Synthesis and photophysical studies of new pyrenylamino acids

Two new pyrenylamino acid derivatives were synthesized from β-bromodehydroalanine derivatives in good yields using addition and elimination reactions.     

Synthesis and anticancer activities of porphyrin induced anticancer drugs

In view of the property of porphyrin's accumulation selectively in tumor,the ftorafur was modified by binding a porphyrin block to improve its tumor targeting and reduce its side effects.These novel porphyrin derivatives and metal compounds were synthesized under mild conditions with satisfactory yield,and the constructions of all these new compounds were characterized by UV,IR,MS, ~1H NMR spectra and elementary analysis.Their anticancer activities were evaluated by MTT assay;the results indicated that the anticancer activities of compounds 4a-c were twice as high as that of ftorafur.     

Synthesis and characterization of a water-soluble porphyrin with a cyclic sulfone

Water-soluble sulfonated tetraarylporphyrins are studied in a wide variety of contexts including as analytical reagents and as possible agents in cancer photodynamic therapy as well as in antiviral and antidiabetic applications. Herein, we report the first synthesis of a pentasulfonated porphyrin bearing an internal cyclic sulfone ring. Treatment of 5,10,15,20-tetrakis(4-sulfonatophenyl)porphyrin (TPPS4) with fuming H₂SO₄ gave a structure consistent with initial sulfonation followed by dehydration to give a sulfone bridge between an ortho-position of one of the phenyl groups and a β-pyrrole position on the porphine ring (TPPS4Sc). The structure was established by electrospray mass spectrometry and ¹H NMR. The Soret UV-visible absorption is red shifted by about 32 nm compared to that of TPPS4.     

Morpholine hydrazone scaffold: Synthesis,anticancer activity and docking studies

In this paper, synthesis and anticancer activities of morpholine hydrazones scaffold(1-17) thoroughly studied. Small series of morpholine hydrazones synthesized by treating 5-morpholinothiophene-2-carbaldehyde with different aryl hydrazides to form morpholine hydrazones scaffold(1-17). The in vitro anticancer potential of all these compounds was checked against human cancer cell lines like Hep G2(human hepatocellular liver carcinoma) and MCF-7(human breast adenocarcinoma). Analogs 13 had similar substantial cytotoxic effects towards Hep G2 with IC_(50) value 6.31±1.03μmmol/L when compared with the standard Doxorubicin(IC_(50)value 6.00±0.80μmmol/L); while compounds 5,8 and 9 showed potent cytotoxicity against MCF-7 with IC_(50) value 7.08±0.42μmmol/L, 1.26±0.34μmmol/L and11.22±0.22μmmol/L respectively when compared with the standard Tamoxifen(IC_(50)= 11.00±0.40μmol/L). Molecular docking studies also performed to understand the binding interaction.     

Synthesis, electrochemical, and photophysical studies of multicomponent systems based on porphyrin and ruthenium(II) polypyridine complexes

Two ruthenium tris-bipyridine functionalized porphyrins 4, 8 and their Zn derivatives 4-Zn, 8-Zn were designed, synthesized, and characterized. The redox potentials of these complexes as well as their corresponding monomeric reference porphyrin and ruthenium bipyridine complexes were also measured for comparison. Primary dynamic studies on the electron injection and backing recombination between these complexes and TiO₂ nanoparticles were carried out by means of transient absorption spectroscopy. The results indicate that a long-lived charge separation state was obtained in these assemblies.     

Synthesis,EGFR-TK inhibition and anticancer activity of new quinoxaline derivatives

Abstract

Ethyl 4-substituted-3-oxo-quinoxaline-2-carboxylates 3–5 were obtained via alkylation of ethyl 3-oxo-3,4-dihydroquinoxaline-2-carboxylate (1). Compound 1 was heterocyclized using hydrazines, ethylenediamine, and ethanolamine to give pyrazoloquinoxalines 6, 7, diazepinoquinoxaline 8, and oxazepinoquinoxaline 10. The quinoxaline-2-carboxamides 9, 11, 12 were prepared via condensation of compound 1 with different amines. Compound 1 was thiated using Lawesson’s reagent affording quinoxaline-3-thione 13, in fair yield. In addition, the reaction of 4-methyl-3-oxoquinoxaline 3 with some binucleophiles led to a series of new oxoquinoxaline derivatives 14–18. The molecular structure of compounds 1, 3, and 9 was confirmed by X-ray crystallography.

The anti-proliferative activity showed that among all the tested compounds, compounds 3, (IC₅₀ 2.51?±?3.0, 4.22?±?1.6 and 2.27?±?1.9?µM), 11 (IC₅₀ 1.32?±?2.61, 1.41?±?1.23 and 1.18?±?1.91?µM) and 17 (IC₅₀ 1.72?±?1.32, 1.85?±?0.94 and 1.92?±?4.83?µM) showed noteworthy anti-proliferative effects against the three cancer cell lines, HCT116, HePG2 and MCF7, respectively, compared to the reference drugs doxorubicin (IC₅₀ 1.41?±?0.58, 0.90?±?0.62 and 1.01?±?3.02?µM) and erlotinib (IC₅₀ 1.63?±?0.81, 1.57?±?0.62 and 1.49?±?0.54?µM). Compounds 3 (0.899?nM), 11 (0.508?nM) and 17 (0.807) showed strong EGFR inhibitory activity compared to Erlotinib (0.439?nM) and these results are in agreement with the docking study. These results suggest that compounds could probably be promising anticancer agents with EGFR inhibitory activity.     

Synthesis and anticancer activity studies of alpha-aminoalkylated conjugated nitroalkenes

Novel alpha-aminoalkylated conjugated nitroalkenes which inhibit human cervical cancer (HeLa) cell proliferation by binding to tubulin were synthesized by imidazole/LiCl-mediated reaction of conjugated nitroalkenes with N-tosylimines.     

Synthesis,characterization, and antileukemic activity of new water-soluble analogs of prodimin

Russian Chemical Bulletin - Two new compounds from the class of bis(3-halopropionyl)amides were synthesized by the reaction of 3-halopropionyl chloride with N,N′-dimethylethylenediamine....     

Synthesis,characterization, and photophysical studies of new bichromophoric ruthenium(II) complexes

The photophysical properties of a series of prepared ruthenium tris(bipyridine) complexes, covalently linked to aromatic species, of type [Ru(bpy)(2)-(4-methyl-4'-(arylaminocarbonyl)-2,2'-bipyridine)](2+) ([Ru(bpy)(2)(mbpy-L)](2+), where bpy = 2,2'-bipyridine; mbpy = 4-methyl-4'-carbonyl-2,2'-bipyridine; and L = 2-aminonaphthyl (naph), 9-aminoanthryl (anth), 1-aminopyrenyl (pyr), or 9-aminoacridinyl (acrd)) were studied by electronic absorption spectroscopy and steady state and time resolved luminescence spectroscopies. The absorption spectra of the MLCT electronic transition of the complexes are similar, which is in agreement with a practically constant redox potential of Ru(III/II) close to 1.28 V versus Ag/AgCl. However, the luminescence spectra of the new complexes are red shifted compared to Ru(bpy)(3)(2+), and this effect is ascribed to solvation and inductive effects of the amide group which enhance the symmetry breakdown among the three bipyridyl ligands. The energy stabilization of the (3)MLCT state is in the range 2.1-8.4 kJ/mol. The triplet-triplet energy transfer between the Ru complex and the aromatic species linked by an amide spacer is a slow process with rate constants of 2.6 x 10(4), 3.6 x 10(4), and 4.9 x 10(4) s(-)(1) for anthracene, acridine, and pyrene as acceptors in methanol, respectively. The energy transfer rate constant increases with decreasing polarity of the solvent. In dichloromethane, the rate constants for anthracene, acridine, and pyrene acceptors are 2.6 x 10(5), 1.5 x 10(5), and 2.9 x 10(5) s(-)(1), respectively. The low efficiency of energy transfer is due to the small difference in triplet energy between donor and acceptor species, weak electronic coupling, and unfavorable Franck-Condon factors, despite the short separation distance between donor and acceptor species in an amide bridge.     

Synthesis and photophysical studies of a new nonaggregated C60-silicon phthalocyanine-C60 triad

A C60-SiPc-C60 triad showing no aggregation is synthesized and characterized. Photoexcitation of the triad results in formation of the charge-separated state by photoinduced electron transfer from the singlet excited state of the SiPc moiety to the C60 moiety. The charge-separated state has a lifetime of 5 ns in benzonitrile at 298 K.     

Synthesis and anticancer activity of some new pyridine derivatives

Different substituents were introduced in positions 2 and 6 of 2,6 diaminopyridine in order to obtain new heterocyclic compounds. A new series of aza pyridine, imidazopyridine, benzodiazepine, indole, pyrimidine, and benzimidazole heterocyclic derivatives were synthesized in good yields. The anticancer activities of some of the new compounds were evaluated against liver cancer cell line HEPG2. Compounds 3, 4, 10, 11, 12, and 17 showed the highest activity when compared to 5-flurouracil (5-FU) and doxorubicin (DOX) chemotherapy.     

Synthesis,modeling, and biological studies of new thiazole-pyrazole analogues as anticancer agents

A series of various substituted thiazole-pyrazole hybrids 5, 7, 8, and 9 were synthesized, and their chemical structures were confirmed by spectral data (infrared, ¹H & ¹³C NMR and Mass). The frontier molecular orbital structural and energetic properties of the targeting thiazole-pyrazole hybrids were explored using the DFT/B3LYP methodology. The data indicated that they had a low energy gap (ΔE_H-L), 1.51–2.42 eV, and may be sorted as 6 < 9 < 7 < 8 < 4 < 3 < 5. The synthesized thiazole-pyrazole hybrids were explored for their activities towards HepG2, MCF-7, and HCT-116 in contrast to doxorubicin. The newly synthesized thiazole-pyrazole analogues demonstrated an acceptable efficiency towards the HepG2 cancer cell line in accordance with this order: 8 > 9 > 7 > 6. Meanwhile, most of the synthesized analogues displayed a significant reduction for the activity of the CAIX inhibitor, with IC₅₀ = 0.071 ± 0.015 to 0.902 ± 0.043 µM. Likewise, they revealed an IC₅₀ = 0.119 ± 0.043 to 0.906 ± 0.04 µM for CAXII inhibitor. Moreover, the newly synthesized thiazole-pyrazole analogues were exposed to the theoretical molecular docking study with PDB:1RHJ as the crystal structure of caspase-3 to examine their antiapoptotic effect as well as their certain properties on the caspase-3 enzyme.     

Synthesis and photophysical studies of siloxane-tethered cyclophanes

Novel siloxane tethered para divinylarene cyclophanes, containing phenyl, biphenyl and naphthalene rings as the aromatic nuclei, were prepared by the hydrolytic condensation of the corresponding bis{[dimethyl(i-propoxy)silyl]vinyl}arenes under basic conditions.The photophysics of the cyclophanes were investigated using UV and fluorescence spectroscopy.     

Synthesis,characterization, and anticancer activity of some metal complexes with a new Schiff base ligand

A new Schiff base ligand, 2-((E)-((4-(((E)-benzylidene)amino)phenyl)imino)methyl)-naphthalene-1-ol, was prepared by the reflux condensation of p-phenylenediamine with 2-hydroxy-1-naphthaldehyde and benzaldehyde. Metal complexes were prepared by reacting the ligand with metal salts: VCl₃, CrCl₃·6H₂O, MnCl₂·3H₂O, FeCl₃·6H₂O, CoCl₃·6H₂O, NiCl₂·6H₂O, CuCl₂·2H₂O, and ZnCl₂. The ligand and its metallic complexes were characterized by various techniques such as elemental analysis, AAS, NMR, IR, UV–Vis, TGA, DTA, XRD and TEM. The data confirmed that the ligand coordinated with the metal ions in a bidentate nature, bonding through its azomethine nitrogen atom and phenolic oxygen atom; this gave an octahedral geometry. The XRD patterns of the complexes indicated that they were of various structures: the Mn(II), Co(III), and Cu(II) complexes were triclinic, the ligand and Ni(II) complex were orthorhombic, the V(III) and Zn(II) complexes were hexagonal, the Cu(II) complex was monoclinic, and the Fe(II) complex was cubic. TEM analysis confirmed that the complexes were nanoscale in nature. The antibacterial and antifungal activities of the ligand and its complexes against Salmonella enterica serovar typhi and Candida albicans were investigated by the hole plate diffusion method. It was observed that the Co(II) and Zn(II) complexes had intermediate antibacterial activities, while the V(III) complex had the highest activity against C. albicans fungi. The in vitro anticancer activities of the ligand and its metal complexes were tested towards PC-3, SKOV3, and HeLa tumour cell lines, where they exhibited higher antitumour activities against these selected human cell lines than clinically used drugs such as cisplatin, estramustine, and etoposide.     

Synthesis,characterization, DNA interaction studies and anticancer activity of platinum–clotrimazole complexes

New trans-platinum complexes of clotrimazole (CTZ) have been prepared and characterized. Their interaction with DNA and activity against tumour cell lines were evaluated. [Pt (CTZ)₂I₂] (1) was synthesized by the reaction of K₂PtCl₄, KI and CTZ, and [Pt(CTZ)₂Cl₂] (2) by direct reaction of K₂PtCl₄ with CTZ. These complexes were characterized by a combination of elemental analysis, molar conductivity, UV–Vis, IR, and NMR spectroscopy in one and two dimensions. DNA–platinum complex interactions were studied by spectroscopic, thermal denaturation and viscosity titration measurements. Covalent interaction studies were also performed. From these results we suggest that complexes 1 and 2 interact with the minor groove of DNA. Both complexes showed growth inhibitory effects on four out of the six tumour cells lines with GI₅₀ (50% growth inhibition) values in the 5–25 μM range, but there was no indication of cytotoxicity over the range of concentrations tested.     

Electronic spectroscopy, photophysical properties, and emission quenching studies of an oxidatively robust perfluorinated platinum porphyrin

The highly electron-deficient, beta-octafluorinated meso-tetrakis(pentafluorophenyl)-porphyrin (H(2)F(28)TPP) was metalated with platinum to afford the oxidatively robust luminophore [PtF(28)TPP], and its X-ray structure shows that the porphyrin core exists in a slightly saddle-shaped conformation. The absorption spectrum of [PtF(28)TPP] in CH(2)Cl(2) displays a near-UV Soret band (B) at 383 nm (epsilon = 2.85 x 10(5) dm(3) mol(-1) cm(-1)) and two visible Q(1,0) and Q(0,0) bands at 501 (epsilon = 1.45 x 10(4) dm(3) mol(-1) cm(-1)) and 533 (epsilon = 1.36 x 10(4) dm(3) mol(-1) cm(-1)) nm, respectively. These absorption bands of [PtF(28)TPP] are blue-shifted from those in [PtF(20)TPP] (390, 504, and 538 nm, respectively) and [PtTPP] (401, 509, and 539 nm, respectively). Excitation of [PtF(28)TPP] (complex concentration = 1.5 x 10(-6) mol dm(-3)) in dichloromethane at the Soret or Q(1,0) or Q(0,0) band gave a phosphorescence with peak maximum at 650 nm (lifetime = 5.8 micros) and a weak shoulder at 712 nm. Both the emission lifetime and quantum yield vary with solvent polarity, and plots of tau versus E(K) and Phi versus E(K) (where E(K) is the empirical solvent polarity parameter based on the hypsochromic shift of the longest wavelength absorption of the [Mo(CO)(4)[(C(5)H(4)N)HC[double bond]NCH(2)C(6)H(5)]] complex with increasing solvent polarity; see: Kamlet, M. J.; Abboud, J. L. M.; Taft, R. W. Prog. Phys. Org. Chem. 1981, 13, pp 485-630) show linear correlation, indicating that the emission is sensitive to the local environment/medium. Electrochemical studies on [PtF(28)TPP] by cyclic voltammetry showed no porphyrin-centered oxidation at potential < or = 1.5 V versus Ag/AgNO(3), demonstrating that [PtF(28)TPP] is more resistant toward oxidation than [PtF(20)TPP] (E(1/2) = 1.33 V) and [PtTPP] (E(1/2) = 0.97 V). The porphyrin-centered reduction of [PtF(28)TPP] occurs at -0.75 and -1.18 V, which is anodically shifted from those at -1.06 and -1.55 V in [PtF(20)TPP], and -1.51 V in [PtTPP], respectively. The excited-state reduction potential of [PtF(28)TPP] is estimated to be 1.49 V versus Ag/AgNO(3). Over 97% of the emission intensity of [PtF(28)TPP] was retained after irradiation with a high power mercury arc lamp (500 W) for 14 h, compared to 90% and 12% for [PtF(20)TPP] and [PtTPP], respectively; hence, [PtF(28)TPP] exhibits superior photostability. Quenching of the emission of [PtF(28)TPP] by oxygen, alcohol, catechol, and butylamine reveals that [PtF(28)TPP] is an oxidatively robust material with medium-sensitive photoluminescence properties.     

Design, synthesis, and photophysical characterization of water-soluble chlorins

The use of chlorins as photosensitizers or fluorophores in a range of biological applications requires facile provisions for imparting high water solubility. Two free base chlorins have been prepared wherein each chlorin bears a geminal dimethyl group in the reduced ring and a water-solubilizing unit at the chlorin 10-position. In one design (FbC1-PO3H2), the water-solubilizing unit is a 1,5-diphosphonopent-3-yl ("swallowtail") unit, which has previously been used to good effect with porphyrins. In the other design (FbC2-PO3H2), the water-solubilizing unit is a 2,6-bis(phosphonomethoxy)phenyl unit. Two complementary routes were developed for preparing FbC2-PO3H2 that entail introduction of the protected phosphonate moieties either in the Eastern-half precursor to the chlorin or by derivatization of an intact chlorin. Water-solubilization is achieved in the last step of each synthesis upon removal of the phosphonate protecting groups. The chlorins FbC1-PO3H2 and FbC2-PO3H2 are highly water-soluble (>10 mM) as shown by 1H NMR spectroscopy (D2O) and UV-vis absorption spectroscopy. The photophysical properties of the water-soluble chlorins in phosphate-buffered saline solution (pH 7.4) at room temperature were investigated using static and time-resolved absorption and fluorescence spectroscopic techniques. Each chlorin exhibits dominant absorption bands in the blue and the red region (lambda = 398, 626 nm), a modest fluorescence yield (Phi f approximately 0.11), a long singlet excited-state lifetime (tau = 7.5 ns), and a high yield of intersystem crossing to give the triplet state (Phi isc = 0.9). The properties of the water-soluble chlorins in aqueous media are comparable to those of hydrophobic chlorins in toluene. The high aqueous solubility combined with the attractive photophysical properties make these compounds suitable for a wide range of biomedical applications.     

Femtosecond to second studies of a water-soluble porphyrin derivative in chemical and biological nanocavities

The interactions of 5,10,15,20-tetrakis(4-sulfonatophenyl)-porphyrin (TSPP) with a quaternary ammonium modified β-cyclodextrin (QA-β-CD) and human serum albumin (HSA) protein in aqueous solutions at pH 7 were studied using steady-state, stopped-flow, and femtosecond to millisecond spectroscopy. TSPP forms 1:1 and 1:2 complexes with QA-β-CD (K(1) = 1.9 × 10(5) M(-1) and K(2) = 7 × 10(3) M(-1)) at 293 K, whereas with the HSA protein only 1:1 complex (K(1) = 1.7 × 10(6) M(-1)) has been found. The chemical and biological nanocavities have notable effects on the fluorescence lifetimes of the Q(x) state (from 9.3 to 11.1 ns in QA-β-CD and 11.6 ns in HSA). Furthermore, the rotational times (400 ps for the free TSPP, 1.6 and 19 ns for QA-β-CD and HSA protein complexes, respectively) clearly indicate the robustness of the formed entities. The confined environment does not affect much the fs dynamics (0.1-0.2 ps) of the encapsulated molecule. However, it clearly affect the ps one (1-2 ps (H(2)O) and 5-10 ps (QA-β-CD and HSA)). The effect of O(2) on the relaxation of the triplet state of the free and encapsulated TSPP is also studied and the obtained results are discussed in light of the shielding effect provided by the chemical and biological cavities. The observed difference, longer triplet lifetime upon encapsulation, might be relevant to the efficiency of this porphyrin in photodynamic therapy. The presteady-state kinetics of the TSPP:HSA has been studied by the stopped-flow spectrometer, and a two-step model was proposed for the complexation processes. The results show the importance of the initial association step for the overall ligand recognition process. This first step occurs with rate constant of ~4 × 10(5) M(-1) s(-1), which is about 5 orders of magnitude larger than the rate constant of the consecutive relaxation processes. We believe that our observations of molecular interaction between TSPP, QA-β-CD, and HSA protein from femtosecond to second at both ground and electronically first excited state give detailed information to improve our understanding of this kind of system and thus for a better design of drug delivery nanocarriers.     

Synthesis and photophysical characterization of porphyrin, chlorin and bacteriochlorin molecules bearing tethers for surface attachment

The ability to tailor synthetic porphyrin, chlorin and bacteriochlorin molecules holds promise for diverse studies in artificial photosynthesis. Toward this goal, the synthesis and photophysical characterization of five tetrapyrrole compounds is described. Each compound bears a surface attachment group. One set contains three meso-substituted porphyrins that differ only in the nature of a surface-binding tether-isophthalic acid, ethynylisophthalic acid or cyanoacrylic acid. The other set includes a porphyrin, chlorin and bacteriochlorin each of which bears an ethynylisophthalic acid tether. The ester derivative of each compound was prepared for solution photophysical characterization studies. The photophysical studies include determination (in toluene or acetonitrile) of the electronic absorption and fluorescence spectra, fluorescence yield and lifetime of the lowest excited singlet state. The excited-state lifetimes range from 1 to 5.6 ns for the five compounds. The radiative rate constant for the excited-state decay was estimated from the photophysical data (fluorescence yield and excited-state lifetime) and from Strickler-Berg analysis of the absorption and fluorescence spectra. The synthesis and characterization of the tetrapyrrole compounds underpin their use as sensitizers in molecular-based solar cells.