Synthesis,DFT calculations,cyclic voltammetry and antibacterial activities of a new blue-violet dye and a new blue-green fluorescent heterocyclic system

The new blue-violet dye 2-(3-hydroxyimino-2,3-dihydroimidazo[1,2-a]pyridin-2-yliden)-2-(2-thienyl)acetonitrile was prepared in high yield from the reaction of 3-nitroimidazo[1,2-a]pyridine with 2-(2-thienyl)acetonitrile by nucleophilic substitution of hydrogen. Acylation of the hydroxyl group led to a new heterocyclic system, (pyrido[2′,1′:2,3] imidazo[4,5-b]thieno[2,3-e]pyridine-11-carbonitrile) with very strong blue-green fluorescent properties. Physical, spectral and analytical data have confirmed the structures of the synthesized dyes. The optical and solvatochromic properties of these compounds were investigated and showed interesting photophysical properties. Density functional theory calculations of blue-violet and fluorescent dyes were performed to provide the optimized geometries, Mulliken atomic charges, relevant frontier orbitals and the prediction of ¹H NMR chemical shifts. The electrochemical properties of these dyes were investigated by cyclic voltammetry and an oxidation wave was observed at a half-wave potential of −0.143 V versus SCE for the blue-violet dye. Also, these new compounds exhibited potent antibacterial activity against Gram positive and negative bacterial species.     

Synthesis, characterization and crystal structures of boron-containing intermediates in the reductive amination of ferrocenecarboxaldehyde to a bis(ferrocenylmethyl) amine

Reaction of ferrocenecarboxaldehyde with aqueous methylamine leads to [(methylimino)methyl]ferrocene, which is reduced to N-(ferrocenylmethyl)-N-methylamine by NaBH₄. This amine reacts with ferrocenecarboxaldehyde and NaCNBH₃ to give the tertiary ammonium salt, di(N-(ferrocenylmethyl))-N-methylammonium cyanoborohydride. Hydrolysis of the NaCNBH₃ reaction mixture produces the free amine, di(N-(ferrocenylmethyl))-N-methylamine. Thermolysis of di(N-(ferrocenylmethyl))-N-methylammonium cyanoborohydride in refluxing tetrahydrofuran converts it to the cyanoborane adduct, di(N-ferrocenylmethyl)-N-methylamine-cyanoborane, with elimination of H₂. The new compounds are fully characterized by using spectroscopic and physical methods, including X-ray crystal structure determinations of di(N-(ferrocenylmethyl))-N-methylammonium cyanoborohydride, di(N-(ferrocenylmethyl))-N-methylamine, and di(N-(ferrocenylmethyl))-N-methylamine-cyanoborane.     

2- and 2,7-Substituted para-N-Methylpyridinium Pyrenes: Syntheses,Molecular and Electronic Structures,Photophysical, Electrochemical,and Spectroelectrochemical Properties and Binding to Double-Stranded (ds) DNA

Two N-methylpyridinium compounds and analogous N-protonated salts of 2- and 2,7-substituted 4-pyridyl-pyrene compounds were synthesised and their crystal structures, photophysical properties both in solution and in the solid state, electrochemical and spectroelectrochemical properties were studied. Upon methylation or protonation, the emission maxima are significantly bathochromically shifted compared to the neutral compounds, although the absorption maxima remain almost unchanged. As a result, the cationic compounds show very large apparent Stokes shifts of up to 7200 cm⁻¹. The N-methylpyridinium compounds have a single reduction at ca. −1.5 V vs. Fc/Fc⁺ in MeCN. While the reduction process was reversible for the 2,7-disubstituted compound, it was irreversible for the mono-substituted one. Experimental findings are complemented by DFT and TD-DFT calculations. Furthermore, the N-methylpyridinium compounds show strong interactions with calf thymus (ct)-DNA, presumably by intercalation, which paves the way for further applications of these multi-functional compounds as potential DNA-bioactive agents.     

Synthesis and biological evaluations of some Schiff-base esters of ferrocenyl aniline and simple aniline

The synthesis and biological studies of some long chain esters containing Schiff bases and their ferrocenyl analogues were carried out. The 4-amino ferrocene was prepared by the reported method. Long chain esters were synthesized by the condensation of different aliphatic acids with the corresponding aldehyde. The esters were then reacted with aniline as well as with 4-aminophenyl ferrocene to give corresponding Schiff bases. All the synthesized compounds were analyzed by elemental, FTIR and proton NMR studies, were also investigated for a range of biological activities. Determined by crown gall tumor inhibition assay. Antioxidant and DNA protective activities were determined by DPPH free radical scavenging assay and OH radical induced oxidative DNA damage assay, respectively. Among all test compounds, o-hydroxy-p-n-octadecanoyloxy-benzylidine-p-ferrocenyl aniline (FA2.1: a ferrocene containing Schiff base) showed highest antitumor, DPPH free radical scavenging and DNA protective activities.     

Synthesis, structure and redox potentials of biologically active ferrocenylalkyl azoles

The syntheses, structures, electrochemical properties of the series of ferrocenylalkyl azoles, FcAlkAz, as well as the antitumor activity of ferrocenylmethyl benzimidazole (8) have been studied. Above mentioned compounds were investigated by the method of cyclic voltametry. All of them exhibited a reversible one-electron oxidation-reduction wave owing to the ferrocene-ferrocenium redox couple with a positive shift (0.50-0.65 V) compared with that of ferrocene (0.42 V). The X-ray determination of molecular structures of 1-(ferrocenylmethyl)imidazole (4), 1-(ferrocenylbenzyl)imidazole (7) and 1-(ferrocenylmethyl)bezimidazole (8) was carried out. Compound 4 with imidazolyl substituent was found to be present in N-protonated form. Antitumor activity of 1-(ferrocenylmethyl)benzimidazole (8) against some solid tumor models such as adenocarcinoma 755 (Ca755), melanoma B16 (B16) and Lewis lung carcinoma was studied. The antitumor activity of compound 8 was compared with cisplatin effectiveness against some experimental tumor systems.     

Synthesis,spectral, electrochemical and magnetic properties of new symmetrical and unsymmetrical dinuclear copper(II) complexes derived from binucleating ligands with phenol and benzimidazole donors

New symmetrical 2,6-bis{N-[2-(2-benzimidazolyl)-phenyl]iminomethyl}-4-methylphenol (L¹) and unsymmetrical 2-N-[2-(2-benzimidazoyl)phenyl]iminomethyl-6-[(4-methylpiperazin-1-yl)-methyl]-4-methylphenol (L²) binucleating ligands have been synthesized. Complexation of these ligands with Cu(II) perchlorate and appropriate sodium salt offered the binuclear copper(II) complexes, [Cu₂L(X)](ClO₄)₂, (X=Cl, OH and OAc 1–6). Their spectral, electrochemical and magnetic properties have been studied. Two distinct reduction peaks were observed at negative potentials. The electrochemical data shows that the complexes of L² undergo reduction at less negative potential (E¹_pc=−0.15 to −0.25 V, E²_pc=−0.45 to −0.65 V) when compared to the complexes of L¹ (E¹_pc=−0.45 to −0.58 V, E²_pc=−1.07 to −1.103 V). A variable temperature magnetic study on the complexes of the ligand L¹ showed strong antiferromagnetic coupling between the copper atoms (−2J=285–295 cm⁻¹), in contrast, the complexes of the ligand L² showed weak antiferromagnetic interaction (−2J=60–85 cm⁻¹). Electron spin resonance (ESR) spectra (RT) of the complexes of ligand L¹ showed no signal and the complexes of ligand L² showed a broad feature.     

Solid-state electrolytes based on ionic network polymers

Interpenetrating and semi-interpenetrating polymer networks are synthesized with the use of cationic and anionic ionic monomers: N-[3-(methacryloyloxy)propyl]-N-methylpyrrolidinium bis(trifluoromethane-sulfonyl)imide, N-[2-(2-(2-(methacryloyloxy)ethoxy)ethoxy)ethyl]-N-methylpyrrolidinium bis(fluorosulfonyl)imide, and (N-butyl-N-methylpyrrolidinium 1-[3-(methacryloyloxy)propylsulfonyl] (trifluoromethanesulfonyl) imide. Their ionic conductivities, electrochemical stabilities, heat resistances, thermal stabilities, and mechanical properties and the swelling of the films in ionic liquid/lithium salt mixtures were studied. The copolymerization of N-[2-(2-(2-(methacryloyloxy)ethoxy)ethoxy)ethyl]-N-methylpyrrolidinium bis(fluorosulfonyl)imide and poly(ethylene glycol dimethacrylate) and poly(ethylene glycol methacrylate) in the presence of butadiene-acrylonitrile rubber and a solution of Li(CF₃SO₂)₂N in N-(methoxymethyl)-N-methylpyrrolidinium bis(fluorosulfonyl)imide yielded a solid-state electrolyte with a set of properties optimum among the studied films: an ionic conductivity of 1.3 × 10^?4S/cm (25°C), a tensile strength of 80 kPa, and an elongation at break of 60%.     

Synthesis and electrochemical studies of disubstituted ferrocene/dipeptide conjugates with sulfur-containing side chains

A series of 1,1′-disubstituted ferrocenoyl peptides incorporating dipeptide sidearms has been synthesized and studied electrochemically. The target peptides include ferrocene as an electrochemical reporter, sulfur-containing amino acids (l-methionine, S-methyl-l-cysteine, S-trityl-l-cysteine, S-benzhydryl-l-cysteine) as metal binding agents, and amino acids with non-polar side chains (l-alanine, l-valine, l-phenylalanine) as spacers between reporter and metal binding groups. Ferrocene/dipeptide conjugates were prepared using solution phase peptide synthesis methods employing a BOC-protecting group strategy and HBTU- (O-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate) mediated peptide coupling. The electrochemical properties of these 1,1′-substituted ferrocenoyl peptides have been characterized using cyclic voltammetry. All exhibit fully reversible one electron oxidation steps; forward sweep half wave peaks (E_F), reverse sweep half wave peaks (E_R), peak separations (ΔE_P) and half wave potentials (E_1/2) are reported. Finally, towards the goal of utilizing ferrocenoyl peptides to detect heavy metals in solution, the response of these ferrocene/dipeptide conjugates to metal cations (zinc(II), mercury(II), cadmium(II), lead(II), silver(I)) has been examined. Monitoring changes in the potential of the Fe(II)/Fe(III) redox couple to follow peptide/metal interactions, we have probed the influence of the spacer unit between the redox reporter and the metal-binding amino acid, and shown that these systems respond to mercury(II) more strongly than to other heavy metal ions.     

Synthesis of photolabile o-nitroveratryloxycarbonyl (NVOC) protected peptide nucleic acid monomers

The chemical synthesis of peptide nucleic acid (PNA) monomers was accomplished using various combinations of the o-nitroveratryloxycarbonyl (NVOC) group (N-aminoethylglycine backbone) and base labile acyl-type nucleobase protecting groups (anisoyl for adenine and cytosine; isobutyryl for guanine), thus offering a photolithographic solid-phase PNA synthetic strategy compatible with photolithographic oligonucleotide synthesis conditions and allowing the in situ synthesis of PNA microarrays in an essentially neutral medium, by avoiding the use of the commonly used deprotection reagents such as trifluoroacetic acid or piperidine. Convenient methods were also explored to prepare 1-(carboxymethyl)-4-N-(4-methoxybenzoyl)cytosine and 9-(carboxymethyl)-2-N-(isobutyryl)guanine with good yields.     

Synthesis, characterization and antitumor activity of 1,2-disubstituted ferrocenes and cyclodextrin inclusion complexes

Seven different ferrocene derivatives have been tested in vitro against Ehrlich ascites tumor cells. Neither ferrocene nor the monosubstituted derivative N,N-dimethylaminomethylferrocene showed cytotoxic activity (IC₅₀ > 1000 μM for 3 h treatments). Better results were obtained with 1,2-disubstituted derivatives. The IC₅₀ values ranged from 376.6 μM for 1,2-diformylferrocene to 71.2 μM for racemic 2-(N,N-dimethylaminomethyl)ferrocenecarboxamide. The latter derivative was also encapsulated in native β-cyclodextrin (CD), heptakis-2,3,6-tri-O-methyl-β-CD (TRIMEB) and 2-hydroxypropyl-β-CD (HPβCD) to give 1:1 (host:guest) inclusion compounds. The existence of true inclusion complexes in the solid state was confirmed by a combination of powder X-ray diffraction, thermogravimetric analysis, FTIR and ¹³C CP MAS NMR spectroscopy. The IC₅₀ value for the β-CD inclusion compound was identical to that obtained for the nonincluded ferrocene derivative. By contrast, the inclusion compounds comprising TRIMEB and HPβCD yielded IC₅₀ values of 25.2 and 20.0 μM, respectively. No obvious relationship could be established between the redox behavior of the compounds determined by cyclic voltammetry and the biochemical data.     

Synthesis and antioxidative activity of N,N-diethylthiocarbamate-containing 1,2-aminopropanethiols

Method for synthesis of S-(1,2-epithiopropyl)-N,N-diethylthiocarbamate, which is a key compound for production of various aryl-substituted 1,2-aminopropanethiols, was developed. The antioxidative activity of the compounds synthesized was studied.     

Novel redox receptors for ion-pair and α-amino acid: synthesis and complexation properties of calix[4]arene derivatives bearing large conjugated ferrocene groups

By reacting calix[4]arene 1,3-bi-hydrazide derivative (2) with formacylferrocene in “1?+?2” condensation mode, novel calix[4]arene derivative bearing two conjugated ferrocene groups (3) was obtained in yield of 88%. By reacting 1,3-bi-substituted [2-(p-formylphenyloxy)ethyloxy]-p-tert-butylcalix[4]arene (5) with 1,1′-diacetylferrocene hydrazone (4) in “1?+?1” condensation mode, novel calix[4]arene derivative with 1,3-substituted large conjugated ferrocene bridge (6) was synthesized in yield of 83%. The structures and conformations of new compounds were confirmed by elemental analyses, IR spectra, ESI-MS, ¹H NMR, etc. The electrochemical cyclic voltammetry experiments revealed that compounds 3 and 6 possessed excellent reversible electrochemical properties. The ¹H NMR titration study showed that compound 6 possessed excellent complexation abilities for NaH₂PO₄ and glycine in 1:1 host–guest complex with the association constants of 3,850 and 2,460?M^?1, respectively.     

Development in synthesis and electrochemical properties of thienyl derivatives of carbazole

A convenient and higher yielding synthetic route to N-alkyl-bis(thiophene)- and N-alkyl-bis(ethylenedioxythiophene) carbazole derivatives is reported and their aggregation, and electrochemical properties are characterized. The key step in the synthesis of this group of compounds has been the Stille-type coupling reaction between the N-alkyldibromocarbazole and tin derivatives of thiophene or ethylenedioxythiophene, as the best way for preparation of conjugated N-alkylcarbazole derivatives. For this group of compounds we also present an electrochemical polymerization effect.     

N 7-DNA: Base-Pairing Properties of N 7-(2′-Deoxy-β-D-erythro-pentofuranosyl)-Substituted Adenine,Hypoxanthine, and Guanine in Duplexes with Parallel Chain Orientation

Oligonucleotides containing N ⁷-(2′-deoxy-β-D -erythro-pentofuranosyl)adenine ( 1 ), -hypoxanthine ( 2 ), and -guanine ( 3 ) were synthesized on solid-phase using phosphonate and phosphoramidite chemistry. As part of the synthesis of compound 2 , the nucleobase-anion glycosylation of various 6-alkoxypurines with 2-deoxy-3,5-di-O-(4-toluoyl)-α-D -erythro-pentofuranosyl chloride ( 5 ) was investigated. The duplex stability of oligonucleotides containing N ⁷-glycosylated purines opposite to regular pyrimidines was determined, and thermodynamic data were calculated from melting profiles. Oligodeoxyribonucleotide duplexes containing N ⁷-glycosylated adenine⋅T_d or N ⁷-glycosylated guanine⋅C_d base pairs are more stable in the case of parallel strand orientation than in the case of antiparallel chains.     

Synthesis,characterization, and properties of novel bis(aryl)carbazole-containing N-coumarin derivatives

A series of novel N-coumarin derivatives containing oligothiophene-substituted N-coumarins as the core and bis(aryl)carbazoles as the substituent were synthesized and characterized. Their optical, electrochemical, and thermal properties were investigated. The electroluminescence (EL) properties of the selected materials were also studied. Solution-processed OLEDs with green and yellow light emission, turn-on voltages of 2.7–2.9 V, and maximum luminance efficiencies of up to 3.94 cd A⁻¹ at 17.6 mA cm⁻² (maximum power efficiency of 1.62 lm W⁻¹) were prepared.     

A novel synthesis of 4,5-diaryl-6-arylamino-2,3-benzo-1,3a,6a-triazapentalenes

Treatment of N-alkyl- and N-aryl-imines of 2,3-diaryl- and 2-alkyl-3-aryl-3-(benzotriazol-1-yl)propenals with trifluoroacetic anhydride in THF at room temperature gave 5-alkyl-4-aryl-6-[N-alkyl (and aryl)-N-trifluoroacetyl]amino-2,3-benzo-1,3a,6a-triazapentalenes in moderate to good yields. On heating triazapentalenes having R²=aryl in MeOH at reflux, detrifluoroacetylation of triazapentalene occurred to give title compounds in good yields. However, the same treatment of triazapentalenes having R²=alkyl did not give the corresponding detrifluoroacetylation product. The title compounds and 5-alkyl-4-aryl-6-(N-alkyl-N-trifluoroacetyl)amino-2,3-benzo-1,3a,6a-triazapentalenes were found to be good precursors for the synthesis of 1-(o-aminophenyl)-3-arylamino-4-alkyl (and aryl)-5-arylpyrazoles and 1-(o-aminophenyl)-3-(N-alkyl-N-trifluoroacetyl)amino-4-alkyl (and aryl)-5-arylpyrazoles, respectively.     

A convenient synthesis of the cytidyl 3′-terminal monomer for solid-phase synthesis of RNG oligonucleotides

Replacing the phosphodiester backbone of RNA with positively charged guanidinium linkages has been shown to enable RNA oligomers to overcome electrostatic repulsion and bind double-stranded DNA in a triplex with high affinity. Ribonucleotide monomers with the ability to form guanidinium linkages have been synthesized for the generation of ribooligonucleotides with guanidinium linkages (RNGs) through solid-phase synthesis. We report herein an efficient method for the synthesis of N⁴-benzoyl-2′-O-(tert-butyldimethylsilyl)-5′-N-(4-monomethoxytritylamino)-3′-O-succinyl-5′-deoxycytidine, a new monomer required for the solid-phase synthesis of cytidyl RNG oligonucleotides.     

Electrochemical characterization of small organic hole-transport molecules based on the triphenylamine unit

A series of substituted triphenylamine-containing organic compounds are synthesized and their hole-transport properties are examined by electrochemical and spectroelectrochemical methods. Several substituted tirphenylamines exhibited irreversible electron-transfer reactions both in the oxidative and reductive scan. On the other hand, the cyclic voltammograms of the p-phenylenediamine series are well defined. N,N^′-bis(4-nitrophenyl)-N,N^′-diphenyl-1,4-phenylenediamine (NPD) exhibited two reversible oxidation redox couples at +1.00 and +1.28 V vs. Ag/AgCl in dichloromethane solution. There is one reversible reduction redox couple at −1.12 V and one irreversible wave with E_p,c at −1.87 V. Cyano-substituted p-phenylenediamine (CPD) exhibited similar oxidation redox couples. Amino-substituted p-phenylenediamine (APD) is easier to oxidize than NPD and CPD. APD exhibits two reversible oxidation redox couples at +0.40 and +0.70 V and two extra irreversible oxidation waves at +1.26 and +1.52 V. Optically transparent thin-layer electrode (OTTLE) coupled with UV/Vis/NIR spectroscopy was used to examine the oxidation products of the above reactions. The electrogenerated cation and dication of the substituted p-phenylenediamine are very stable in the spectroelectrochemical studies. Oxidation of the compound APD exhibited a distinguished absorption pattern, which is different from those of compound NPD and compound CPD.     

Electrochemical and electrochromic properties of novel aromatic poly(amine-amide)s derived from N,N′-bis(4-carboxyphenyl)-N,N′-diphenyl-1,4-phenylenediamine

A series of novel triphenylamine-containing aromatic poly(amine-amide)s were prepared from the dicarboxylic acid, N,N′-bis(4-carboxyphenyl)-N,N′-diphenyl-1,4-phenylenediamine, and various diamines by direct phosphorylation polycondensation. All the poly(amine-amide)s were amorphous, soluble in a variety of organic solvents, and could be solution cast into transparent, tough, and flexible films with good mechanical properties. They had useful levels of thermal stability associated with relatively high glass-transition temperatures (195-280 °C). These polymers exhibited strong UV-Vis absorption bands at 330-346 nm and their photoluminescence showed maximum bands around 516-535 nm in NMP solution. The hole-transporting and electrochromic properties are examined by electrochemical and spectroelectrochemical methods. Cyclic voltammograms of the poly(amine-amide)s prepared by casting polymer solution onto an indium-tin oxide (ITO)-coated glass substrate exhibited two reversible oxidative redox couples at potential 0.73-0.78 V and 1.12-1.18 V, respectively vs Ag/AgCl in acetonitrile solution. All the poly(amine-amide)s exhibited excellent reversibility of electrochromic characteristics by continuous ten cyclic scans between 0.0 and 1.40 V, with a color change from original pale yellowish neutral form to the green and then to blue oxidized forms.     

(N-7-Azaindolyl)oligothiophenes: synthesis, characterization, and photophysical properties

The synthesis of a new series of mono- and oligothiophenes capped by 7-azaindoles such as 2-(N-azaindolyl)thiophene (1), 2-(N-azaindolyl)-5′-(bromo)oligothiophenes (2a-4a), and 2,5′-bis(N-azaindolyl)oligothiophenes (2b-4b) has been investigated. The reaction of 7-azaindole with 2-bromothiophene under the modified Ullmann condensation conditions led to the formation of 1. Simple extension of the same method to the reaction of 2,5′-dibromooligothiophenes in the presence of 4-5 M excess of 7-azaindole led to the formation of 2a-4a and 2b-4b in moderate overall yields (40-55%). All compounds were fully characterized by analytical and various spectroscopic techniques. The structures of 2b, 3b, and 4b were determined by X-ray diffraction analyses. All three compounds show several intermolecular C(π)?H interactions leading to the formation of herringbone packing in the solid-state structure. The UV absorption spectra of 1-4 consist of three characteristic electronic transitions corresponding to n→π^∗ and π→π^∗ transitions arising out of the π-conjugation of the entire molecule as well as local aromatic units. The emission spectra of the same compounds show intense fluorescence bands at the wavelengths between 422 and 495 nm. The length of the thiophene chain and the presence of bromine atom influence the band position of both absorption and emission spectra. While the extension in π-conjugation causes the reduction in the band gap, the bromine atom shifts the electronic transition energy to the blue region. The cyclic voltammetric measurements were performed with 1-4, which show that the compounds exhibit a typical pseudo-reversible redox wave with E_ox in the range 0.6-1.2 V.