Binol quinone methides as bisalkylating and DNA cross-linking agents

The photogeneration and detection of new binol quinone methides undergoing mono- and bisalkylation of free nucleophiles was investigated by product distribution analysis and laser flash photolysis in water solution using binol quaternary ammonium derivatives 2 and 12 as photoactivated precursors. The alkylation processes of N and S nucleophiles are strongly competitive with the hydration reaction. DNA cross-linking potency of the water-soluble binol quaternary ammonium salt 2 was investigated as a pH function and compared to that of other quaternary ammonium salts capable of benzo-QM (QM = quinone methide) photogeneration by gel electrophoresis. DFT calculations in the gas phase and in water bulk on the binol and benzo quaternary ammonium salts 2 and 4 evidence structural and electrostatic features of the binol derivative which might offer a rationalization of its promising high photo-cross-linking efficiency.     

Water soluble extended naphthalene diimides as pH fluorescent sensors and G-quadruplex ligands

Extended naphthalene diimides (NDIs) fused to 1,4-dihydropyrazine-2,3-dione, containing two solubilizing moieties, have been synthesized. Fluorescence spectra of the new NDIs were remarkably affected by pH, as the second deprotonation of the dihydropyrazinedione moiety (pK(a) 6.9) switched off the emission. Binding to a G-quadruplex folded oligonucleotide and stoichiometry were evaluated by FRET melting assay and CD analysis. G-quadruplex binding was strongly enhanced shifting from pH 7.4 to pH 6.0 as a consequence of the dihydropyrazinedione moiety protonation. Cytotoxicity studies using two human telomerase-positive cell lines (HT29 and A549) revealed that the best G-quadruplex ligand was very active against the colon cell line, with an EC(50) of 300 nM.     

Core-tetrasubstituted naphthalene diimides: synthesis, optical properties, and redox characteristics

2,3,6,7-tetrabromonaphthalene dianhydride has been synthesized by the bromination of naphthalene dianhydride with dibromoisocyanuric acid in excellent yield. The condensation of this dianhydride with 2,6-diisopropylaniline yielded the corresponding tetrabromo-substituted naphthalene diimide (NDI), which is a versatile precursor for the synthesis of core-tetrafunctionalized NDIs. Nucleophilic substitution of tetrabromo NDI with alkoxy, alkylthio, and alkylamino nucleophiles afforded a series of core-tetrasubstituted NDI chromophores that complete the series of previously reported di- and trifunctionalized NDI derivatives. The effects of electronic nature and number of core substituents on the optical and electrochemical properties of NDIs have been investigated by UV-vis and fluorescence spectroscopy and cyclic voltammetry. The absorption maxima (629-642 nm) of tetraamino NDIs are strongly bathochromically shifted compared to those of other core-functionalized NDIs.     

Stannyl derivatives of naphthalene diimides and their use in oligomer synthesis

2-Stannyl and 2,6-distannyl naphthalene diimides (NDIs) can be synthesized through the palladium-catalyzed reaction of the appropriate bromo derivatives with hexabutylditin. The utility of these precursors in palladium catalyzed cross-coupling reactions is demonstrated by the synthesis of bi- and ter-NDI derivatives, UV-vis, cyclic voltammetry, and n-channel organic field-effect transistor data for which are compared to those of the monomeric parent NDI.     

Mechanisms of ferriheme reduction by nitric oxide: nitrite and general base catalysis

The reductive nitrosylation (Fe(III)(P) + 2NO + H(2)O = Fe(II)(P)(NO) + NO(2)(-) + 2H(+)) of the ferriheme model Fe(III)(TPPS) (TPPS = tetra(4-sulfonatophenyl)porphyrinato) has been investigated in moderately acidic solution. In the absence of added or adventitious nitrite, this reaction displays general base catalysis with several buffers in aqueous solutions. It was also found that the nitrite ion, NO(2)(-), is a catalyst for this reaction. Similar nitrite catalysis was demonstrated for another ferriheme model system Fe(III)(TMPy) (TMPy = meso-tetrakis(N-methyl-4-pyridyl)porphyrinato), and for ferriheme proteins met-hemoglobin (metHb) and met-myoglobin (metMb) in aqueous buffer solutions. Thus, it appears that such catalysis is a general mechanistic route to the reductive nitrosylation products. Two nitrite catalysis mechanisms are proposed. In the first, NO(2)(-) is visualized as operating via nucleophilic addition to the Fe(III)-coordinated NO in a manner similar to the reactions proposed for Fe(III) reduction promoted by other nucleophiles. This would give a labile N(2)O(3) ligand that hydrolyzes to nitrous acid, regenerating the original nitrite. The other proposal is that Fe(III) reduction is effected by direct outer-sphere electron transfer from NO(2)(-) to Fe(III)(P)(NO) to give nitrogen dioxide plus the ferrous nitrosyl complex Fe(II)(P)(NO). The NO(2) thus generated would be trapped by excess NO to give N(2)O(3) and, subsequently, nitrite. It is found that the nitrite catalysis rates are markedly sensitive to the respective Fe(III)(P)(NO) reduction potentials, which is consistent with the behavior expected for an outer-sphere electron-transfer mechanism. Nitrite is the product of NO autoxidation in aqueous solution and is a ubiquitous impurity in experiments where aqueous NO is added to an aerobic system to study biological effects. The present results demonstrate that such an impurity should not be assumed to be innocuous, especially in the context of recent reports that endogenous nitrite may play physiological roles relevant to the interactions of NO and ferriheme proteins.     

Enthalpy and entropy changes for the intercalation of small molecules to DNA. I. Substituted naphthalene monoimides and naphthalene diimides

Calorimetric studies have been performed on the intercalation of a series of nitro and amino substituted naphthalene monoimide cations to calf thymus DNA. For comparison, we also included in the study the unsubstituted naphthalene diimide dication. All of the substituted naphthalene monoimides formed dimers at the concentrations used in the calorimetric titrations, and dimerization constants for these compounds were derived from spectroscopic studies and used in calculating the H _B ^o parameters from the calorimetric data. The dimerization constants increase in the order 3-NO₂MI=4-NO₂MI>3-NH₂MI>4-NH₂MI. For the unsubstituted naphthalene monoimide and 3-NO₂MI and 4-NO₂MI, the H _B ^o parameters are within experimental error equal to that found for the naphthalene diimide, i.e., –4.3 kcal-mol^–1. Thus, changes in entropy cause the K _B for the diimide to be 40 times larger than that for the monoimide. This observation is consistent with the current electrostatic theory for counterion binding to DNA: a dication should cause the release of more counterions than a monocation and produce a more positive S _B ^o . For the amino substituted naphthalene monoimides, the K _B values are similar to the other monoimides, but H _B ^o =–6.7 kcal-mol^–1. We propose that a hydrogen bond is responsible for the unusual enthalpy and entropy effects seen for 3-NH₂MI and 4-NH₂MI.     

Fine-tuning the molecular energy levels by incorporating thiophene units onto the π-backbone of core-expanded naphthalene diimides

A series of core-expanded naphthalene diimides (NDI-DTYM) and thiophene-based derivatives (1a-c) were designed and synthesized to investigate the relationship between molecular structures and the highest occupied molecular orbital (HOMO) energy levels but has little impact on the lowest unoccupied molecular orbital (LUMO) energy levels. The results demonstrated that increasing the number of thiophene units can gradually elevate the HOMO energy levels but had little impact on the LUMO energy levels. The n-channel organic field-effect transistors (OFETs) based on 1b and 1c have demonstrated that these almost unchanged LUMO energy levels are proper to transport electrons.     

Novel catalysis of o-nitrophenyl carbonates by p-dimethlaminonopyridine

Transesterification reactions of o-nitrophenyl carbonates have been found to be greatly facilitated by use of p-dialkylaminopyridines as catalysts. A 20-fold rate increase is observed using 0.01 eq. of p-dimethylaminopyridine in place of 2.00 eq of triethylamine. Such rate enhancement is $\text{not}$ observed with p-nitrophenyl carbonates: 2.00 eq of Et₃N causes reaction to occur 8.5 times faster than 0.01 eq of DMAP. DMAP catalyzed reactions of o-nitrophenyl carbonate have been used to prepare aromatic carbonates of 0° in high yields, and avoid the necessity of using 2 equiv. of base.     

Proton reduction catalysis by manganese vinylidene and allenylidene complexes

The present paper reports the unprecedented observation of a catalytic electrochemical proton reduction based on metallocumulene complexes. Manganese phenylvinylidene (η⁵-C₅H₅)(CO)(PPh₃)MnCC(H)Ph (1) and diphenylallenylidene (η⁵-C₅H₅)(CO)₂MnCCCPh₂ (3) are shown to catalyze the reduction of protons from HBF₄ into dihydrogen in CH₂Cl₂ or CH₃CN media at −1.60 and −0.84 V (in CH₃CN) vs. Fc, respectively. The working potential for 3 (−0.84 V vs. Fc in CH₃CN) is the lowest reported to date for protonic acids reduction in non-aqueous media. The similar catalytic cycles disclosed here include the protonation of 1, 3 into the carbyne cations [(η⁵-C₅H₅)(CO)(PPh₃)MnC-CH₂Ph]BF₄ ([2]BF₄), [(η⁵-C₅H₅)(CO)₂MnC-CHCPh₂]BF₄ ([4]BF₄) followed by their reduction to the corresponding 19-electron radicals 2, 4, respectively. Both carbyne radicals undergo a rapid homolytic cleavage of the C_β-H bond generating an H-radical producing molecular hydrogen with concomitant recovery of the neutral metallocumulenes thereby completing a catalytic cycle.     

Synthesis of naphthalene and indene precursors to naphthoic and indenoic acids

As part of ongoing research to investigate structural requirements for lactate dehydrogenase inhibition by highly substituted naphthoic and indenoic acids, certain naphthalene and indene precursors to those types of compounds are required. Described here are efficient preparations of 1-naphthoic acid precursors 6-benzyl-2,3-dimethoxy-1-propylnaphthalenes, including compounds with substituted benzyl groups and 7-benzyl-2,3-dimethoxy-1-propylnaphthalene. Also described are the syntheses of indenoic acid precursors 2-benzyl-5,6-dimethoxy-7-propyl-1H-indenes, including compounds with substituted benzyl groups. These compounds were made from the key intermediates 6,7-dimethoxy-5-propyl-1-tetralone, 6,7-dimethoxy-8-propyl-1-tetralone, and 5,6-dimethoxy-4-propyl-1-indanone.     

Lewis base catalysis by thiourea: N-bromosuccinimide-mediated oxidation of alcohols

In recent times, (thio)urea derivatives have become synonymous with hydrogen bonding owing to their extensive applicability as small molecule organocatalysts. In this paper, another activation mode by thiourea derivatives, namely via Lewis base catalysis, is disclosed for the NBS-mediated oxidation of alcohols. The mild reaction conditions employed here is suitable for chemoselective oxidation of secondary alcohol in the presence of primary alcohol.     

Homochiral crystallization of microporous framework materials from achiral precursors by chiral catalysis

While it is not uncommon to form chiral crystals during crystallization, the formation of bulk porous homochiral materials from achiral building units is rare. Reported here is the homochiral crystallization of microporous materials through the chirality induction effect of natural alkaloids. The resulting material possesses permanent microporosity and has a uniform pore size of 9.3 A.     

Selective sensing of Cu2+ ion by naphthalene based Schiff base

Research is going on to synthesize materials for acting as sensors of metal ions and are also published in different journals but the cause for sensing has not been clearly explained. In this paper, the reason for selective sensing of Cu²⁺ ions has been explained. A novel Schiff base fluorescent probe 3-[(2-hydroxy-naphthalen-1-ylmethylene)-hydrazono]-butan-2-one oxime (NPTH) was designed and synthesized to use as Cu²⁺ sensor. From our recent experiments, it has been found that only Cu²⁺ among different metal ions has been sensed by the synthesized ligand. The reason for selection and sensing of Cu²⁺ by the ligand was established by different spectroscopic techniques. The detection limit of NPTH was calculated as low as 4.11 ​× ​10^-4M for Cu²⁺. Therefore, these results indicate that sensor NPTH has great prospective to detect Cu²⁺ ion in environmental analysis systems. Density functional theory (DFT) calculations have been done to ascertain the ground state geometry of NPTH.     

Synthesis and evaluation of polyacrylamides derived from polycyclic pendant naphthalene,indole, and phenothiazine based chalcone moiety as potent antimicrobial agents

Polycyclic chalcone‐containing polyacrylamides, namely, poly ((N‐(4‐((E)‐3‐(naphthalen‐6‐yl)‐3‐oxoprop‐1‐enyl) phenyl) acrylamide), poly((N‐(4‐((E)‐3‐(1H‐indol‐3‐yl)‐3‐oxoprop‐1‐enyl) phenyl) acrylamide), and poly((N‐(4‐((E)‐3‐oxo‐3‐(10H‐phenothiazin‐8‐yl) prop‐1‐enyl) phenyl) acrylamide), were synthesized by Claisen–Schmidt condensation reaction, followed by ultrasonic irradiation reduction. The synthesized polymers were characterized by Fourier transform infrared spectroscopy, ¹H nuclear magnetic resonance, and ¹³C nuclear magnetic resonance spectroscopic technique. The newly synthesized polymers have been screened for antibacterial and antifungal activities by using resazurin reduction assay method, and the resulting polyacrylamides showed promising activity against various tested bacteria and fungi. Among the polymers, poly((N‐(4‐((E)‐3‐oxo‐3‐(10H‐phenothiazin‐8‐yl) prop‐1‐enyl) phenyl) acrylamide) and poly((N‐(4‐((E)‐3‐(1H‐indol‐3‐yl)‐3‐oxoprop‐1‐enyl) phenyl) acrylamide) exhibited better antifungal and antibacterial activities than poly ((N‐(4‐((E)‐3‐(naphthalen‐6‐yl)‐3‐oxoprop‐1‐enyl) phenyl) acrylamide), whereas all the polymers do not show any sign of antibacterial and antifungal activity against Streptococcus faecalis and Candida glabrata. Copyright © 2016 John Wiley & Sons, Ltd.     

An efficient reduction of nitro and bromine naphthalene derivatives

Russian Journal of General Chemistry - Reduction of 1,5-dimethoxy-4-nitronaphthalene by hydrazine hydrate was optimized in the course of current study. Influence of metals, temperature and solvents...     

Diastereoselective synthesis of polyfunctionalized piperidines as precursors of dopamine transporter imaging agents

The design and synthesis of a new kind of precursors of radiolabelled tracer agents for dopamine transporters imaging is described. The concept is based on the possibility of introducing the radioelement far from the sites of recognition and on the fact that only the labelled marker could cross the blood brain barrier to reach the dopamine transporters. For this purpose, a polyfunctionalized piperidine was synthesized bearing two aldehyde functions in the configuration allowing the formation of a tropane analog after the introduction of complexing moieties and complexation of a radioactive metal.     

Novel spirobisindanes for use as precursors to polymers of intrinsic microporosity

The synthesis of novel spirobisindane-based monomers for the preparation of polymers of intrinsic microporosity (PIMs) with bulky, rigid substituents is described. Polymers derived from monomers containing spiro-linked fluorene substituents display enhanced solubility and microporosity due to additional frustration of packing in the solid state.     

Biomimetic oxidation of 3,5-di-tert-butylcatechol by dioxygen via Mn-enhanced base catalysis

The 6-coordinate dioximatomanganese(II) complex [Mn(HL)(CH3OH)]+ (2, where H2L is [HON=C(CH3)C(CH3)=NCH2CH2]2NH), formed by instant solvolysis of [Mn2(HL)2](BPh4)2 (1) in methanol, accelerates the triethylamine (TEA)-catalyzed oxidation of 3,5-di-tert-butylcatechol (H2dtbc) by O2 to the corresponding o-benzoquinone. Significantly, 2 alone has no catalytic effect. The observed rate increase can be explained by the interaction of 2 with the hydroperoxo intermediate HdtbcO2- formed from Hdtbc- and O2 in the TEA-catalyzed oxidation. The kinetics of the TEA-catalyzed and Mn-enhanced reaction has been studied by gas-volumetric monitoring of the amount of O2 consumed. The initial rate of O2 uptake (V(in)) shows a first-order dependence on the concentration of 2 and O2 and saturation kinetics with respect to both H2dtbc and TEA. The observed kinetic behavior is consistent with parallel TEA-catalyzed and Mn-enhanced oxidation paths. The 3,5-di-tert-butylsemiquinone anion radical is an intermediate detectable by electron spin resonance (ESR) spectroscopy. The dimeric catalyst precursor has been characterized by X-ray diffraction and electrospray ionization mass spectrometry and the monomeric catalyst by ESR spectroscopy.     

Copper-thioguanine metallodrug with self-reinforcing circular catalysis for activatable MRI imaging and amplifying specificity of cancer therapy

For chemotherapy, drug delivery systems often suffer from the inefficient drug loading capability, which usually cause systems toxicity and extra burden to excrete carrier itself. Moreover, the cancer therapeutic efficacy is also greatly limited by the specificity of tumor microenvironment for reactive oxygen species(ROS) based cancer therapeutic strategy(e.g., chemodynamic therapy). Herein, we have developed metal-drug coordination nanoplatform that can not only be responsive to tumor microenvironment but also modulate it, so as to achieve efficient treatment of cancer. Excitingly, by employing small molecule drug(6-thioguanine) as ligand copper ions, we achieve a high drug loading rate(60.1%) and 100% of utilization of metal-drug coordination nanoplatform(Cu-TG). Interestingly, Cu-TG possessed high-efficiently horseradish peroxidase-like, glutathione peroxidase-like and catalase-like activity. Under the tumor microenvironment, Cu-TG exhibited the self-reinforcing circular catalysis that is able to amplify the cellular oxidative stress, inducing notable cancer cellular apoptosis. Moreover, Cu-TG could be activated with glutathione(GSH) and facilitated for GSH triggered 6-TG release, higher selective therapeutic effect toward cancer cells, and GSH activated T_1 weight-magnetic resonance imaging. Based on the above properties, Cu-TG exhibited magnetic resonance imaging(MRI) guiding, efficient and synergistic combination of chemodynamic and chemotherapy with self-reinforcing therapeutic outcomes in vivo.