Green synthesis of heterocyclic alkenes using MCM 41 supported perchloric acid catalytic system: characterization and DFT studies.

CONTEXT: In this work, a series of heterocyclic alkenes were prepared by the reaction of 2-hydroxy-1-naphthaldehyde with various heterocyclic active methylene compounds via Knoevenagel condensation reaction using mesoporous silica, MCM 41, supported perchloric acid as an efficient green catalytic system under solvent-free conditions. A comparative study of the conventional method vs the green method was also reported with the same raw materials. 1H NMR, 13C NMR, IR, and mass spectroscopic techniques were used for the characterization of synthesized compounds. METHODS: Computational study was performed for these compounds by applying density functional theory (DFT) at M06 functional and 6-311G (d,p) basis set to interpret the electronic structures and counter check the experimental findings. The frequency analysis with aforementioned levels of DFT was performed to confirm the stability associated with optimized geometries. The true minimum for the optimized geometries for 1, 2, and 3 was achieved as indicated by the absence of negative eigenvalues in all the calculated frequencies. Additionally, natural bond orbitals (NBOs) and nonlinear optical (NLO) properties were explored utilizing the aforementioned level and basis set combination via DFT, whereas the frontier molecular orbitals (FMOs) evaluation was done at time-dependent density functional theory TDDFT at M06/6-311G(d,p). The global reactivity parameters were also calculated using the FMO data. These computation-based outcomes were found in good agreement with the experimental findings.

Synthesis and characterization of the new ligand, 1,2,4-triazino[5,6-b]indol-3-ylimino methyl naphthalene-2-ol and its Ni(II) and Cu(II) complexes: comparative studies of their in vitro DNA and HSA Binding.

A new ligand 1,2,4-triazino[5,6-b]indol-3-ylimino methyl naphthalene-2-ol (HL) was derived from 5H-[1,2,4]triazino[5,6-b]indol-3-amine and 2-hydroxy-1-naphthaldehyde. The metal complexes of the type [Ni(L)(Bipy)]1/2SO4 (1), [Cu(L)(Bipy)(H2O)2]1/2SO4 (2), [Ni(L)(Phen)]1/2SO4 (3) and [Cu(L)(Phen)(H2O)2]1/2SO4 (4) were synthesized. The ligand (HL) and complexes 1-4 were thoroughly characterized by elemental analysis and spectroscopic methods (FT-IR, ToF-MS, 1H NMR, 13C NMR), molar conductance and magnetic moment determination. The Ni(II) complexes 1 and 3 adopt the square planar geometry and Cu(II) complexes 2 and 4 acquire distorted octahedral arrangement. In vitro DNA binding behavior of ligand (HL) and metal complexes 1-4 was explored by fluorescence spectral and ethidium bromide studies. The outcomes reveal that the complexes interact with DNA via non-covalent groove binding and electrostatic interactions. The higher binding constant (K) values of 4.35 × 104 and 9.12 × 104 M-1 for complexes 2 and 4 indicate stronger binding ability with DNA. Moreover, in vitro human serum albumin (HSA) binding experiment with HL and complexes 1-4 reveals conformational modulations in the Trp-214 microenvironments in the subdomain IIA pocket.

A Quinoxaline-Naphthaldehyde Conjugate for Colorimetric Determination of Copper Ion.

This work facilitates detection of bivalent copper ion by a simple Schiff base probe QNH based on a quinoxaline-naphthaldehyde framework. The detailed study in absorption spectroscopy and theoretical aspects and crystal study of the probe and probe-copper complex has been discussed. The detection limit of the probe in the presence of Cu2+ is 0.45 µM in HEPES-buffer/acetonitrile (3/7, v/v) medium for absorption study. The reversibility of the probe-copper complex has been investigated by EDTA. The selective visual detection of copper has been established also in gel form.

Synthesis of Naphthalene-Based Polyaminal-Linked Porous Polymers for Highly Effective Uptake of CO2 and Heavy Metals.

Studying the effect of functional groups on the porosity structure and adsorption efficiency of polymer materials is becoming increasingly interesting. In this work, a novel porous polyaminal-linked polymer, based on naphthalene and melamine (PAN-NA) building blocks, was successfully synthesized by a one-pot polycondensation method, and used as an adsorbent for both CO2 and heavy metals. Fourier transform infrared spectroscopy, solid-state 13 C NMR, powder X-ray diffraction, and thermogravimetry were used to characterize the prepared polymer. The porous material structure was established by field-emission scanning electron microscope and N2 adsorption-desorption methods at 77 K. The polymer exhibited excellent uptake of CO2, 133 mg/g at 273 K and 1 bar. In addition, the adsorption behavior of PAN-NA for different metal cations, including Pb(II), Cr(III), Cu(II), Cd(II), Ni(II), and Ba(II), was investigated; a significant adsorption selectivity toward the Pb(II) cation was detected. The influence of pH, adsorbent dose, initial concentrations, and contact time was also assessed. Our results prove that the introduction of naphthalene in the polymer network improves the porosity and, thus, CO2 adsorption, as well as the adsorption of heavy metals.

Domino Transformations of Ene/Yne Tethered Salicylaldehyde Derivatives: Pluripotent Platforms for the Construction of High sp3 Content and Privileged Architectures.

Diversity-oriented synthesis (DOS) has become a powerful synthetic tool that facilitates the construction of nature-inspired and privileged chemical space, particularly for sp3 -rich non-flat scaffolds, which are needed for phenotypic screening campaigns. These diverse compound collections led to the discovery of novel chemotypes that can modulate the protein function in underrepresented biological space. In this context, starting material-driven DOS is one of the most important tools used to build diverse compound libraries with rich stereochemical and scaffold diversity. To this end, ene/yne tethered salicylaldehyde derivatives have emerged as a pluripotent chemical platform, the products of which led to the construction of a privileged chemical space with significant biological activities. In this review, various domino transformations employing o-alkene/alkyne tethered aryl aldehyde/ketone platforms are described and discussed, with emphasis on the period from 2011 to date.

Anticancer Function and ROS-Mediated Multi-Targeting Anticancer Mechanisms of Copper (II) 2-hydroxy-1-naphthaldehyde Complexes.

Multi-targeting of oncoproteins by a single molecule represents an effectual, rational, and an alternative approach to target therapy. We carried out a systematic study to reveal the mechanisms of action of newly synthesized Cu2+ compounds of 2-naphthalenol and 1-(((2-pyridinylmethyl)imino)methyl)- (C1 and C2). The antiproliferative activity of the as-synthesized complexes in three human cancer cell lines indicates their potential as multi-targeted antitumor agents. Relatively, C1 and C2 showed better efficacy in vitro relative to Cisplatin and presented promising levels of toxicity against A-549 cells. On the whole, the Cu2+ complexes exhibited chemotherapeutic effects by generating reactive oxygen species (ROS) and arresting the cell cycle in the G0/G1 phase by competent regulation of cyclin and cyclin-dependent kinases. Fascinatingly, the Cu2+ complexes were shown to activate the apoptotic and autophagic pathways in A-549 cells. These complexes effectively induced endoplasmic reticulum stress-mediated apoptosis, inhibited topoisomerase-1, and damaged cancer DNA through a ROS-mediated mechanism. The synthesized Cu2+ complexes established ROS-mediated targeting of multiple cell signaling pathways as a fabulous route for the inhibition of cancer cell growth.

[A new naphthaldehyde derivative from Comastoma pulmonarium and its anti-tobacco mosaic virus (anti-TMV) activity].

A new naphthaldehyde derivative has been isolated from Comastoma pulmonarium by using various chromatographic techniques, including silica gel, Sephadex LH-20, MCI-gel resin and RP-HPLC. This compounds was determined as 5-methoxy-2-methyl-7-(2-oxopropyl)naphthalene-1-carbaldehyde(1) by NMR, MS, IR and UV spectra. This compound was also evaluated for its anti-tobacco mosaic virus (anti-TMV) activity. The result showed that it showed high anti-TMV activity with inhibition rate of 32.8%. The inhibition rate is close to that of positive control (ningnanmycin).

A Dual-Target Fluorescent Probe with Response-Time Dependent Selectivity for Cd2+ and Cu2.

A novel fluorescent probe (NT) was developed by merging 2-hydrazinylbenzothiazole with 2-hydroxy-1-naphthaldehyde for the detection of Cd2+ and Cu2+. The probe alone is almost nonfluorescent due to the isomerization of C=N in the excited state. The addition of Cd2+ can cause an immediate strong green fluorescence owing to the suppression of C=N isomerization by Cd2+-coordination. Furthermore, NT gives a delayed turn-on fluorescence response to Cu2+ although it is a vigorous fluorescence quencher, which was thanks to the inhibition of the electron transfer between excited fluorophore and paramagnetic Cu2+ by sulfur donor. Based on fluorescence spectra and ESI-MS analysis, the binding modes between NT and Cd2+/Cu2+ were proposed.

A new naphthaldehyde derivative from Comastoma pulmonarium and its anti-tobacco mosaic virus (anti-TMV) activity / 中国中药杂志

A new naphthaldehyde derivative has been isolated from Comastoma pulmonarium by using various chromatographic techniques, including silica gel, Sephadex LH-20, MCI-gel resin and RP-HPLC. This compounds was determined as 5-methoxy-2-methyl-7-(2-oxopropyl)naphthalene-1-carbaldehyde(1) by NMR, MS, IR and UV spectra. This compound was also evaluated for its anti-tobacco mosaic virus (anti-TMV) activity. The result showed that it showed high anti-TMV activity with inhibition rate of 32.8%. The inhibition rate is close to that of positive control (ningnanmycin).

A highly selective and sensitive turn-on fluorescent probe for the detection of Al3+ and its bioimaging.

A novel fluorescent sensor, 1-((2-hydroxynaphthalen-1-yl)methylene)urea (ocn) has been designed and applied as a highly selective and sensitive fluorescent probe for recognition of Al3+ in Tris-HCl (pH = 7.20) solution. The probe ocn exhibits an excellent selectivity to Al3+ over other examined metal ions, anions and amino acids with a prominent fluorescence 'turn-on' at 438 nm. ocn binds to Al3+ with a 2:1 binding stoichiometry and the detection limit was 0.3 µM. Furthermore, its capability of biological application was evaluated and the results showed that the sensor could be used to detect Al3+ in living cells.

Metal Complexation Properties of Schiff Bases Containing 1,3,5-Triazine Derived from 2-Hydroxy-1-Naphthaldehyde in Solution. A Simple Spectrofluorimetric Method to Determine Mercury (II).

Four new Schiff base ligands carrying naphthalene groups were prepared from the reaction of 2,4-diamino-6-methyl-1,3,5-triazine and 2,4-diamino-6-undecyl-1,3,5-triazine with 2-hydroxy-1-naphthaldehyde. The influence of a series of metal ions including Cu2+, Co2+, Hg2+, Al3+, Cr3+, Fe3+, Pb2+, Ni2+, Cd2+, Zn2+, Mn2+, Ag+, Ba2+, Ca2+ and Mg2+ on the spectroscopic properties of the ligands was investigated by means of absorption and emission spectrometry. The results of spectrophotometric and spectrofluorimetric titrations disclosed the complexation stoichiometry and complex stability constant of the ligands with metal ions. A simple spectrofluorimetric method was developed using the Schiff base derived from 2,4-diamino-6-undecyl-1,3,5-triazine to determine Hg2+ ion. No cleanup or enrichment of the tap water sample was required. A modified standard addition method was used to eliminate matrix effect. The standard addition graph was linear between 0.2 and 2.6 mg/L in determination of Hg2+. Detection and quantification limits were 0.08 and 0.23 mg/L, respectively. The simple and cost-effective method can be applied to water samples.

Characterization of metabolites in rats after gavage of two lignans from fruits of Vitex negundo var. cannabifolia by UFLC-IT-TOF-MS / 中草药

Objective: To investigate in vivo metabolic profiles of two lignans, 6-hydroxy-4-(4-hydroxy-3-methoxyphenyl)-3- hydroxymethyl-7-methoxy-3,4-dihydro-2-naphthaldehyde (VB-1) and vitedoin A (VB-2) in the rats. Methods: A UFLC-IT- TOF-MS method was applied to characterize the prototypes and metabolites of VB-1 and VB-2 in rat feces, urine, bile, and plasma after oral administration. Results: Eleven metabolites of the two parent compounds were detected and two prototypes were identified unambiguously by comparing with references. Analysis of metabolites revealed that glucuronidation, sulfation, and hydroxylation were major biotransformation pathways of two lignans. Conclusion: In this study, under the analysis of metabolites of two lignans, its in vivo metabolic process is basically clarified. The results could be helpful for the further pharmacokinetics and pharmacological evaluations of VB-1 and VB-2.

A simple and sensitive method to analyze genotoxic impurity hydrazine in pharmaceutical materials.

Hydrazine (N2H4) is a known genotoxic impurity that typically needs to be controlled down to low ppm level in pharmaceutical development. Hydrazine, however, is a challenging molecule to analyze using conventional analytical techniques due to its physical and chemical properties (e.g. lack of chromophore, absence of any carbon atom, low molecular weight, high polarity and volatility). Additionally, analysis in pharmaceutical samples commonly encounters significant interference from matrix components that greatly overshadow the response of hydrazine. This work describes a simple, accurate and sensitive reversed-phase liquid chromatography-UV derivatization method for determination of trace amount hydrazine in pharmaceutical materials featuring three prominent strategies to address the problems associated with hydrazine analysis. First, the derivatization reaction attaches chromophores to hydrazine, which greatly increases its sensitivity by UV-vis detection. Secondly, the derivatization reaction generates a lambda max that is well-shifted away from the absorption wavelengths of pharmaceutical matrix interferences. Thirdly, from a separation standpoint, the derivatization further removes matrix interference effects through chromatography by achieving higher resolution of the derivative product from the active pharmaceutical ingredient (API) and its related impurities for accurate quantitation for trace level of genotoxic impurities (GTIs). 2-Hydroxy-1-Naphthalaldehyde (HNA) was chosen as the derivatizing reagent, and the resulting hydrazone product has a maximum UV absorbance at wavelength of 406/424nm which is in the visible range. Since most drug substance and impurities have UV absorbance ranging from 190 to 380nm, interference from the matrix was minimized and the appropriate selectivity was obtained, the detection limit is 0.25ppm (0.25µg/g API). This method was validated and applied as a generic method to determine hydrazine for pharmaceutical process control and drug material release.

Discovery and identification of 2-methoxy-1-naphthaldehyde as a novel strigolactone-signaling inhibitor.

Knowledge about strigolactone biosynthesis and signaling is increasing and the crystal structure of strigolactone receptor protein D14 has been resolved. Although a variety of strigolactone biosynthesis inhibitors and strigolactone agonists are known, no inhibitors of strigolactone signaling have been reported. Here, we conducted virtual screening in silico to identify chemical regulators that inhibit SL reception. We used LigandScout to analyze a pharmacophore model based on structural information about D14 protein and complex D14-D-OH (a hydrolysis product of strigolactone formed by D14). We identified a candidate compound, XM-47, and confirmed that it inhibits D14-SLR1 and D14-D53 interactions. A possible product of XM-47 hydrolysis, 2-methoxy-1-naphthaldehyde (2-MN), inhibits D14-SLR1 and D14-D53 interactions and restores the growth of rice tillering buds suppressed by strigolactone.

Crystal structure of 1,1'-{(pentane-1,5-di-yl)bis[(aza-niumylyl-idene)methanylyl-idene]}bis(naphthalen-2-olate).

The whole mol-ecule of the title compound, C27H26N2O2, is generated by twofold rotational symmetry, with the central C atom of the pentyl chain located on the twofold rotation axis. The compound crystallizes as a bis-zwitterion, and there are two intra-molecular N-H⋯O hydrogen bonds generating S(6) ring motifs. In the crystal, mol-ecules are linked by pairs of C-H⋯O hydrogen bonds, forming ribbons propagating along [001], and enclosing R 2 (2)(22) ring motifs.

A new polymorph of 1-({[1,3-dihy-droxy-2-(hy-droxy-meth-yl)propan-2-yl]iminio}meth-yl)naphthalen-2-olate.

The title compound, C15H17NO4, containing two mol-ecules in the asymmetric unit is a polymorph of the crystal structure published by Martínez et al. [(2011). Eur. J. Org. Chem. pp. 3137-3145] which at 120 K is monoclinic with one mol-ecule in the asymmetric unit. Both mol-ecules in the title compound are in the trans form. In the crystal, N-H⋯O and O-H⋯O hydrogen bonds connect mol-ecules, forming a two-dimensional network parallel to (001).

Crystal structure of 1,1'-{(dodecane-1,12-di-yl)bis-[(aza-niumylyl-idene)methanylyl-idene]}bis-(naphthalen-2-olate).

The title compound, C34H40N2O2, exists in an extended conformation and has crystallographically imposed centrosymmetry. The crystal packing can be described as being composed of parallel layers stacked along [010]. The zwitterionic structure is stabilized by an intra-molecular N-H⋯O hydrogen-bond inter-action.

Fluorescent imino and secondary amino chitosans as potential sensing biomaterials.

A variety of fluorescent imino and secondary amino chitosans were synthesized under very mild conditions by reaction of the biopolymer amino functions with aromatic aldehydes in an acidified methanolic suspension. Simultaneous reactions of several aldehydes with chitosan were successfully carried out, and kinetic studies showed that 1-pyrenecarboxaldehyde reacts the fastest among them. An unprecedented study on the evaluation of the degree of N-substitution (DS, ranging from 31.7% to 12.0%) for the chitosan Schiff bases by using solid state CPMAS (13)C NMR is performed. A linear correlation between the DS obtained for the secondary amino chitosans by (1)H NMR (55.3-10.2%) and those obtained by CPMAS (13)C NMR (34.4-13.8%) has allowed us to calculate an empirical correlation factor that could be applied on chitosan-based aromatic systems. The new chiral-labelled chitosan derivatives exhibit a stable fluorescent behaviour, which was used to explore solvent sensoring applications.

1,1'-{(Hexane-1,6-di-yl)bis-[(aza-niumylyl-idene)methanylyl-idene]}bis-(naphthalen-2-olate).

The whole molecule of the title Schiff base compound, C28H28N2O2, is generated by inversion symmetry. It is formed from two units of ortho-hy-droxy-naphthaldehyde bridged with 1,6-di-amino-hexane. The N atoms are protonated and, thus, the structure is a bis-zwitterionic compound in the solid state. The zwitterion shows strong intra-molecular N-H⋯O hydrogen bonds between the iminium N and the naphthaleno-late O atoms.

Molecular functions of the iron-regulated metastasis suppressor, NDRG1, and its potential as a molecular target for cancer therapy.

N-myc down-regulated gene 1 (NDRG1) is a known metastasis suppressor in multiple cancers, being also involved in embryogenesis and development, cell growth and differentiation, lipid biosynthesis and myelination, stress responses and immunity. In addition to its primary role as a metastasis suppressor, NDRG1 can also influence other stages of carcinogenesis, namely angiogenesis and primary tumour growth. NDRG1 is regulated by multiple effectors in normal and neoplastic cells, including N-myc, histone acetylation, hypoxia, cellular iron levels and intracellular calcium. Further, studies have found that NDRG1 is up-regulated in neoplastic cells after treatment with novel iron chelators, which are a promising therapy for effective cancer management. Although the pathways by which NDRG1 exerts its functions in cancers have been documented, the relationship between the molecular structure of this protein and its functions remains unclear. In fact, recent studies suggest that, in certain cancers, NDRG1 is post-translationally modified, possibly by the activity of endogenous trypsins, leading to a subsequent alteration in its metastasis suppressor activity. This review describes the role of this important metastasis suppressor and discusses interesting unresolved issues regarding this protein.