Radioprotective activity of metalladithioacetals derived from N‐substituted naphthylethylimidazoline

A number of organosilicon and organogermanium derivatives of N‐substituted 2‐[1‐(1‐naphthyl)ethyl]‐2‐imidazoline have been reported and the toxicity of these compounds has been determined in mice. In this paper we report the evaluation of the radioprotective activity of new sila‐ and germa‐dithioacetals derived from N‐substituted 2‐[1‐(1‐naphthyl)ethyl]‐2‐imidazoline. Copyright © 2003 John Wiley & Sons, Ltd.     

Synthesis and radioprotective study of new siladithioacetals and germadithioacetals

A series of organosilicon and organogermanium compounds derived from cysteamine, methylcysteamine and 2‐[1‐(1‐naphthyl)ethyl]‐2‐imidazoline have been prepared and their radiopharmacological properties (radioprotective activity and toxicity) have been determined in mice. A number of these new organometallic derivatives have been found to possess radioprotective activity. We have also noted a notable decrease of the toxicity and a fairly large increase in the radioprotective activity in comparison with the unsubstituted organic molecules. Copyright © 2003 John Wiley & Sons, Ltd.     

Synthesis and radioprotective action of silathiazolidines and germathiazolidines

We report on the synthesis and characterization of new sila‐ and germa‐thiazolidines derived from 2‐[1‐(1‐naphthyl)ethyl]‐2‐imidazoline. The radioprotective activity was evaluated in mice by intraperitoneal injection. A notable diminution in the toxicity and increase in radioprotective efficacy were shown for the organometallic derivatives compared with the unsubstituted organic precursors. For some of the cyclic compounds, a delay effect was observed tranducing a slow opening in vivo of the thiazolidine ring. Copyright © 2004 John Wiley & Sons, Ltd.     

Compounds having thiourea moiety as derivatization reagents in liquid chromatography/electrospray ionization–tandem mass spectrometry (LC/ESI‐MS/MS): synthesis of derivatization reagents for carboxylic acids

The derivatization reagents for carboxylic acids, N‐(Pyridin‐3‐yl)hydrazinecarbothioamide, N‐[4‐(dimethylamino)phenyl]hydrazinecarbothioamide, 1‐(2‐aminoethyl)‐3‐(pyridin‐3‐yl)thiourea, 1‐(2‐aminoethyl)‐3‐[4‐(dimethylamino)phenyl]thiourea and 4‐(2‐aminoethyl)‐N‐phenylpiperazine‐1‐carbothioamide were synthesized. These reagents reacted with carboxylic acids at 60°C for 45 min in the presence of the condensation reagents. The generated derivatives were favorably separated on the reversed‐phase column and sensitively detected by electrospray ionization tandem mass spectrometry. These reagents enhanced the electrospray ionization response of the analyte and generated a particular product ion efficiently by collision‐induced dissociation, and thus they were suitable for MS/MS detection. Copyright © 2010 John Wiley & Sons, Ltd.     

Synthesis and radiopharmacological study of new metallated thiazolidines and dithioacetals of N-allyl-substituted cysteamine and methylcysteamine

New germa- and silathiazolidines or germa- and siladithioacetals with N-allyl-substituted cysteamine and methylcysteamine ligands have been synthesized and their pharmacological properties (toxicity, radioprotective activity) have been studied. A notable decrease in the toxicity and a rather large increase in the radioprotective activity of these new organometallic derivatives compared to N-allyl-substituted cysteamine and methylcysteamine were observed.     

Comprehensive Evaluation of the Physicochemical Properties of LnIII Complexes of Aminoethyl‐DO3A as pH‐Responsive T1‐MRI Contrast Agents

N‐Substituted aminoethyl groups were attached to 1,4,7,10‐tetraazacyclododecane‐1,4,7‐triacetic acid (DO3A) with the aim to design pH‐responsive Ln^III complexes based on the pH‐dependent on/off ligation of the amine nitrogen to the metal ion. The following ligands were synthesized: AE ‐ DO3A (aminoethyl‐DO3A), MAE ‐ DO3A (N‐methylaminoethyl‐DO3A), DMAE ‐ DO3A (N,N‐dimethylaminoethyl‐DO3A) and MEM ‐ AE ‐ DO3A (N‐methoxyethyl‐N‐methylaminoethyl‐DO3A). The physicochemical properties of the Ln^III complexes were investigated for the evaluation of their potential applicability as magnetic resonance imaging (MRI) contrast agents. In particular, a ¹H and ¹⁷O NMR relaxometric study was carried out for these Gd^III complexes at two different pH values: at basic pH (pendant amino group coordinated to the metal centre) and at acidic pH (protonated amine, not interacting with the metal ion). Eu^III complexes allow one to estimate the number of inner‐sphere water molecules through luminescence lifetime measurements and obtain some structural information through variable‐temperature (VT) high‐resolution ¹H NMR studies. Equilibria between differently hydrated species were found for most of the complexes at both acidic and basic pH. The thermodynamic stability of Ca^II, Zn^II, Cu^II and Ln^III complexes and kinetics of formation and dissociation reactions of Ln^III complexes of AE ‐ DO3A and DMAE ‐ DO3A were investigated showing stabilities comparable to currently approved Gd^III‐based CAs. In detail, higher total basicity (Σlog K_i^H) and higher stability constants of Ln^III complexes were found for AE ‐ DO3A with respect to DMAE ‐ DO3A (i.e., log K_{Gd‐ AE‐DO3A} =22.40 and log K_{Gd‐ DMAE‐DO3A} =20.56). The transmetallation reactions of Gd^III complexes are very slow (Gd‐ AE ‐ DO3A : t_1/2=2.7×10⁴ h; Gd‐ DMAE ‐ DO3A : 1.1×10⁵ h at pH 7.4 and 298 K) and occur through proton‐assisted dissociation.     

Synthesis of N‐aryl‐2‐amino‐4‐oxo‐3,4‐dihydrothieno[2,3‐d]pyrimidine‐6‐carboxamides

Synthetic routes for the preparation of methyl 2‐amino‐4‐methoxythieno[2,3‐d]pyrimidine‐6‐carboxylate (4) ‐ useful intermediate for lipophilic and classical antifolates from 2‐amino‐4,6‐dichloropyrimidine‐5‐car‐baldehyde (1) have been studied. It has been shown that more efficient synthesis of compound 4 includes the preparation of 4‐methoxy derivative 7 and subsequent tandem substitution/annulation reaction with methyl mercaptoethanoate in dimethylformamide in the presence of potassium carbonate and molecular sieves 4 Å. Compound 4 was used for the synthesis of N‐aryl 2‐amino‐4‐oxo‐3,4‐dihydrothieno[2,3‐d]‐pyrimidine‐6‐carboxamides 10a‐c, including an analog of folic acid with amide bridge ‐ N‐(4‐{[(2‐amino‐4‐oxo‐3,4‐dihydrothieno[2,3‐d]pyrirnidin‐6‐yl)carbonyl]amino}‐benzoyl)‐L‐glutamic acid (10c) .     

Analysis of Nitric Oxide from Chemical Donors Using CMOS Platinum Microelectrodes

Electrochemical detection of NO generated from chemical donors is reported. Because NO is an important biological messenger, many donor sources and detection methods have been developed. Few reports have characterized NO donors using electrochemistry despite electrochemical techniques being sensitive and selective. Here, a CMOS platinum microelectrode array is interfaced with a microfluidic device for the electrochemical analysis of NO from (Z)‐1‐[N‐(2‐aminoethyl)‐N‐(2‐ammonioethyl)amino]diazen‐1‐ium‐1,2‐diolate (DETA/NO). The donor parent amine fouls the electrode, resulting in substantial signal loss, but an electrochemical cleaning method was developed that substantially reduces fouling and allows detection of NO between 90 nM and 1 µM.     

新型含吡啶酰胺基希夫碱多齿配体的合成,光谱,晶体结构及抑菌活性研究

采用稀释法与胺5倍过量合成了一种新型的含吡啶环的开链二胺1a（N，N′-双(2-氨基乙基)－2，6-吡啶二甲酰胺）。此外，合成了六个新型多齿希夫碱配体N，N′－双(β－R－苯甲醛亚胺基乙基)－2，6－吡啶二甲酰胺[其中，R=H(2a)，o-OH(2b)，p-OH(2c)，m-NO₂(2d)，p- N(CH₃)₂(2e)]及N，N′-双[γ-水杨醛亚胺基正丙基]－2，6－吡啶二甲酰胺2f。通过元素分析,紫外－可见光谱，红外光谱，氢核磁共振谱及质谱对化合物进行了表征。通过化合物2e的单晶结构X－射线单晶衍射分析表明该晶体属于立方晶系P－1空间群，其晶胞参数为：a=11.010(2) nm，b=13.865(3) nm，c=9.6537(19) nm，α=102.77(2)º，β=92.07(3)º，γ=87.98(3)º，V=1435.7(5) nm³，Z=2，D_c=1.230 mg•cm^-3，M_r=531.66。微量热法检测了化合物对大肠杆菌的抑制作用，并初步分析了化合物结构与抗菌活性之间的关系。实验结果表明，所有化合物都对大肠杆菌有抑制作用，其中水杨醛希夫碱的抑菌活性最好。     

Synthesis and cytotoxic evaluation of some substituted pyrazole zirconium (IV) complexes and their biological assay

Pyrazole and their derivatives are found to have intense biological efficiency. In the present work some substituted pyrazole derivatives were synthesized and used as ligands (4‐[2‐vinylthiophene]‐3‐methyl pyrozolin‐5(4H) ‐ one (L₁), 4‐[4‐chloro benzylidine]‐3‐methyl pyrozolin‐5(4H) ‐ one (L₂) and 4‐[4‐dimethylnitro benzylidine]‐3‐methylpyrozolin‐5(4H) ‐ one (L₃)) to prepare the zirconium (IV) complexes. The synthesized ligands and their complexes were obtained as colored powdered materials and were characterized using magnetic measurements, melting point, molar conductance, infrared, electronic, ¹HNMR, mass spectra and thermogravimetric analyses. All of the tested compounds showed good microbial activity against pathogenic microorganisms. The tested compounds exhibited considerable antitumor activity and cytotoxic specificity towards human colon carcinoma cell line (HCT‐116).     

Novel pyridinium salts as cationic thermal and photoinitiators and their photosensitization properties

Novel pyridinium salts [N‐(α‐phenylbenzyl)‐, N‐(1‐naphthylmethyl)‐, or N‐cinnamyl p‐ or o‐cyanopyridinium hexafluoroantimonates] were synthesized by the reaction of p‐ or o‐cyanopyridine and the corresponding bromides followed by anion exchange with KSbF₆. These pyridinium salts polymerized epoxy monomers at lower temperatures than previously reported for N‐benzyl‐2‐cyanopyridinium hexafluoroantimonate. The o‐substituted pyridinium salts showed higher activity than the p‐substituted ones, and the crosslinked epoxy polymers cured with these initiators showed higher glass‐transition temperatures. These pyridinium salts photoinitiated radical polymerization as well as cationic polymerization. The photopolymerization was accelerated by the addition of aromatic ketones as photosensitizers. © 2002 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 40: 1037–1046, 2002     

Heterobimetallische Komplexe von Lithium,Aluminium und Gold mit dem N‐[2‐N′,N′‐(Dimethylaminoethyl)‐N‐methyl‐aminoethyl]‐ferrocenyl‐Liganden (η5‐C5H5)Fe{η5‐C5H3[CH(CH3)N(CH3)CH2CH2NMe2]‐2}

Heterobimetallic Complexes of Lithium, Aluminum, and Gold with the N ‐[2‐ N ′, N ′‐(dimethylaminoethyl)‐ N ‐methyl‐aminoethyl]‐ferrocenyl Ligand (η⁵‐C₅H₅)Fe{η⁵‐C₅H₃[CH(CH₃)N(CH₃)CH₂CH₂NMe₂]‐2} N‐[2‐N′,N′‐(dimethylaminoethyl)‐N‐methyl‐aminoethyl]ferrocene FcN,NH ( 1 ) reacts with ⁿBuLi under formation of the lithium organyl (FcN,N)Li ( 2 ). At reactions of 2 with AlBr₃ and AuCl · PPh₃ the heterobimetallic organo derivatives (FcN,N)AlBr₂ ( 3 ), (FcN,N)Au · PPh₃ ( 4 ) are formed. A detailed characterization of 2 – 4 was carried out by single crystal x‐ray analyses as well as by NMR and Mößbauer spectroscopy.     

Four‐, five‐ and six‐coordinated transition metal complexes based on naphthalimide Schiff base ligands: Synthesis,crystal structure and properties

Two bidentate Schiff base ligands (HL¹ = N‐n‐butyl‐4‐[(E)‐2‐(((2‐aminoethyl)imino)methyl)phenol]‐1,8‐naphthalimide; and HL² = N‐n‐butyl‐4‐[(E)‐2‐(((2‐aminoethyl)imino)methyl)‐6‐methoxyphenol]‐1,8‐naphthalimide) with their metal complexes [Cu(L¹)₂] ( 1 ), [Zn(L¹)₂(Py)]₂?H₂O ( 2 ) and [Ni(L²)₂(DMF)₂] ( 3 ) have been synthesized and characterized. Single‐crystal X‐ray structure analysis reveals that complex 1 has a four‐coordinated square geometry, while complex 2 is a five‐coordinated square pyramidal structure and complex 3 is a distorted six‐coordinated octahedral structure. Cyclic voltammograms of 1 indicate an irreversible Cu²⁺/Cu⁺ couple. In vitro antioxidant activity assay demonstrates that the ligands and the two complexes 1 and 3 display high scavenging activity against hydroxyl (HO^?) and superoxide (O₂^??) radicals. Moreover, the fluorescence properties of the ligands and complexes 1 – 3 were studied in the solid state. Metal‐mediated enhancement is observed in 2 , whereas metal‐mediated fluorescence quenching occurs with 1 and 3 .     

Preparation,characterization and biological activities of novel ferrocenyl‐substituted azaheterocycle compounds

α‐Haloacetylferrocene and α‐triazolylacetylferrocene have been prepared from acetylferrocene and they have proved to be useful building blocks for the synthesis of ferrocenyl propenone. Two new types of ferrocenyl vinyl triazole compound, (Z,E)‐ferrocenyl‐[1‐(1,2,4‐triazol‐1‐yl)‐2‐phenyl]‐vinyl‐ones, have been synthesized and their structures characterized by crystal X‐ray diffraction analysis. It has been shown for the first time that ferrocene, as an organometallic compound, has been introduced into bioactive triazole compounds in search of potent bioactive substances. Their biological activities are also discussed. Copyright © 2003 John Wiley & Sons, Ltd.     

Novel Pyrimidine‐based Ferrocenyl substituted Organometallic Compounds: Synthesis,Characterization and Biological Evaluation

Some novel pyrimidine‐based ferrocenyl substituted organometallic compounds were synthesized via multistep reactions, well characterized by different spectroscopic techniques and elemental analyses and evaluated for in vitro antiprotozoal susceptibility against HM1: IMSS strain of Entamoeba histolytica. The results of antiprotozoal susceptibility unveiled these compounds, as new leads in protozoal chemotherapy as most of the organometallics displayed an exceptionally higher antiamoebic activity (IC₅₀ = 0.055 μM ‐ 0.815 μM) than the reference drug metronidazole which gave IC₅₀ (50% inhibitory concentration) value 1.781 μM in our experiments, concluding that newly synthesized organometallic compounds have potential to be employed as effective antiamoebic agents and these organometallics can be very useful for further optimization work on amoebic chemotherapy.     

Synthesis and Antibacterial Activity of Some New 2,5‐Disubstituted‐1,3,4‐oxadiazole Derivatives

Synthesis of some new oxadiazole derivatives starting from 1,2,3-benzo[d]triazole-1-acetic hydrazide (1) is described. The target compounds 2-(N-substituted-aminocarbonylmethylthio)-5-(1,2,3-benzo[d]triazol-1-ylmethyl)- 1,3,4-oxadiazole (4a—4i) and 2-[2-(N-substituted-aminocarbonyl)ethylthio]-5-(1,2,3-benzo[d]triazol-1-ylmethyl)- 1,3,4-oxadiazole (5a—5i) were obtained in good yields via cyclisation of 1 and subjected to antibacterial activity test against pathogenic bacteria. The halogen containing mono- and di-substituted derivatives showed excellent antibacterial activity compared to other analogues.     

Bioconjugation of D‐glucuronic acid sodium salt to well‐defined primary amine‐containing homopolymers and block copolymers

The synthesis of well‐defined carboxylic acid‐functionalized glycopolymers prepared via one‐step postpolymerization modification of poly(N‐[3‐aminopropyl] methacrylamide) (PAPMA), a water‐soluble primary amine methacrylamide, in aqueous medium is demonstrated. PAPMA was first polymerized via aqueous reversible addition‐fragmentation chain transfer polymerization in aqueous buffer using 4‐cyanopentanoic acid dithiobenzoate as the chain transfer agent and 4,4′‐azobis(4‐cyanovaleric acid) (V‐501) as the initiator at 70 °C. The resulting well‐defined PAPMA was then conjugated with D ‐glucuronic acid sodium salt through reductive amination in alkaline medium (pH 8.5) at 45 °C. The successful bioconjugation was proven through proton (¹H) and carbon (¹³C) nuclear magnetic resonance spectroscopy and matrix‐assisted laser desorption/ionization time of flight mass spectrometry analysis, which indicated near quantitative conversion. A similar bioconjugation reaction was conducted with poly(2‐aminoethyl methacrylate) (PAEMA) and poly(2‐aminoethyl methacrylate‐b‐poly(N‐[2‐hydroxypropyl]methacrylamide) (PAEMA‐b‐PHPMA). For the PAEMA homopolymers and block copolymers, however, lower conversion was obtained, most likely because of degradation reactions of PAEMA in alkaline medium. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 3052–3061, 2010     

Synthesis and biological activity of novel N‐tert‐butyl‐N,N′‐substitutedbenzoylhydrazines containing 2‐methyl‐3‐(triphenylgermanyl)propoxycarbonyl

In a search for new insect growth regulators with unusual biological properties and different activity spectrum, we thought that the preservation of the bioactive unit and the introduction of 2‐methyl‐3‐(triphenylgermanyl)propoxycarbonyl in N‐tert‐butyl‐N,N′‐dibenzoylhydrazine would enhance their larvicidal activities to a significant degree. Therefore, we designed and synthesized N′‐tert‐butyl‐N′‐[2‐methyl‐3‐(triphenylgermanyl)propoxycarbonyl]‐N‐benzoylhydrazine and analogs by two procedures. These novel compounds were characterized by elemental analyses, IR, and ¹H NMR. At the same time, N‐tert‐butyl‐N‐substitutedbenzoylhydrazines were prepared by a new method, and some reactions involved were studied. The preliminary results indicate that some compounds have inhibitory effects against plant pathogenetic bacteria such as early blight of tomato. Copyright © 2002 John Wiley & Sons, Ltd.     

Reaction of 2‐[(2‐aminoethyl)amino]ethanol with pyridine‐2‐carbaldehyde and complexation of the products with CuII and CdII along with docking studies

The reaction between 2‐[2‐(aminoethyl)amino]ethanol and pyridine‐2‐carbaldehyde in a 1:2 molar ratio affords a mixture containing 2‐({2‐[(pyridin‐2‐ylmethylidene)amino]ethyl}amino)ethanol (PMAE) and 2‐[2‐(pyridin‐2‐yl)oxazolidin‐3‐yl]‐N‐(pyridin‐2‐ylmethylidene)ethanamine (POPME). Treatment of this mixture with copper(II) chloride or cadmium(II) chloride gave trichlorido[(2‐hydroxyethyl)({2‐[(pyridin‐2‐ylmethylidene)amino]ethyl})azanium]copper(II) monohydrate, [Cu(C₁₀H₁₆N₃O)Cl₃]·H₂O or [Cu(HPMAE)Cl₃]·H₂O, 1 , and dichlorido{2‐[2‐(pyridin‐2‐yl)oxazolidin‐3‐yl]‐N‐(pyridin‐2‐ylmethylidene)ethanamine}cadmium(II), [CdCl₂(C₁₆H₁₈N₄O)] or [CdCl₂(POPME)], 2 , which were characterized by elemental analysis, FT–IR, Raman and ¹H NMR spectroscopy and single‐crystal X‐ray diffraction. PMAE is potentially a tetradentate N₃O‐donor ligand but coordinates to copper here as an N₂ donor. In the structure of 1 , the geometry around the Cu atom is distorted square pyramidal. In 2 , the Cd atom has a distorted octahedral geometry. In addition to the hydrogen bonds, there are π–π stacking interactions between the pyridine rings in the crystal packing of 1 and 2 . The ability of PMAE, POPME and 1 to interact with ten selected biomolecules (BRAF kinase, CatB, DNA gyrase, HDAC7, rHA, RNR, TrxR, TS, Top II and B‐DNA) was investigated by docking studies and compared with doxorubicin.