An efficient route to VEGF-like peptide porphyrin conjugates via microwave-assisted ‘click-chemistry’

Synthetic cyclopeptides, and particularly those derived from VEGF sequence, present considerable interest for the development of nanodevices devoted to tumour imaging or targeting. In order to provide selective peptide-targeted tetrapyrrolic structures, we designed two meso-porphyrin derivatives anchored to a 17-residue-long cyclopeptide, potent antagonist of VEGF receptors, via a flexible tetraethylene glycol chain. Anchoring was achieved by two different strategies: a classical secondary amide bond formation and microwave-assisted Cu(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition (‘click-chemistry’). These compounds appear to be promising candidates for applications in PDT.     

Synthesis and characterization of new porphyrin/4-quinolone conjugates

New porphyrin/4-quinolone conjugates were synthesized from the Suzuki-Miyaura coupling reaction of a β-borylated porphyrin with bromo-4-quinolones containing N-ethyl and N-d-ribofuranosyl substituents. The use of electrospray ionization tandem mass spectrometry showed important information about the fragmentation pathways of the new compounds. It was possible to distinguish between those compounds with the porphyrin moiety linked at the 6-position of the quinolone unit from their 7-substituted isomers. The new compounds showed to be good singlet oxygen generators.     

Covalently linked heterofullerene-porphyrin conjugates; new model systems for long-lived intramolecular charge separation

Attaching tetraphenyl porphyrins, with peripheral acetyl or malonate groups, to C₅₉N leads to the first covalently linked heterofullerene-porphyrin conjugates that exhibit long-lived intramolecular charge separation.     

两性金属卟啉衍生物的合成

气体传感器的传感介质的研究目前大多集中在具有共轭大。键的外琳和酞青这两类有机化合物上［’·’］．金属叶琳具有载气功能，血红素便是其中一例．这种配合于叶琳环上的金属离子与气体的可逆配位作用，使该化合物在与气体配位前后发生光电性能变化而具有气体传感特性．我们设计将金属叶琳LiLangmuir－Blodgett（L）膜技术组装到具有光波导结构的器件上．为了满足LB膜技术对分子结构的要求，使有机分子在气一液界面能形成较好的单分子层膜，必需对叶琳进行化学修饰，引人长链烷氧基疏水基团和羟基亲水基因．另外，有机分子对气体的选择…     

Synthesis and Biological Evaluation of New Fused Thiazolo[4,5-d] Pyridazine Derivatives

The synthesis of thiazolo[4,5-d]pyridazines and the unknown ring systems, thiazolo[4,5-d]-1,2,4-triazolo- and tetrazolo[4,3-b]pyridazines as well as thiazolo(4,5-d]pyridazino[2,3-c]2H triazines, has been achieved according to different pathways. Biological testing of the new tricyclic heterocycles revealed that some of these compounds possess remarkable antibacterial activity.     

Triazoles as complexing agents: Synthesis and structural studies of some bivalent metal ion complexes with Bi- and tridentate ligands

Summary Co(II), Ni(II), Cu(II), Zn(II) and Cd(II) complexes of 4-amino-5-mercapto-3-trifluoromethyl-s-triazole (AMTT) and 5-mercapto-4-salicylideneamino-3-trifluoromethyl-s-triazole (MSTT) have been synthesized and characterized on the basis of elemental analyses, magnetic measurements, infrared and electronic spectral data. The ligandsAMTT andMSTT were characterized by elemental analyses, infrared and¹H NMR spectral studies.AMTT, involving N and S as donor atoms, andMSTT, involving N, O and S as donor atoms, act as bi- and tridentate ligands, respectively. The geometry of the complexes has been assigned on the basis of magnetic and electronic spectral data. EPR parameters for copper (II) complexes have been calculated. Thermal stabilities of the complexes are also reported. Due to insolubility in water and common organic solvents and infusibility at higher temperatures, all the complexes are thought to be polymeric in nature.

---

Triazole als Komplexierungs-Agentien: Synthese und Strukturuntersuchungen an einigen bivalenten Metallionenkomplexen mit zwei- und dreizähnigen Liganden

Zusammenfassung Es wurden Co(II)-, Ni(II)-, Cu(II)-, Zn(II)- und Cd(II)-Komplexe von 4-Amino-5-mercapto-3-trifluormethyl-s-triazol (AMTT) und 5-Mercapto-4-salizylidenamino-3-trifluormethyl-s-triazol (MSTT) hergestellt und mittels Elementaranalyse, magnetischen Messungen, Infrarot- und Elektronenspektroskopie charakterisiert. Die LigandenAMTT undMSTT wurden elementaranalytisch und spektroskopisch (IR und¹H-NMR) charakterisiert.AMT wirkt über die N-und S-Donoratome als zweizähniger Ligand,MSTT über N, O und S als dreizähniger Ligand. Die Geometrie der Komplexe wurde auf der Basis von magnetischen und elektronenspektroskopischen Daten zugeordnet. Für die Cu(II)-Komplexe wurden die EPR-Parameter berechnet. Die thermischen Stabilitäten der Komplexe wurde ebenfalls untersucht. Wegen ihrer Unlöslichkeit in Wasser und gängigen organischen Lösungsmitteln und der Unschmelzbarkeit bei höheren Temperaturen wird eine polymere Natur der Komplexe angenommen.

     

Synthesis of azidochloromethane and azidobromomethane

By treatment of tris(azidomethyl)amine with dry hydrogen halide, azidochloromethane and azidobromomethane were prepared. The former product, which is more stable than the latter, was isolated as a colorless liquid. The desired azidohalomethanes are intermediates in the nucleophilic substitution of dihalomethanes to generate diazidomethane but could not be detected in this transformation.     

Synthesis and photophysics of porphyrin-fullerene donor-acceptor dyads with conformationally flexible linkers

The synthesis and photophysics of a series of porphyrin-fullerene (P-C₆₀) dyads in which the two chromophores are linked by conformationally flexible polyether chains is reported. Molecular modeling indicates the two moieties adopt a stacked conformation in which the two chromophores are in close proximity. Photoexcitation of the free base dyads in polar solvents such as tetrahydrofuran and benzonitrile, causes electron transfer (ET) to generate charge-separated radical pair (CSRP) states, which were directly detected using transient absorption (TA) techniques. In nonpolar solvents such as toluene, where CSRP states were not directly detected, fullerene triplet state states were formed, according to TA studies as well as singlet oxygen sensitization measurements. The low value of the quantum efficiency for sensitized formation of singlet molecular oxygen [O₂(¹Δ_g)] in toluene and chloroform indicates that singlet energy transduction to give H₂P-¹C₆₀*, followed by intersystem crossing to H₂P-³C₆₀* and energy transfer to ³O₂, is not the operative mechanism. Rather, a mechanism is proposed involving ET to give CSRP states followed by exergonic charge recombination to eventually generate fullerene triplets. Such a mechanism has been demonstrated experimentally for structurally related P-C₆₀ dyads. For the corresponding ZnP-C₆₀ dyads with flexible linkers, only photoinduced ET to generate long-lived CSRP states is observed. Photoinduced charge separation in these dyad systems is extremely rapid, consistent with a through space rather than through-bond mechanism. Charge recombination is up to three orders of magnitude slower, indicating this process occurs in the inverted region of the Marcus curve that relates ET rates to the thermodynamic driving force. These observations once again demonstrate the advantages of incorporating fullerenes as electron acceptor components in photosynthetic model systems.     

Synthesis and Biological Evaluation of New Fused Isoxazolo[4,5‐d] Pyridazine Derivatives

Three new heterocyclic ring systems, isoxazolo[4,5‐d]‐1,2,4‐triazolopyridazines 12‐15 , tetrazolo‐[4,3‐b]pyridazine 18 and isoxazolo[4,5‐d]pyridazino[2,3‐c]2H‐triazines 16 , 17 along with isoxazolo[4,5‐d]pyridazines 2 , 5‐10 have been synthesized. Preliminary screening of these tricyclic heterocycles revealed that some of them possess significant antibacterial and antifungal activity.     

Synthesis of a highly soluble superstructured phenanthroline strapped porphyrin

A highly soluble phenanthroline strapped porphyrin is prepared on multigram scale by appropriate functionalization with C₁₂ chains after the cyclization of the tetrapyrrolic macrocycle.     

Synthesis of boron-dipyrromethene-ferrocene conjugates

Synthesis, spectral, electrochemical and photophysical properties of four BODIPY-ferrocene conjugates in which one or two ferrocenyl groups were covalently connected either directly to boron-dipyrromethene framework or to meso-phenyl group of boron-dipyrromethene unit are described. The BODIPY-ferrocene conjugates were prepared by adopting different synthetic routes. The absorption studies indicated the presence of charge transfer band in BODIPY-ferrocene conjugates in which the ferrocenyl group(s) were directly connected to boron-dipyrromethene framework. The electrochemical studies on conjugates indicated that ferrocenyl group was difficult to oxidize whereas boron-dipyrromethene unit was easier to reduce. The conjugates were non-fluorescent due to electron transfer from ferrocene to boron-dipyrromethene unit. However, when ferrocene was oxidized to ferrocenium ion with an oxidizing agent, the conjugates exhibited fluorescence with decent quantum yields (0.17-0.31) and lifetimes (3.8-5.2 ns).     

Synthesis and photochemical properties of porphyrin-azobenzene triad

Porphyrin-azobenzene triad E-2, having ester spacers between the chromophores, was synthesized and its photochemical and thermal isomerization properties were investigated. Triad E-2 showed little electronic communication among the chromophores according to a comparison of the steady-state absorption and fluorescence spectra of E-2 and their model compounds. E-2 showed photochemical E-Z isomerization and subsequent thermal Z-to-E isomerization. The porphyrin chromophore in Z-2, obtained by photoisomerization, did not strongly affect the transient state of thermal Z-to-E isomerization of the azobenzene unit. The high E-isomer composition at the photostationary state indicates the occurrence of triplet energy transfer between porphyrin and azobenzene. E-2 forms a 1:1 complex with 4,4′-bipyridyl (Bipy). The stability constant for E-2 with Bipy was determined (log K = 4.20 mol⁻¹ dm³) by iterative least-squares fitting to a 1:1 binding model.     

Synthesis of carbohydrate-saccharin conjugates

The synthesis of some carbohydrate-saccharin conjugates has been achieved by treatment of sugar derivatives containing “isolated” hydroxyl groups with equimolar amounts of saccharin, diethyl azodicarboxylate, and triphenylphosphine. Both C-N-linked and C-O-linked compounds can be obtained.     

Synthesis of protein-polymer conjugates

Protein-polymer conjugates are widely employed for applications in medicine, biotechnology and nanotechnology. Covalent attachment of synthetic polymers to proteins improves protein stability, solubility, and biocompatibility. Furthermore, synthetic polymers impart new properties such as self assembly and phase behavior. Polymer attachment at amino acid side-chains and at ligand binding sites is typically exploited. This Emerging Area focuses on synthetic methods to prepare protein-reactive polymers and also employing the protein itself as an initiator for polymerization.     

Synthesis,characterization and antibacterial activity of some new pyrazole based Schiff bases

In the present study a series of new Schiff bases were synthesized. All the synthesized compounds were characterized by IR, ¹H NMR, mass spectral and elemental analyses. Newly synthesized compounds were screened for their antibacterial (Staphylococcus aureus, Bacillus subtilis, Escherichia coli and Pseudomonas aeruginosa) activity. The results revealed that, compounds 3f and 3c have exhibited significant biological activity against the tested microorganisms.     

Synthesis and Biological Activities of 3—（2—Furyl）—4—aryl—1,2,4—triazole—5—thiones

A series of novel compounds 3-(2-furyl)-4-aryl-1,2,4-triazole-5-thiones have been synthesized.All the compounds were characterized by spectral data and elemental analysis. The preliminary biological test showed that some of them exhibited excellent plant-growth regulative activities.     

First Example of a Heptazine-Porphyrin Dyad; Synthesis and Spectroscopic Properties

We have prepared the first example of a porphyrin linked to an heptazine photoactive antenna. The two entities, linked with an alkyl spacer, demonstrate the activity of both active moieties. While they behave electrochemically independantly, on the other hand the spectroscopy shows the existence of energy transfer between both partners.     

Synthesis of triazole-functionalized tetrahydroindazolones by 1,3-dipolar cycloadditions between azides and alkynes

7-Azido-tetrahydroindazolones undergo efficient copper-catalyzed Huisgen 1,3-dipolar cycloaddition reactions with various alkynes leading to a straightforward synthesis of triazole-functionalized tetrahydroindazolones. The latter are interesting molecular platforms in terms of medicinal chemistry.     

Synthesis of 6,8-dichloroquinolones utilizing new method and evaluation of their antibacterial activities

Several 6,8-dichloroquinolone analogues were synthesized from the key intermediate compound of 2,3,4,5-tetrachlorobenzene carbonyl chloride,which was obtained from the starting material of tetrachlorophthalic anhydride.Their in vitro antibacterial activities were evaluated.As a result of this study,compounds 21c and 21d were twofold more potent than ciprofloxacin (CPFX) and norfloxacin (NFLX) against Staphylococcus aureus-9,and with the same potent as CPFX and NFLX while against Escherichia coli-2,but were less potent than references in against Pseudomonas aeruginosa-17.     

Synthesis of 1,2,4-triazolium salts: Reaction of 1-azo-2-azonia-allene salts with nitriles

Summary Alkyl ketone hydrazones1 are oxidized withtert-butylhypochlorite to give geminal chloro azo compounds2. These react with SbCl₅ to give 1-aza-2-azonia-allene salts3 as reactive intermediates which are intercepted with nitriles to yield 3H-1,2,4-triazolium salts5. In most cases these salts rearrange spontaneously to form 1H-triazolium salts6. Hydrolysis of6e–g by NaOH provide bases7a–c, which react with picric acid to give 1H-pyrazolium picrates8.

---

Synthese von 1,2,4-Triazoliumsalzen: Reaktion von 1-Azo-2-azonia-allensalzen mit Nitrilen

Zusammenfassung Alkylketonhydrazone1 werden durchtert-Butylhypochlorit zu geminalen Chlorazoverbindungen2 oxidiert. Diese reagieren mit SbCl₅ zu 1-Aza-2-azonia-allensalzen3, welche mit Nitrilen unter Bildung von 3H-1,2,4-Triazoliumsalzen5 abgefangen werden. In den meisten Fällen lagern diese spontan zu 1H-Triazoliumsalzen6 um. Hydrolyse von6e–g mit NaOH führt zu den Basen7a–c, welche mit Pikrinsäure 1H-Pyrazoliumpikrate8 bilden.