Itaconic acid hybrids as potential anticancer agents

Molecular Diversity - In this paper, we report the synthesis of novel hybrids 2–14 based on itaconic acid and fluoroaniline, pyridine, indole and quinoline scaffolds. Itaconic acid is a...     

Discovery of ( ±)-3-(1 H -pyrazol-1-yl)-6,7-dihydro-5 H -[1,2,4]triazolo[3,4- b ][1,3,4] thiadiazine derivatives with promising in vitro anticoronavirus and antitumoral activity

A new series of (?±)-(3-(3,5-dimethyl-1H-pyrazol-1-yl)-6-phenyl-6,7-dihydro-5H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazin-7-yl)(phenyl)methanones were efficiently synthesized starting from 4-amino-5-hydrazinyl-4H-1,2,4-triazole-3-thiol 1, acetyl acetone 2, various aromatic and heterocyclic aldehydes 3 and phenacyl bromides 4. All the newly synthesized compounds were tested for their antiviral and antitumoral activity. It was shown that subtle structural variations on the phenyl moiety allowed to tune biological properties toward antiviral or antitumoral activity. Mode-of-action studies revealed that the antitumoral activity was due to inhibition of tubulin polymerization.

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Polyketide Synthase-Mediated O-Methyloxime Formation in the Biosynthesis of the Oximidine Anticancer Agents

Bacterial trans-acyltransferase polyketide synthases (trans-AT PKSs) are modular megaenzymes that employ unusual catalytic domains to assemble diverse bioactive natural products. One such PKS is responsible for the biosynthesis of the oximidine anticancer agents, oxime-substituted benzolactone enamides that inhibit vacuolar H⁺-ATPases. Here, we describe the identification of the oximidine gene cluster in Pseudomonas baetica and the characterization of four novel oximidine variants, including a structurally simpler intermediate that retains potent anticancer activity. Using a combination of in vivo, in vitro and computational approaches, we experimentally elucidate the oximidine biosynthetic pathway and reveal an unprecedented mechanism for O-methyloxime formation. We show that this process involves a specialized monooxygenase and methyltransferase domain and provide insight into their activity, mechanism and specificity. Our findings expand the catalytic capabilities of trans-AT PKSs and identify potential strategies for the production of novel oximidine analogues.     

Regioregularity in Poly(3‐alkoxythiophene)s: Effects on the Faraday Rotation and Polymerization Mechanism

Summary: Poly(3‐alkoxythiophene)s with different degrees of regioregularity were prepared using three different methodologies. It is shown that their Faraday rotation is highly dependent on the degree of regioregularity. The origin of the differences in regiospecificity of the methodologies is discussed.

Structure of the polymer pol 3 .     

Resolution of the A- and B-site hyperfine fields of the spinel system Mg1+t Fe2(1−t ) Ti t O4 in the spin-glass-like state

Spectra for three members of the spinel system Mg_1+t Fe_2(1−t)Ti _t O₄, witht=0.5, 0.6 and 0.7, all showing re-entrant spin-glass-like behavior, were collected at temperatures down to 1.6 K and decomposed in A- and B-site components, both having a broad distribution of hyperfine fields. The numerical results suggest a more pronounced spin canting on A sites as compared to B sites. From spectra recorded at 4.2 K in an applied field of 6 T, and analysed with a sum of two bi-dimensional distributions of hyperfine fields and canting angles, the existence of reversed A-site spins is evidenced. The number of such spins increases with increasing magnetic dilution. Senior Research Associate at the National Fund for Scientific Research, Belgium     

Lambda-type regioregular oligothiophenes: synthesis and second-order NLO properties

The synthesis of a new series of Lambda-type, D-Pi-A regioregular oligothiophenes is described. The simultaneous presence of the chiral centers and the Lambda-type structure disfavored the formation of centro-symmetrical dimeric assemblies. Hence, enhanced first hyperpolarizabilities betaHRS were measured in comparison with those of the corresponding monomers.     

Unusual frequency dispersion effects of the nonlinear optical response in highly conjugated (polypyridyl)metal-(porphinato)zinc(II) chromophores

The syntheses and electrooptic properties of a new family of nonlinear optical chromophores are reported. These species feature an ethyne-elaborated, highly polarizable porphyrinic component and metal polypyridyl complexes that serve as integral donor and acceptor elements. Examples of this structural motif include ruthenium(II) [5-(4'-ethynyl-(2,2';6',2' '-terpyridinyl))-10,20-bis(2',6'-bis(3,3-dimethyl-1-butyloxy)phenyl)porphinato]zinc(II)-(2,2';6',2' '-terpyridine)(2+) bis-hexafluorophosphate (Ru-PZn); osmium(II) [5-(4'-ethynyl-(2,2';6',2'-terpyridinyl))-10,20-bis(2',6'-bis(3,3-dimethyl-1-butyloxy)phenyl)porphinato]zinc(II)-(2,2';6',2'-terpyridine)(2+) bis-hexafluorophosphate (Os-PZn); ruthenium(II) [5-(4'-ethynyl-(2,2';6',2'-terpyridinyl))-15-(4'-nitrophenyl)ethynyl-10,20-bis(2',6'-bis(3,3-dimethyl-1-butyloxy)phen-yl)porphinato]zinc(II)-(2,2';6',2' '-terpyridine)(2+) bis-hexafluorophosphate (Ru-PZn-A); osmium(II) [5-(4'-ethynyl-(2,2';6',2' '-terpyridinyl))-15-(4'-nitrophenyl)ethynyl-10,20-bis(2',6'-bis(3,3-dimethyl-1-butyloxy)phenyl)porphinato]zinc(II)-(2,2';6',2' '-terpyridine)(2+) bis-hexafluorophosphate (Os-PZn-A); and ruthenium(II) [5-(4'-ethynyl-(2,2';6',2' '-terpyridinyl))osmium(II)-15-(4'-ethynyl-(2,2';6',2'-terpyridinyl))-10,20-bis (2',6'-bis(3,3-dimethyl-1-butyloxy)phenyl)porphinato]zinc(II)-bis(2,2';6',2'-terpyridine)(4+) tetrakis-hexafluorophosphate (Ru-PZn-Os). The frequency dependence of the dynamic hyperpolarizability of these compounds was determined from hyperRayleigh light scattering (HRS) measurements carried out at fundamental incident irradiation wavelengths (lambda(inc)) of 800, 1064, and 1300 nm. These data show that (i) coupled oscillator photophysics and metal-mediated cross-coupling can be exploited to elaborate high beta(0) supermolecules that exhibit significant excited-state electronic communication between their respective pigment building blocks; (ii) high-stability metal polypyridyl compounds constitute an attractive alternative to electron releasing dialkyl- and diarylamino groups, the most commonly used donor moieties in a wide range of established nonlinear optical dyes; (iii) this design strategy enables ready elaboration of chromophores having extraordinarily large dynamic hyperpolarizabilities (beta(lambda) values) at telecommunication relevant wavelengths; and (iv) porphyrin B- and Q-state-derived static hyperpolarizabilities (beta(0) values) can be designed to have the same or opposite sign in these species, thus providing a new means to regulate the magnitude of lambda(inc)-specific dynamic hyperpolarizabilities.     

Electronic modulation of hyperpolarizable (porphinato)zinc(II) chromophores featuring ethynylphenyl-, ethynylthiophenyl-, ethynylthiazolyl-, and ethynylbenzothiazolyl-based electron-donating and -accepting moieties

A series of conjugated (porphinato)zinc(II)-based chromophores structurally related to [5-(4-dimethylaminophenylethynyl)-15-(5-nitrothienyl-2-ethynyl)-10,20-bis(3,5-bis(3,3-dimethyl-1-butyloxy)phenyl)]zinc(II) were synthesized using metal-catalyzed cross-coupling reactions involving [5-bromo-15-triisopropylsilylethynyl-10,20-diarylporphinato]zinc(II), [5-bromo-15-(4-dimethylaminophenylethynyl)-10,20-diarylporphinato]zinc(II), [5-(4-dimethylaminophenylethynyl)-15-ethynyl-10,20-diarylporphinato]zinc(II), and [5-(4-nitrophenylethynyl)-15-ethynyl-10,20-diarylporphinato]zinc(II), along with appropriately functionalized aryl, thienyl (or thiophenyl), thiazolyl, benzothiazolyl, and carbazolyl precursors. The linear and nonlinear optical properties of these asymmetrically 5,15-substitued-(10,20-diarylporphinato)zinc(II) chromophores that bear either 2-(9H-carbazol-9-yl)-thiophen-5-yl-ethynyl, 4-dimethylaminophenylethynyl, or 2-(N,N-diphenylamino)thiophen-5-yl-ethynyl electron-releasing groups and an electron-withdrawing group selected from 2-formyl-thiophen-5-yl-ethynyl, 2-(2,2-dicyanovinyl)-thiophen-5-yl-ethynyl, 4-nitrophenylethynyl, 6-nitrobenzothiazol-2-yl-ethynyl, or 5-nitrothiazol-2-yl-ethynyl are reported. The dynamic hyperpolarizabilities of these compounds were determined from hyper-Rayleigh light scattering measurements carried out at a fundamental incident irradiation wavelength (lambda(inc)) of 1300 nm; these measured beta1300 values ranged from 690 --> 1400 x 10(-30) esu. These data (i) show that these neutral dipolar molecules express substantial beta1300 values, (ii) highlight that reductions in the magnitude of the aromatic stabilization energy of (porphinato)metal-pendant arylethynyl groups have a significant impact upon the magnitude of the molecular hyperpolarizability, and (iii) provide insights into advantageous design modifications for closely related structures having potential utility in long-wavelength electrooptic applications.     

Two-step synthesis of high aspect ratio gold nanorods

We describe a very simple, two-step synthetic method to prepare gold nanorods with extremely high aspect ratios (> 20) and average lengths of more than 1000 nm. The method is based on a seed-mediated growth in presence of the surfactant cetyltrimethylammonium bromide. The length and aspect ratios of the nanorods can be manipulated by varying the surfactant concentration.