Asymmetric Mono Research Articles

Tert-Butyl substituted aza-BODIPY-based bromides for phototherapy

Asymmetric mono - and dibromides aza-BODIPYs at 6-site were prepared. The singlet oxygen yield of monobromide MBr-azaBDP with the direct attachment of the –Br group at 6-site was higher than that of vinyl dibromide DBr-azaBDP. Self-assembled MBr-azaBDP-NPs with laser irradiation possessed a photothermal conversion capability. Monobromide MBr-azaBDP was discovered to be an effective PDT-PTT combined therapeutic agent and prospective candidate for tumor phototherapy by integrating tert-butyl free rotation and halogen substitution. However, comparing to MBr-azaBDP, DBr-azaBDP as a fluorescent dye possesses narrower full width at half maxima, higher molar extinction coefficient and fluorescence quantum yield.

Chemoselective Staudinger Reactivity of Bis(azido)phosphines Supported with a π-Donating Imidazolin-2-iminato Ligand.

Synthesis and characterization of new P(III) and P(V) bis(azido)phosphines/phosphoranes supported by an N,N'-bis(2,6-diisopropylphenyl) imidazolin-2-iminato (IPrN) ligand and their reactivity with various secondary and tertiary phosphines result in the formation of chiral and/or asymmetric mono(phosphinimino)azidophosphines via the Staudinger reaction. The reaction of IPrNP(N3)2 (2) or IPrNP(S)(N3)2 (4S) with an excess of tertiary phosphine resulted in the chemoselective formation of IPrNP(N3)(NPMe3) (7) or IPrNP(S)N3(NPR3) (5R), respectively. The chemoselective Staudinger reactivity was also observed in reactions using a secondary phosphine (HPCy2) to produce IPrNP(S)N3[NP(H)Cy2] (6a), which exists in equilibrium with a tautomeric IPrNP(S)N3[N(H)PCy2] form (6b), as confirmed by 31P-31P nuclear Overhauser effect spectroscopy (NOESY). Density functional theory (DFT) calculations point to a combination of energetically unfavorable lowest unoccupied molecular orbitals (LUMOs) and the accumulation of increasing negative charge at the terminal azido-nitrogen upon a single azide-to-phosphinimine conversion that gave rise to the observed chemoselectivity.

Oxidations of 4H‐1,2,6‐Thiadiazines

AbstractThe oxidation of various non‐S‐oxidized 4H‐1,2,6‐thiadiazines with N2O4, meta‐chloroperbenzoic acid (m‐CPBA), Oxone, [bis(trifluoroacetoxy)iodo]benzene (PIFA) and phenyliodine (III) diacetate (PIDA) is reported. Six 3,5‐diamino‐4H‐1,2,6‐thiadiazin‐4‐ones were oxidized to the corresponding sulfones (67–95 % yields) most efficiently using PIFA (3 equiv.). A 3,5‐diphenylthio analogue, however, oxidized at the exocyclic sulfur to give the asymmetric mono sulfoxide using PIFA (3 equiv.) in 86 % yield. 4H‐1,2,6‐Thiadiazine 4‐ylidenemalononitriles, 4‐ylidinemalonates and 4‐phenylimines were oxidized stepwise, initially to sulfoxides using all the above reagents in 31–97 % yields and then to sulfones using N2O4, m‐CPBA or Oxone in 31–89 % yields. Oxidation of a 4‐thione derivative using Oxone (1.5 equiv.) gave the sulfine in 56 %. Unexpectedly, oxidation of 3,5‐diphenyl‐4‐(phenylimino)‐4H‐1,2,6‐thiadiazine 1‐oxide with excess m‐CPBA gave a fused oxaziridine in 98 % yield, while 3,5‐dimorpholino‐4H‐1,2,6‐thiadiazin‐4‐one 1,1‐dioxide in EtOH/MeCN gave a hemiacetal in 56 % yield. Single crystal structures of 3,5‐bis(phenylamino)‐4H‐1,2,6‐thiadiazin‐4‐one 1,1‐dioxide, 4‐ethoxy‐4‐hydroxy‐3,5‐dimorpholino‐4H‐1,2,6‐thiadiazine 1,1‐dioxide, 2‐(1‐oxido‐3,5‐diphenyl‐4H‐1,2,6‐thiadiazin‐4‐ylidene)malononitrile, 2‐[1,1‐dioxido‐3,5‐di(thien‐2‐yl)‐4H‐1,2,6‐thiadiazin‐4‐ylidene]malononitrile and (E)‐4,6‐diphenyl‐5‐(phenylimino)‐7‐oxa‐2‐thia‐1,3‐diazabicyclo[4.1.0]‐hept‐3‐ene 2,2‐dioxide are reported.

Chiral 1,2,3‐Triazolium Salt Catalyzed Asymmetric Mono‐ and Dialkylation of 2,5‐Diketopiperazines with the Construction of Tetrasubstituted Carbon Centers

AbstractNovel asymmetric mono‐ and dialkylation reactions of α‐substituted 2,5‐diketopiperazines catalyzed by new chiral spirocyclic‐amide‐derived triazolium organocatalysts have been developed, resulting in a range of enantioenriched 2,5‐diketopiperazine derivatives containing one or two tetrasubstituted carbon stereocenters. The reactions feature high yields (up to 98%), and excellent cis‐diastereo‐ and enantioselectivities (up to >20:1 dr, >99 % ee), and they provide a new asymmetric synthetic approach to important functionalized 2,5‐diketopiperazine skeletons. Furthermore, a possible reaction mechanism was proposed based on both control experiments and extensive DFT calculations.

Chiral 1,2,3-Triazolium Salt Catalyzed Asymmetric Mono- and Dialkylation of 2,5-Diketopiperazines with the Construction of Tetrasubstituted Carbon Centers.

Novel asymmetric mono- and dialkylation reactions of α-substituted 2,5-diketopiperazines catalyzed by new chiral spirocyclic-amide-derived triazolium organocatalysts have been developed, resulting in a range of enantioenriched 2,5-diketopiperazine derivatives containing one or two tetrasubstituted carbon stereocenters. The reactions feature high yields (up to 98%), and excellent cis-diastereo- and enantioselectivities (up to >20:1 dr, >99 % ee), and they provide a new asymmetric synthetic approach to important functionalized 2,5-diketopiperazine skeletons. Furthermore, a possible reaction mechanism was proposed based on both control experiments and extensive DFT calculations.

Asymmetric mono(imine)pyrrole nickel PMMA catalysts: synthesis, crystal structure, and DFT calculation

Asymmetric mono(imine)pyrrole nickel PMMA catalysts: synthesis, crystal structure, and DFT calculation

Treatment of Reactive Arthritis: A Case Report

Reactive arthritis is clinically defined as inflammatory aseptic arthritis which develops shortly after an extra-articular infection. The classic triad of conjunctivitis, urethritis, and arthritisis found in a minority of patients. Patiepresent with an asymmetric mono- or oligoarthritis that predominantly affect lower limbs. Here, we present a case of reactive arthritis with inadequate primary response to Nonsteroidants Usually l Anti-inflammatory Drugs (NSAIDs).

Cyanine Dyes Containing Quinoline Moieties: History, Synthesis, Optical Properties, and Applications.

Cyanine dyes carrying quinoline moieties are an important class of organic molecules that are of great interest for applications in many fields like medicine, pharmacology, and engineering. Despite their exceptional properties, such as stability, high molar extinction coefficients, and high pH-sensitivity, this class of dyes has been less analyzed and reviewed in the last few decades. Therefore, this review article focuses on discussing the history of quinoline compounds, various synthetic routes to prepare quinolinium salts and symmetrical and asymmetrical mono-, di-, tri-, penta- and heptamethine cyanine dyes, containing quinoline moieties, together with their optical properties and applications as photosensitizers in photodynamic therapy, probes in biomolecules for labeling of nucleic acids, as well as imaging agents.

Electrosynthesis of Mono- and Disulfides Based on C5–C8 Cycloalkanes, Hydrogen Sulfide, and Isomeric Dibutyl Disulfides

A method of synthesis of organic mono-, di-, and polysulfides based on electrochemical reactions of unsubstituted and alkyl–substituted cycloalkanes C5–C8 with di(n-butyl)disulfide (di(tert-butyl)disulfide) and hydrogen sulfide is developed. Three–component electrosynthesis is carried out in methylene chloride under atmospheric pressure, at the room temperature under the conditions of anodic H2S activation to a cation radical fragmented to a proton and a thiyl radical. The suggested approach with application of oxidative conversion initiation allows obtaining asymmetric mono-, disulfides and symmetric disulfides. The yield of biologically active organic sulfur derivatives depends on the electrosynthesis duration, structure of isomeric dibutyl sulfides, alicycle size and saturation degree.

The value of contrast-enhanced musculoskeletal ultrasound for early diagnosis, monitoring of disease activity and assessment of treatment efficacy in patients with rheumatoid arthritis and psoriatic arthritis

Rheumatoid arthritis (RA) and Psoriatic arthritis (PsA) are the most common autoimmune inflammatory joint diseases. The prevalence of RA is at 0,5-1%. The main clinical manifestation of RA is symmetric progressive erosive polyarthtitis. PsA is inflammatory arthritis associated with skin psoriasis. The prevalence of PsA in general population vary from 0,3% to 1%. The disease has heterogeneous clinical features – joint involvement, tenosynovitis, enthesitis, dactylitis, nail changes, eyes disorders, skin lesions. Most patients, at 70-80% of cases, present with asymmetric mono- or oligoarthritis. Both RA and PsA are chronic inflammatory joint disorders which may cause severe structural joint changes and functional deficiency of patients. They have a significant medical and social importance. Within the past two decades musculoskeletal ultrasound (MUS) has become an essential diagnostic method for evaluation of musculoskeletal diseases with ultrasound imaging. MUS is accessible, non-invasive technique which can provide precise information about pathological changes occurring in all articular and periarticular structures in patients with RA and PsA. Advances in technology together with the usage of higher frequency transducers, the possibilities of color/ power Doppler imaging, the implementation of ultrasound contrast agent, have contributed to the progressive development of the methodology. The purpose of this review is to perform the value of contrast-enhanced musculoskeletal ultrasound (CEUS) for early diagnosis, monitoring of disease activity and assessment of treatment efficacy in patients with rheumatoid arthritis and psoriatic arthritis.

Photogeneration of Singlet Oxygen by Tetra(p-Hydroxyphenyl)porphyrins Modified with Oligo- and Polyalkylene Oxides

Mono- and diethylene oxide derivatives of tetra(p-hydroxyphenyl)porphyrin (THPP) with different conformation states are synthesized. These compounds exhibit high photosensitization activity in the generation of singlet oxygen in organic and aqueous (in the solubilized state) phases. It is shown that introducing ethylene oxide moieties into the hydroxyphenyl substituents of THPP increases its solubility in chloroform. In addition, the activity of singlet oxygen 1Δg generation in the reaction of anthracene photooxidation by THPP tetra derivatives in chloroform, where the ethylene oxide fragments are introduced into two phenyl rings and hexadecyl fragments are introduced into another two, is higher than the activity of mono- and di-modified THPP molecules with enthylene oxide molecules at one hydroxyphenyl cycle. The activity of tetra-substituted porphyrin in chloroform, however, is comparable to that of nonsubstituted tetraphenylporphyrin, considered to be one of the most active photosensitizers. The produced ethylene oxide derivatives of THPP are solubilized with pluronic F-127 (triblock copolymer of ethylene- and propylene-oxides)—one of the least toxic and effective polymeric detergents—forming water-soluble forms of the respective porphyrins. It is established that the pluronic solubilization capability (the lowest molar concentration of pluronic required for the complete transfer of porphyrin of a particular molar concentration dissolved in organic phase to the water-soluble form) is higher for asymmetrical mono- and di-derivatives of the THPP than for symmetric tetra-substituted THPP. It is shown that the activity of the solubilized water-soluble form of mono- and tetra-derivatives in tryptophan photoxidation is higher than that of unsubstituted THPP and is comparable to the activity of tetraphenylporphyrin.

ChemInform Abstract: Prolinamide‐Derived Ionic‐Liquid‐Supported Organocatalyst for Asymmetric Mono‐ and Bis‐Aldol Reactions in the Presence of Water.

AbstractA novel recyclable prolinamide‐derived ionic‐liquid‐supported organocatalyst of asymmetric cross‐aldol reactions in aqueous medium is developed.

Pressure-preferred symmetric reactions of 4,4′-bipyridine hydrobromide

High pressure and temperature trigger symmetric chemical reactions of 4,4′-bipyridine hydrobromide monohydrate (44′biPyHBr·H2O) in methanol solution. Above 0.1 GPa and 423 K, the 4,4′-bipyridinium dibromide salt (44′biPy2HBr) precipitates, while the 4,4′-bipyridine free base remains dissolved in the methanol–water mixture. At 0.35 GPa and 473 K, both pyridine moieties are N-methylated and N,N-dimethylbipyridinium dibromide (44′biPy2CH3Br) is formed. None of the high-pressure compounds of 44′biPy2HBr and 44′bPy2CH3Br are solvated, which contrasts with the strong preference of analogous 1,4-diazabicyclo[2.2.2]octane (dabco) monosalts and disalts to form solvates at high-pressure. The high-pressure reactivity of 44′biPyHBr is analogous to that of 1,4-diazabicyclo[2.2.2]octane hydrobromide (dabcoHBr); however, dabcoHBr is asymmetrically N-methylated at one amine site only. This asymmetric mono N-methylation of dabcoHBr has been associated with strong electrostatic interactions between the transannular N-atoms.

Asymmetric mono- and dinuclear GaIII and ZnII complexes as models for purple acid phosphatases

Derivatives of the known dinucleating ligands HL1 (2,6-bis{[bis(pyridin-2-ylmethyl)amino]methyl}-4-methylphenol) and H2L2 (2-{[bis(pyridin-2-ylmethyl)amino]methyl}-6-{[(2-hydroxybenzyl)(pyridine-2-ylmethyl)amino]methyl}-4-methylphenol) with two pivaloylamido hydrogen bond donor substituents, H3L3 and H3L5, have been prepared. The mono-, homo- and heterodinuclear ZnII and GaIII complexes of these ligands have been prepared and characterized. The solution equilibria are discussed on the basis of extensive NMR spectroscopic, mass spectrometric and pH-dependent UV–vis spectroscopic titrations. The phosphoester hydrolysis activity of the complexes has been studied as a function of pH and substrate concentration and analyzed using Michaelis–Menten kinetics. It emerges that the mixed metal (mixed valent) complex of the ligand with an asymmetric disposition of the hydrogen bonding substituents (H3L3) is a functional model for the mixed valent, dinuclear metallohydrolase purple acid phosphatase. This complex combines the essential structural features of the active site of PAP and is the first heterodinuclear model complex mimicking the essential function of PAPs, i.e. the hydrolysis of phosphomonoesters.

Prolinamide‐Derived Ionic‐Liquid‐Supported Organocatalyst for Asymmetric Mono‐ and Bis‐Aldol Reactions in the Presence of Water

AbstractA novel recyclable prolinamide‐derived ionic‐liquid‐supported organocatalyst of asymmetric cross‐aldol reactions in aqueous medium has been developed. In its presence, aromatic aldehydes react with cyclic or linear ketones to afford chiral aldol adducts in moderate to high yields and with excellent dr (anti/syn up to 96:4) and ee (81–99 %) values that do not tend to decline over ten recycles of the catalyst. Furthermore, it allows a highly enantioselective catalytic synthesis of linear bis‐aldols in aqueous medium.

Genetic and Pharmacological Inhibition of Dimethylarginine Dimethylaminohydrolase 1 Is Protective in Endotoxic Shock

The overproduction of vascular NO contributes toward the circulatory collapse observed in patients with septic shock. Dimethylarginine dimethylaminohydrolase (DDAH), which has 2 isoforms, metabolizes asymmetrically methylated arginines (asymmetric mono- or di-methylarginine), endogenously produced NO synthase inhibitors. We wished to investigate whether reducing DDAH1 activity, using genetic and pharmacological approaches, is protective during lipopolysaccharide-induced endotoxic shock. Experiments were conducted in DDAH1 heterozygous knockout mice (DDAH1(+/-)) or naive rats treated with a synthetic pharmacological DDAH inhibitor (L-257). We demonstrate for the first time that L-257 is DDAH1 selective using recombinant human DDAH proteins. DDAH1 mRNA was expressed in aortic but not macrophage cDNA, and consistent with this expression profile, L-257 selectively inhibited NO production from lipopolysaccharide-treated aorta but not macrophages, in culture. Conscious and anesthetized cardiovascular hemodynamics were monitored using implanted radiotelemetry devices or invasive catheters, respectively. Lipopolysaccharide was administered intravenously to model endotoxemia, and all animals presented with circulatory shock. DDAH1(+/-) mice or L-257-treated rats displayed attenuation in the rate of developed hypotension compared with wild-type littermates or vehicle control animals, respectively. Pharmacological and genetic reduction of DDAH1 activity is protective against the vascular changes observed during endotoxic shock.

Asymmetric Mono- and Bis-Squarylium Dyes as Pre-Column and On-Column Labels for Protein Analysis by Capillary Electrophoresis with Laser-Induced Fluorescence Detection

Labeling proteins with fluorescent dyes offers a powerful tool for monitoring protein interactions in vitro and in vivo. In order for this tool to be effective, the nature of the dyes - absorbance and emission properties, solution stability, pH range, and mechanisms for protein interaction - must first be considered. Two new asymmetric, squarylium dyes, bis-SQHN-4d and SQHN-3c, were shown to be only weakly fluorescent in aqueous buffers in the absence of proteins. However, their spectra showed a dramatic increase in fluorescence intensity upon the addition of Human Serum Albumin (HSA) or Bovine Serum Albumin (BSA) as model proteins. The enhanced fluorescence properties, attributed to noncovalent binding, allowed the use of the new squarylium dyes as probes for the low-level detection of proteins in a mixture (including myoglobin (pI=7.16), transferrin (pI=5.9), and HSA (pI=4.8)), separated by Capillary Electrophoresis with Laser-Induced Fluorescence detection (CE-LIF). Because of the low background fluorescence of these probes, on-column labeling was feasible and led to simple and rapid protein detection. This labeling protocol offered greater sensitivity than the more conventional pre-column labeling protocol (with a 10-fold lower limit of detection for HSA with bis-SQHN-4d). A limit of detection for HSA (by CE-LIF with on-column labeling with bis-SQHN-4d) of 3.42 x 10-8 M indicates that this dye is well suited to the development of other protein assays.

Synthesis, antiproliferative activities and telomerase inhibition evaluation of novel asymmetrical 1,2-disubstituted amidoanthraquinone derivatives

A series of diversely asymmetrical mono- or disubstituted 1,2-diamidoanthraquinone derivatives were synthesized and evaluated for drug-induced cytotoxicity by SRB assay, telomerase inhibitory activity by TRAP assay, and hTERT expression by SEAP assay. Interestingly, compounds 4, 11, 21, 32 and 36 exhibited selective potent antiproliferative activities by NCI with IC 50 values in the micromolar range. Of these, only compound 8 showed an IC 50 value of 0.95 μM against PC-3 cell lines (human prostate cancer) by SRB assay. All the synthesized compounds exhibited a poor or modest telomerase inhibitory activity by TRAP assay suggesting another mode of action for these compounds. Compound 11 showed broad inhibition against different types of cancer cell lines in the micromolar and submicromolar range.

Electrochromic Properties of Asymmetric 4,4′-Bipyridinium Nanocomposites with Inorganic Nanoparticles

Asymmetric mono cationic 4,4'-bipyridiniums, 1-butyl-4,4'-bipyridinium bromide (BUBP) and 1-methyl-4,4'-bipyridinium iodide (MEBP) showed electrochromic properties from blue to transparent yellow. The electrochromic bipyridiniums, BUBP and MEBP, were introduced to solid state electrochromic cells by using a solution of the bipyridinium, TiO2, and polymer electrolyte composite. The 4,4'-bipyridinium derivatives was attached to TiO2 nanoparticles and decreased aggregation of TiO2 to afford EC dye-TiO2 nanoparticles with average diameter smaller than 20 nm, as determined by FE-SEM. An all solid state electrochromic cells prepared from the dye-TiO2 nanoparticles showed improved electrochromic response compared to that without TiO2. Thus the cell from the BUBP- TiO2 nanoparticles responded to a step potential of +/-2 V within 7 sec with coloration efficiency of 117. The redox cyclability of the bipyridinium-TiO2 nanoparticles cell was longer than that of the TiO2 free cells. The enhanced properties were attributed to the conductivity and the large surface area of TiO2 nanoparticles.

Cobalt(II) and nickel(II) complexes bearing mono(imino)pyridyl and bis(imino)pyridyl ligands: preparation, structure and ethylene polymerization/oligomerization behaviors

AbstractBACKGROUND: Ethylene oligomerization is the major industrial process to produce linear α‐olefins. Recently much work has been devoted to late transition metal catalysts used in this process, especially those with 2,6‐bis(imino)pyridyl dihalide ligands. Considering that most work has focused on simple modification to the substituents in imino‐aryl rings based on the symmetric bis(imino)pyridyl framework, here we expand this work to the asymmetric mono(imino)pyridyl ligands.RESULTS: The preparation, structure and ethylene polymerization/oligomerization behavior of series of mono(imino) pyridyl–MCl2 and bis(imino)pyridyl–MXn complexes are presented. The systematic studies were focused on the relationship between the catalytic behavior of these complexes for ethylene polymerization/oligomerization and reaction conditions, ligand structures, metal centers and counter‐anions. The influence of the coordination environment on catalyst behavior is also discussed.CONCLUSION: For mono(imino)pyridyl–Co(II) and Ni(II) catalysts bearing the Cl− counter‐anion, good activities ranging from 0.513 × 105 to 1.58 × 105 g polyethylene (mol metal)−1 h−1 atm−1 are afforded, and the most active catalysts are those with methyl in both ortho‐ and para‐positions of the imine N‐aryl ring. For bis(imino)pyridyl–Co(II) and Ni(II) catalysts bearing the SO42− and NO3− counter‐anions, the low activities for ethylene oligomerization are in sharp contrast to those of their chloride analogues. Copyright © 2009 Society of Chemical Industry