Neutral Analogues Research Articles

Abstract 2663: Regulation of ER stress-mediated cell death by calcium mobilization: A potential mitochondrial pathway for 15-deoxy-Δ12,14prostamide J2cytotoxicity in melanoma

Abstract Melanoma is the most aggressive and deadly form of cutaneous cancer in the United States, representing a major clinical challenge. Our lab previously demonstrated that the endocannabinoid metabolite, 15-deoxy, Δ12,14 prostamide J2 (15d-PMJ2), was an effective and selective inducer of apoptotic cell death in B16F10 murine melanoma cells. Furthermore, we found that 15d-PMJ2 mediated apoptosis was regulated by endoplasmic reticulum (ER) stress. Numerous studies have determined that ER stress causes Ca+2 flux, and that this action initiates cellular apoptosis. As such, we investigated Ca+2 mobilization in the context of 15d-PMJ2-mediated ER stress. In B16F10 melanoma cells, 15d-PMJ2 significantly increased cytosolic Ca+2 levels. Blockade of Ca+2 channels using ruthenium red (a pan Ca+2 channel inhibitor) or 2-APB (an IP3 selective inhibitor) decreased the cytotoxicity of 15d-PMJ2. To investigate the role of ER stress in Ca+2 mobilization, cells were pretreated with the ER stress inhibitors, phenylbutyric acid (PBA) and GSK2602 (a PERK-selective inhibitor). Both inhibitors significantly lowered cytosolic Ca+2 levels suggesting Ca+2 flux is mediated by ER stress. Moreover, BAP31, an important regulator of endoplasmic Ca+2 release and ER stress was activated following exposure to 15d-PMJ2. To understand the impact of elevated Ca+2 levels, we investigated cysteine proteases (calpains) and mitochondrial Ca+2, both of which induce apoptosis in a Ca+2-dependent manner. Our results show that mitochondrial Ca+2 levels were significantly increased by 15d-PMJ2 and that this effect was prevented by blocking ER stress. In contrast, 15d-PMJ2 increased calpain-2 activity however, the inhibition of calpain had no effect on the cytotoxicity of 15d-PMJ2. These findings indicate that mitochondrial Ca2+ flux, but not calpains regulate ER stress apoptosis induced by 15d-PMJ2. It has been reported that the activity of J-series prostaglandins is conferred by an electrophilic double bond contained within its cyclopentenone ring. To evaluate the significance of this moiety in 15d-PMJ2, a neutral analog (neutral-15d-PMJ2) lacking the double bond was synthesized. We determined that that the accumulation of intracellular and mitochondrial Ca2+ was dependent on the electrophilic double bond, suggesting it is a critical structural component required for activity. Taken together, these data indicate that the mobilization of calcium to the cytoplasm and mitochondria may critically regulate ER stress apoptosis that is mediated by 15d-PMJ2. Citation Format: Daniel Alexander Ladin, Estefani Cota, Rukiyah Van Dross. Regulation of ER stress-mediated cell death by calcium mobilization: A potential mitochondrial pathway for 15-deoxy-Δ12,14prostamide J2cytotoxicity in melanoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2663.

Beyond Oxides: Nitride as a Ligand in a Neutral IrIXNO3 Molecule Bearing a Transition Metal at High Oxidation State

Theoretical calculations utilizing relativistic ZORA Hamiltonian point to the conceivable existence of an IrNO3 molecule in C3v geometry. This minimum is shown to correspond to genuine nonavalent iridium nitride trioxide, which is a neutral analogue of cationic [IrO4 ]+ species detected recently. Despite the presence of nitride anion, the molecule is protected by substantial barriers exceeding 200 kJ mol-1 against transformations leading, for example, to global minimum (O=)2 Ir-NO, which contains metal at a lower formal oxidation state.

Apelin protects against abdominal aortic aneurysm and the therapeutic role of neutral endopeptidase resistant apelin analogs.

Abdominal aortic aneurysm (AAA) remains the second most frequent vascular disease with high mortality but has no approved medical therapy. We investigated the direct role of apelin (APLN) in AAA and identified a unique approach to enhance APLN action as a therapeutic intervention for this disease. Loss of APLN potentiated angiotensin II (Ang II)-induced AAA formation, aortic rupture, and reduced survival. Formation of AAA was driven by increased smooth muscle cell (SMC) apoptosis and oxidative stress in Apln-/y aorta and in APLN-deficient cultured murine and human aortic SMCs. Ang II-induced myogenic response and hypertension were greater in Apln-/y mice, however, an equivalent hypertension induced by phenylephrine, an α-adrenergic agonist, did not cause AAA or rupture in Apln-/y mice. We further identified Ang converting enzyme 2 (ACE2), the major negative regulator of the renin-Ang system (RAS), as an important target of APLN action in the vasculature. Using a combination of genetic, pharmacological, and modeling approaches, we identified neutral endopeptidase (NEP) that is up-regulated in human AAA tissue as a major enzyme that metabolizes and inactivates APLN-17 peptide. We designed and synthesized a potent APLN-17 analog, APLN-NMeLeu9-A2, that is resistant to NEP cleavage. This stable APLN analog ameliorated Ang II-mediated adverse aortic remodeling and AAA formation in an established model of AAA, high-fat diet (HFD) in Ldlr-/- mice. Our findings define a critical role of APLN in AAA formation through induction of ACE2 and protection of vascular SMCs, whereas stable APLN analogs provide an effective therapy for vascular diseases.

DNA replication studies of N-nitroso compound–induced O6-alkyl-2′-deoxyguanosine lesions in Escherichia coli

N-Nitroso compounds (NOCs) are common DNA-alkylating agents, are abundantly present in food and tobacco, and can also be generated endogenously. Metabolic activation of some NOCs can give rise to carboxymethylation and pyridyloxobutylation/pyridylhydroxybutylation of DNA, which are known to be carcinogenic and can lead to gastrointestinal and lung cancer, respectively. Herein, using the competitive replication and adduct bypass (CRAB) assay, along with MS- and NMR-based approaches, we assessed the cytotoxic and mutagenic properties of three O6-alkyl-2'-deoxyguanosine (O6-alkyl-dG) adducts, i.e. O6-pyridyloxobutyl-dG (O6-POB-dG) and O6-pyridylhydroxybutyl-dG (O6-PHB-dG), derived from tobacco-specific nitrosamines, and O6-carboxymethyl-dG (O6-CM-dG), induced by endogenous N-nitroso compounds. We also investigated two neutral analogs of O6-CM-dG, i.e. O6-aminocarbonylmethyl-dG (O6-ACM-dG) and O6-hydroxyethyl-dG (O6-HOEt-dG). We found that, in Escherichia coli cells, these lesions mildly (O6-POB-dG), moderately (O6-PHB-dG), or strongly (O6-CM-dG, O6-ACM-dG, and O6-HOEt-dG) impede DNA replication. The strong blockage effects of the last three lesions were attributable to the presence of hydrogen-bonding donor(s) located on the alkyl functionality of these lesions. Except for O6-POB-dG, which also induced a low frequency of G → T transversions, all other lesions exclusively stimulated G → A transitions. SOS-induced DNA polymerases played redundant roles in bypassing all the O6-alkyl-dG lesions investigated. DNA polymerase IV (Pol IV) and Pol V, however, were uniquely required for inducing the G → A transition for O6-CM-dG exposure. Together, our study expands our knowledge about the recognition of important NOC-derived O6-alkyl-dG lesions by the E. coli DNA replication machinery.

Phenolic Bis-styrylbenzo[ c]-1,2,5-thiadiazoles as Probes for Fluorescence Microscopy Mapping of Aβ Plaque Heterogeneity.

A fluorescent bis-styryl-benzothiadiazole (BTD) with carboxylic acid functional groups (X-34/Congo red analogue) showed lower binding affinity toward Aβ1-42 and Aβ1-40 fibrils than its neutral analogue. Hence, variable patterns of neutral OH-substituted bis-styryl-BTDs were generated. All bis-styryl-BTDs showed higher binding affinity to Aβ1-42 fibrils than to Aβ1-40 fibrils. The para-OH on the phenyl rings was beneficial for binding affinity while a meta-OH decreased the affinity. Differential staining of transgenic mouse Aβ amyloid plaque cores compared to peripheral coronas using neutral compared to anionic bis-styryl ligands indicate differential recognition of amyloid polymorphs. Hyperspectral imaging of transgenic mouse Aβ plaque stained with uncharged para-hydroxyl substituted bis-styryl-BTD implicated differences in binding site polarity of polymorphic amyloid plaque. Most properties of the corresponding bis-styryl-BTD were retained with a rigid alkyne linker rendering a probe insensitive to cis-trans isomerization. These new BTD-based ligands are promising probes for spectral imaging of different Aβ fibril polymorphs.

Influence of Gemini Surfactants on Biochemical Profile and Ultrastructure of Aspergillus brasiliensis

In this study, we investigated the activities of hexamethylene-1,6-bis-(N,N-dimethyl-N-dodecylammonium bromide) (C6), pentamethylene-1,5-bis-(N,N-dimethyl-N-dodecylammonium bromide) (C5), and their two neutral analogues: hexamethylene-1,6-bis-(N-methyl-N-dodecylamine) (A6) and pentamethylene-1,5-bis-(N-methyl-N-dodecylamine) (A5) at concentrations of ½ MIC, MIC, and 2 MIC (minimal inhibitory concentration) against hyphal forms of Aspergillus brasiliensis ATCC 16404. Enzymatic profiles were determined using the API-ZYM system. Extracellular proteins were extracted from the mycelia and analyzed using sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). The ultrastructure was evaluated using a transmission electron microscope (TEM). Both groups of surfactants caused changes in the enzyme profiles. Larger changes in the number and concentration of enzymes were noted after the action of non-ionic gemini surfactants, which may have been due to the 100× higher concentration of neutral compounds. Larger differences between the protein profiles of the control sample and the biocide samples were observed following the use of cationic compounds. On the basis of TEM analyses, we found that, with increasing concentrations of compound C6, the mycelium cells gradually degraded. After treatment at 2 MIC, only membranous structures, multiform bodies, and dense electron pellets remained. Based on these results, we concluded that cationic gemini surfactants, in comparison with their non-ionic analogues, could have a wide range of practical applications as active compounds.

Synergetic improvements of sensitivity and specificity of nanowire field effect transistor gene chip by designing neutralized DNA as probe

Neutral DNA analogs as probes for the detection of target oligomers on the biosensors based on the field-effect transistor (FET) configuration feature advantages in the enhancement of sensitivity and signal-to-noise ratio. Herein, we used phosphate-methylated nucleotides to synthesize two partially neutralized chimeric DNA products and a fully neutralized DNA sequence and adopted a regular DNA oligomer as probes on the polycrystalline silicon nanowire (NW) FET devices. The sequences of two neutralized chimeric DNAs close to the 5′ end were alternately modified with the phosphate-methylated nucleotides, and all probes were immobilized via their 5′ end on the NW surface. The non-specific-to-specific binding ratio indicated that the two 5′-end partially neutralized chimeric DNAs featured better performance than the regular and fully neutralized DNA oligomers. The partially neutralized probe design reduces the ionic strength needed for hybridization and increases the Debye length of detection, thus promoting the detection sensitivity of FET and achieving the limit of detection of 0.1 fM. By using an appropriate probe design, applying DNA oligomers with embedded phosphate-methylated nucleotides in the FET biosensors is a promising way for gene detection with high sensitivity and specificity.

C–H Bond Activation by a Ruthenium(II) β‐Diketonate Complex: A Mechanistic Study

Ruthenium(II)‐catalysed C–H bond activation of arenes containing a functional directing group depends on the ligand coordinated to ruthenium(II). In this study, 2‐phenylpyridine C–H activation catalysed by a “piano‐stool“ ruthenium(II) complex containing a fluorinated β‐diketonate ligand was examined by ESI‐MS in combination with CID experiments. [Ru(β‐diketonate)(CTPhPy)Cl]+ was identified as an active intermediate, and its collisional activation leads to C–H activation. CID analysis indicates proton transfer from the phenylpyridine to the chlorine anion, showing HCl elimination, while the β‐diketonate ligand is retained in the complex together with the activated phenylpyridine. Furthermore, DFT calculations were performed for the neutral analogue [Ru(β‐diketonate)(PhPy)Cl] to identify all ruthenium intermediates along the C–H activation reaction pathway. The results suggest that the most stable structure of [Ru(β‐diketonate)(PhPy)Cl] has pre‐activated 2‐phenylpyridine with a partly developed Ru–H bond. Further, we show that K2CO3 is not directly involved in the C–H activation step and it serves in the reaction as a base.

Incorporation of Metallic Species into Midblock-Sulfonated Block Ionomers.

Block ionomers can, in the same fashion as their neutral block copolymer analogs, microphase-order into various nanoscale morphologies. The added benefit of a copolymer possessing a charged species is that the resultant block ionomer becomes amphiphilic and capable of imbibing polar liquids, including water. This characteristic facilitates incorporation of metallic species into the soft nanostructure for a wide range of target applications. In this study, the nonpolar and polar constituents of solvent-templated midblock-sulfonated block ionomers (SBIs) are first selectively metallated for complementary morphological analysis. Next, four different salts, with cationic charges ranging from +1 to +3, are introduced into three hydrated SBIs varying in their degree of sulfonation (DOS), and cation uptake is measured as a function of immersion time. These results indicate that uptake generally increases with increasing salt concentration, cationic charge, and specimen DOS. Swelling and nanoindentation measurements conducted at ambient temperature demonstrate that water uptake decreases, while the surface modulus increases, with increasing cationic charge. Chemical spectra acquired from energy-dispersive X-ray spectroscopy (EDS) confirm the presence of each of the ion-exchanged species, and corresponding EDS chemical maps reveal that the spatial distribution of these species is relatively uniform throughout the block ionomer films.

Force Field Benchmark of Amino Acids. 2. Partition Coefficients between Water and Organic Solvents.

2018 , 58 , 1037 - 1052 ), may aid in the development and systematic improvements of classical force fields to model proteins in aqueous and nonaqueous phases accurately.

Rearrangements in radical cations of diazoketones: A DFT mechanistic study

Abstract The mechanism of the Wolff rearrangement of some radical cations of diazocarbonyl compounds has been studied using density functional calculations. The C C bond of diazoketones weakens slightly on cation formation, which lowers the barrier to the syn-anti isomerization of the radical cations, as compared to that of the neutral analogue. The effect of substitution on both carbonyl carbon and diazocarbon of the diazoethanal radical cation has been explored. The planarity of the syn and anti conformers is lost on reduction of diazoketones, and in most of the cases of substitution at the carbonyl carbon, the diazo moiety is out of the plane of the C O group. The 1, 2-rearrangement of radical cations preferably takes place in a stepwise manner, which involves the oxirene radical cation as an intermediate. The oxirene radical cation rearranges to the final product, the ketene radical cation, without any energy barrier. However, the carbene radical cation is involved in the Wolff rearrangement of the diazoethanal radical cation substituted at the diazocarbon atom by Ph, OMe or NH2.

Synthesis and in vitro PDT evaluation of new porphyrins containing meso-epoxymethylaryl cationic groups.

Photodynamic therapy (PDT) is an effective cancer treatment that uses photosensitizers, light, and oxygen to destroy malignant cells. Porphyrins, and in particular the cationic derivatives, are the most investigated photosensitizers for PDT. In this context, it is important to study new methodologies to develop efficient cationic photosensitizers for use in PDT. New porphyrins bearing cationic epoxymethylaryl groups were synthesized and characterized. Their cellular uptake, intracellular localization, and phototoxicity were evaluated in human HEp2 cells, and compared with their methylated analogs. All cationic porphyrins were efficient generators of singlet oxygen, with quantum yields in the range 0.35-0.61. The two methylated derivatives (3 and 4) accumulated the most within cells at all times investigated, up to 24 hours. Of these two porphyrins, 4 was the most phototoxic to the cells (LD50 = 2.4 μM at 1.5 J/cm2 ); however, porphyrin 3 also showed high phototoxicity (LD50 = 7.4 μM at 1.5 J/cm2 ). The epoxymethyl-containing porphyrins were found to be less phototoxic than the methylated derivatives, with LD50 > 38 μM. The neutral porphyrins showed no phototoxicity up to the 100 μM concentrations investigated, and had the lowest singlet oxygen quantum yields. All cationic porphyrins localized mainly in the cell ER, Golgi apparatus, and lysosomes. Our results suggest that cationic methylated porphyrin derivatives are promising PDT photosensitizing agents. The epoxymethyl-containing derivatives showed increased efficacy relative to the neutral analogs, and are good candidates for further investigation. Lasers Surg. Med. 50:566-575, 2018. © 2018 Wiley Periodicals, Inc.

Force Field Benchmark of Amino Acids: I. Hydration and Diffusion in Different Water Models.

Thermodynamic and kinetic properties are of critical importance for the applicability of computational models to biomolecules such as proteins. Here we present an extensive evaluation of the Amber ff99SB-ILDN force field for modeling of hydration and diffusion of amino acids with three-site (SPC, SPC/E, SPC/Eb, and TIP3P), four-site (TIP4P, TIP4P-Ew, and TIP4P/2005), and five-site (TIP5P and TIP5P-Ew) water models. Hydration free energies (HFEs) of neutral amino acid side chain analogues have little dependence on the water model, with a root-mean-square error (RMSE) of ∼1 kcal/mol from experimental observations. On the basis of the number of interacting sites in the water model, HFEs of charged side chains can be putatively classified into three groups, of which the group of three-site models lies between those of four- and five-site water models; for each group, the water model dependence is greatly eliminated when the solvent Galvani potential is considered. Some discrepancies in the location of the first hydration peak ( RRDF) in the ion-water radial distribution function between experimental and calculated observations were detected, such as a systematic underestimation of the acetate (Asp side chain) ion. The RMSE of calculated diffusion coefficients of amino acids from experiment increases linearly with the increasing diffusion coefficients of the solvent water models at infinite dilution. TIP3P has the fastest diffusivity, in line with literature findings, while the "FB" and "OPC" water model families as well as TIP4P/2005 perform well, within a relative error of 5%, and TIP4P/2005 yields the most accurate estimate for the water diffusion coefficient. All of the tested water models overestimate amino acid diffusion coefficients by approximately 40% (TIP4P/2005) to 200% (TIP3P). Scaling of protein-water interactions with TIP4P/2005 in the Amber ff99SBws and ff03ws force fields leads to more negative HFEs but has little influence on the diffusion of amino acids. The most recent FF/water combinations of ff14SB/OPC3, ff15ipq/SPC/Eb, and fb15/TIP3P-FB do not show obvious improvements in accuracy for the tested quantities. These findings here establish a benchmark that may aid in the development and improvement of classical force fields to accurately model protein dynamics and thermodynamics.

Impact of Cationic and Neutral Gemini Surfactants on Conidia and Hyphal Forms of Aspergillus brasiliensis.

This study investigates the biological activity of two cationic gemini surfactants, hexamethylene-1,6-bis-(N,N-dimethyl-N-dodecylammonium bromide) C6 and pentamethylene-1,5-bis-(N,N-dimethyl-N-dodecylammonium bromide) C5, and their two neutral analogs, hexamethylene-1,6-bis-(N-methyl-N-dodecylamine) (A6) and pentamethylene-1,5-bis-(N-methyl-N-dodecylamine) (A5). Experiments were performed with Aspergillus brasiliensis, which is used in the standard tests for biocides. The minimal inhibitory concentration (MIC) values for conidia and mycelium were determined using the dilution method. The viability of the conidia was evaluated using the plate count method. The dry mass of the mycelium was determined using the thermogravimetric method. Ergosterol was extracted from the mycelium and evaluated by gas chromatography. The effect of gemini surfactants on fungal morphology was observed using scanning electron microscopy. Cationic gemini surfactants were found to be active at lower concentrations compared to their non-ionic analogues, rapidly reducing the total number of conidia that were able to grow. They also decreased both the ergosterol content in the mycelium and its dry weight. These results suggest that cationic gemini surfactants C6 and C5 could have a wide range of practical applications as active compounds. However, it should be remembered that usage at too low concentrations, below the MIC, will only lead to short-term disturbances in the development of conidia and mycelium.

Silyl Ketene Acetals/B(C₆F₅)₃ Lewis Pair-Catalyzed Living Group Transfer Polymerization of Renewable Cyclic Acrylic Monomers.

This work reveals the silyl ketene acetal (SKA)/B(C6F5)3 Lewis pair-catalyzed room-temperature group transfer polymerization (GTP) of polar acrylic monomers, including methyl linear methacrylate (MMA), and the biorenewable cyclic monomers γ-methyl-α-methylene-γ-butyrolactone (MMBL) and α-methylene-γ-butyrolactone (MBL) as well. The in situ NMR monitored reaction of SKA with B(C6F5)3 indicated the formation of Frustrated Lewis Pairs (FLPs), although it is sluggish for MMA polymerization, such a FLP system exhibits highly activity and living GTP of MMBL and MBL. Detailed investigations, including the characterization of key reaction intermediates, polymerization kinetics and polymer structures have led to a polymerization mechanism, in which the polymerization is initiated with an intermolecular Michael addition of the ester enolate group of SKA to the vinyl group of B(C6F5)3-activated monomer, while the silyl group is transferred to the carbonyl group of the B(C6F5)3-activated monomer to generate the single-monomer-addition species or the active propagating species; the coordinated B(C6F5)3 is released to the incoming monomer, followed by repeated intermolecular Michael additions in the subsequent propagation cycle. Such neutral SKA analogues are the real active species for the polymerization and are retained in the whole process as confirmed by experimental data and the chain-end analysis by matrix-assisted laser desorption/ionization time of flight mass spectroscopy (MALDI-TOF MS). Moreover, using this method, we have successfully synthesized well-defined PMMBL-b-PMBL, PMMBL-b-PMBL-b-PMMBL and random copolymers with the predicated molecular weights (Mn) and narrow molecular weight distribution (MWD).

Measurement of e+e−→π0π0ψ(3686) at s from 4.009 to 4.600 GeV and observation of a neutral charmoniumlike structure

Using $e^{+}e^{-}$ collision data collected with the BESIII detector at the BEPCII collider corresponding to an integrated luminosity of 5.2 $fb^{-1}$ at center-of-mass energies ($\sqrt{s}$) from 4.009 to 4.600 GeV, the process $e^{+}e^{-} \to \pi^{0} \pi^{0}\psi(3686)$ is studied for the first time. The corresponding Born cross sections are measured and found to be half of those of the reaction $e^{+}e^{-} \to \pi^{+}\pi^{-}\psi(3686)$. This is consistent with the expectation from isospin symmetry. Furthermore, the Dalitz plots for $\pi^{0}\pi^{0}\psi(3686)$ are accordant with those of $\pi^{+}\pi^{-}\psi(3686)$ at all energy points, and a neutral analogue to the structure in $\pi^\pm \psi(3686)$ around 4040 MeV/$c^{2}$ first observed at $\sqrt{s}$=4.416 GeV is observed in the isospin neutral mode at the same energy.

Synthetic Chlorophyll-A Derivatives Stabilize DNA G-Quadruplex Structures

A DNA G-quadruplex structure is one of the higher-order DNA structures found in a telomere region of chromosomes and suppresses enzymatic telomere-elongation reactions which frequently occur in cancer cells. Therefore, ligand compounds stabilizing such a DNA G-quadruplex structure is expected as a new-type of anti-cancer agents. To evaluate the interaction of the ligand with DNA G-quadruplexes in an aqueous solution, the examined ligands must be highly water-soluble. Such ligands have been usually substituted with hydrophilic substituents in a molecule. Here we report synthesis of several chlorophyll-a derivatives, in which their inner nitrogen is methylated, to enable their complexation and stabilization with a DNA G-quadruplex in an aqueous solution. Their binding constants with the DNA G-quadruplex structure were determined by optical spectroscopic techniques. The values using cationic N-methylated chlorophyll-a derivatives were larger than those using neutral unmethylated analogs. In addition, the thermodynamic stabilities of several G-quadruplexes with the synthetic ligands were analyzed by CD spectroscopy and will be discussed.

Site-Specific Encoding of Citrulline, a Neutral Analog of Arginine, to Study the Atomic Basis for Voltage-Dependent Gating In Ion Channels

Site-Specific Encoding of Citrulline, a Neutral Analog of Arginine, to Study the Atomic Basis for Voltage-Dependent Gating In Ion Channels

Functional groups ionization effect on conformational properties of dendritic molecular brushes

Conformational properties of dendronized molecular brushes with ionized terminal groups in the dilute solution were studied by the Scheutjens-Fleer numerical self-consistent field method. Brushes with the same molecular mass and grafting density of dendrons but different generation number were compared. The ionic strength was varied within the conditions of the good (athermal) solvent. It was shown that the brush thickness increases with the ionic strength decrease as a result of the deformation of grafted dendrons. The induced persistence length, which characterizes the contribution of the grafted branches into the bending elasticity of the brush, behaves differently at large and small ionic strengths. At high salt concentration the brushes with more branched dendrons show smaller bending elasticity similar to their neutral analogs. At low ionic strengths the induced persistence length increases by an order and depends very weakly on the dendron architecture.

Syntheses of Amino-Substituted Iridabenzofurans and Subsequent Selective N-Functionalisation.

The first examples of amino-substituted fused-ring metallabenzenes, the cationic iridabenzofuran [Ir(C7 H4 O{NH2 -2}{OMe-7})(CO)(PPh3 )2 ][O3 SCF3 ] (5) and neutral analogue Ir(C7 H4 {NH2 -2}{OMe-7})Cl(PPh3 )2 (6), can be prepared by reduction of the corresponding nitro-substituted iridabenzofurans with zinc and concentrated hydrochloric acid. N-functionalised derivatives of 5 and 6 are formed through alkylation, sulfonylation or acylation. Thus, consecutive treatments with methyl triflate and base gives the corresponding trimethylammonium-substituted iridabenzofurans while sulfonamide derivatives are formed with p-toluenesulfonyl chloride. N-Acylation of 5 or 6 with acid chlorides, however, selectively form either amide or imide products depending on the charge on the metal and the steric size of the acid chloride. Cationic 5 gives amide substituted products regardless of the conditions whereas neutral 6 rapidly undergoes di-N-acylation with excess benzoyl chloride under mild conditions to give the imide-substituted product Ir(C7 H4 O{N[C(O)Ph]2 -2}{OMe-7})Cl(PPh3 )2 (13). Selective mono-acylation of 6 can be achieved with one equivalent of benzoyl chloride or with excess of the sterically congested pivaloyl chloride.