhibited a reasonable power conversion efficiency, i.e. 0.68% at 26 mW cm−2 light intensity.

Lawsone Sensitized ZnO Photoelectrodes for Dye Sensitized Solar Cells

Innovations in materials technology in the fields of photovoltaics play an important role in the paradigm shift from fossil fuels to renewable energy sources. The use of solar energy is one of the most important problems in energy utilization. Dye sensitized solar cell (DSSC) technology has been recognized as a competitor to the well developed thin film solar cells. In the present investigation, we have fabricated a device using natural Lawsone (Heena) dye which was used to sensitize zinc oxide (ZnO) films. ZnO seed layer was deposited using chemical bath deposition and slurry was used to deposit ZnO films followed by sintering at 450°C for 30 minutes in air. Performance of nanostructure ZnO photoelectrode using lawsone dye as a function of residence time in the dye solution was studied. For 20 hour dye loading time, we were observed power conversion efficiency around 0.5% which is more as compared to 5 and 14 hours dye loading time.

Targeting a chemorefractory COLO205 (BRAF V600E) cell line using substituted benzo[α]phenoxazines

Mutational activations of the oncogene BRAF (especially BRAF V600E) result in a poor prognosis for colon cancer patients and are associated with chemoresistance rendering them refractory to treatment. The development of novel bioactive compounds with specific targeting abilities under such conditions is an urgent need in drug discovery. In this report we synthesize and characterize three fluorescent benzo[α]phenoxazine compounds (10R-benzo[α]phenoxazine-5-one, 1B; R = Cl, 2B; R = CH3, 3B; R = H) and their anticancer activities are evaluated in a COLO205 cell line. All three compounds with a logP value around 2 were cell permeable. However, 2B and 3B showed specific cytotoxicity in a malignant COLO205 cell line with a BRAF mutation (V600E) in comparison to a non-malignant wild-type BRAF HEK293T cell line. From further cell-based assays (cell cycle analysis, DNA fragmentation and caspase activation), we conclude that 2B and 3B treatment-induced selective cell death by inducing cell cycle arrest at the G0/G1 phase and caspase-mediated apoptosis (activation of the intrinsic and extrinsic pathways) are present only in BRAF V600E COLO205 cells. Further studies in the drug discovery pipeline might help develop these benzo[α]phenoxazines as promising chemotherapeutics for such refractory mutated cancers.

Bromine substituted aminonaphthoquinones: synthesis, characterization, DFT and metal ion binding studies

Bromine substituted aminonaphthoquinone ligands viz. 2-(2′-aminomethylpyridyl)-3-bromo-naphthalene-1,4-dione; (2MPA), 2-(3′-aminomethylpyridyl)-3-bromo-naphthalene-1,4-dione; (3MPA), 2-(2′-aminoethylpyridyl)-3-bromo-naphthalene-1,4-dione; (2EPA) and 2-(2′-aminomethylthiophenyl)-3-bromo-naphthalene-1,4-dione (2AMT) and 2-(2′-aminoethylthiophenyl)-3-bromo-naphthalene-1,4-dione (2AET) have been synthesized and characterized by single-crystal X-ray diffraction experiments in conjunction with long range corrected density functional theory. The heterocyclic amines on the naphthoquinone ring render diverse crystal structures. It has been shown that bromine substitution influences the planarity and mutual orientation of naphthoquinone and heterocycles in aminonaphthoquinone ligands. The 2MPA, 3MPA, 2EPA, 2AET aminonaphthoquinone ligands crystallize in the monoclinic space group whereas 2AMT led to the triclinic space group P. Furthermore, molecular packing of 2MPA and 2EPA revealed dimeric structures while 3MPA and 2AMT are rendered with ‘stair-case’ arrangements of molecules. 2AET, when viewed down c-axis, showed a ‘butterfly like’ arrangement. A broad charge transfer band (400–600 nm) was observed in the UV-visible spectra of these ligands. Besides 2MPA and 2EPA exhibit remarkable selectivity toward Cu2+ ions, accompanied by a color change from orange to blue in methanol and methanol–water mixture.

Regioselective synthesis of a vitamin K3 based dihydrobenzophenazine derivative: its novel crystal structure and DFT studies

A novel acid catalyzed regioselective Michael addition of o-phenylenediamine to vitamin K3 has been carried out to synthesize a dihydrobenzophenazine derivative viz. 6a-methyl-6a,7-dihydrobenzo[α]phenazin-5(6H)-one (1). The compound has been characterized using the single crystal X-ray diffraction and density functional theory.

Temperature Effect on Ancillary μ‐Carbonato Ligand Modes in Hydroxy Naphthoquinonato Copper(II) Complex: An EPR Spectroscopic and Magnetic Coupling Evidences

Thermal, magnetic and electrochemical properties of the complex 1, [Cu2 (μ‐CO3) (ONQ)2 (4HNQ)2] are discussed [where ONQ=2‐oxido‐1, 4‐napthoquinone and 4HNQ=4‐hydroxy‐1, 2‐naphthoquinone]. The coordination of the ligand is in tautomeric forms viz. ONQ and 4HNQ in 1. The carbonate anion acts as a bridge between two Cu (II) centers showing bidentate (μ‐η1‐η1‐CO3 2‐) coordination mode with distorted square based pyramidal geometry for each Cu(II) ion. Temperature‐dependent zero field splitting (zfs) interactions (D and E) are resolved from X‐ (300K and 77 K) and Q‐band (300K) EPR spectra. At 300K, E>D and at 77K, D>E. It reveals temperature dependent modes of coordination viz. syn‐anti and anti‐anti of ancillary ligand in 1. Variable temperature magnetic susceptibility (SQUID) measurements show a weak antiferromagnetic coupling between the two Cu (II) centers. The susceptibility data was best fitted with HDVV model and the coupling constant found to be J=−4.8 cm−1 with agreement factor R=2.41*10−8. Metal based redox couple assigned at E½=+0.18 V with ΔE=0.125 V corresponds to two electrons transfer in the Cu (II)⇔Cu (0) redox couple.

Thermal and spectral properties of alkali metal complexes of vitamin K3 analogue phthiocol

Abstract Hydroxynaphthoquinones, alkali, and alkali metal salts were used to synthesize several biologically important molecules. As hydroxynaphthoquinones act also as potential ligands, it is possible that alkali metal complexes may be formed as intermediates in such reactions. To ensure this, the reactions of 2-hydroxy-3-methyl-1,4-naphthoquinone (phthiocol, a vitamin K3 analogue) with sodium metal, alkali such as NaOH and KOH, and alkali metal salts such as CH3COONa, Na2CO3 and K2CO3 were studied in the present investigation. The products were characterized by various analytical techniques, namely elemental analysis, FT-IR, 1H NMR, UV–Vis, thermogravimetric (TG) analysis, GC–MS, and DSC studies. 100 % reduction of the ligand was observed in Phth-1 with sodium metal as reducing agent. The solution of CH3COONa, NaOH, KOH, and K2CO3 in methanol facilitates the reduction of phthiocol ligand. The reduction of the ligands may be probably due to disproportionate reaction of the ‘catechol’ form and the fully oxidized naphthoquinone form of the ligand. The radical signatures of the ligands in complexes were detected by EPR studies and also by carbonyl frequencies in FT-IR spectra. Non-isothermal TG studies confirm the presence of adsorbed and coordinated water molecules. Residue formed after complete decomposition was observed to be 1/2 Na2O in Phth-1 to Phth-3, K2O in Phth-4, and 1/2 K2O in Phth-5. Based on GC–MS and TG studies, three decomposition mechanisms are being proposed for all complexes.

Naphthoquinone based chemosensors for transition metal ions: experiment and theory

The synthesis and characterization of 2-((pyridine-2-yl)methylamino)naphthalene-1,4-dione (H-1), 2-((thiophen-2-yl)methylamino)naphthalene-1,4-dione (H-2) and 2-((pyridine/thiophen-2-yl)ethylamino)naphthalene-1,4-dione (H-3 and H-4) have been carried out. Molecular recognition abilities of these ligands toward transition metal ions in methanol, methanol–water, methanol–triethylamine or methanol–water–triethylamine mixtures, stoichiometries and association constants of H-1 and H-3 have been determined. It has been shown that H-1 and H-3 coordinate to metal ions via two nitrogen atoms and oxygen and exhibit remarkable selectivity towards Cu2+ ions in methanol or methanol–water mixtures, the complexation being accompanied by a color change from orange to intense blue. LOD (Limit of Detection) of Cu2+ with H-1, H-3 are 1.48 × 10−8 mol L−1 and 1.59 × 10−8 mol L−1 respectively. The vibrational spectra, 1H NMR chemical shifts and optical properties of H-1 to H-4 derived from density functional theory are also presented.