Flexible Substituents Research Articles

Subtle Steric Effects in Nickel‐Catalysed Kumada–Tamao–Corriu Cross‐Coupling Using Resorcinarenyl‐Imidazolium Salts

AbstractThree resorcinarene‐cavitands bearing a 3‐R‐1‐imidazolylium substituent (R = alkyl) grafted to the wider rim of the cavitand (1–3) were assessed in the Kumada–Tamao–Corriu cross‐coupling of aryl halides with arylmagnesium halides. Their combination with [Ni(cod)2] (cod = 1,5‐cyclooctadiene; 1:1 stoichiometry) resulted in highly efficient catalysts, the activities of which varied in the following order: R = n‐propyl (1) < isopropyl (2) ≈ benzyl (3). A remarkable turnover frequency of 60400 mol(ArX) mol(Ni)–1 h–1 was obtained in the coupling of 2‐bromo‐6‐methoxynaphthalene with PhMgBr (100 °C in dioxane, with precursor 2). The high activities of the cavitand derivatives were attributed to steric effects that facilitate the reductive‐elimination/product decoordination step. Comparative experiments carried out with a structurally modified resorcinarene, as well as cavity‐free imidazolium salts bearing 2‐methoxyaryl substituents, suggest that the efficiency of the catalysts mainly relies on steric interactions between the metal and the flexible substituents attached to two methine carbon atoms. These steric interactions are probably reinforced each time the metal binds one of the two oxygen atoms located next to the catalytic centre.

Syntheses of two imidazolate-4-amide-5-imidate linker-based hexagonal metal–organic frameworks with flexible ethoxy substituent

A rare example of in situ linker generation with the formation of soft porous Zn- and Co-MOFs (IFP-9 and -10, respectively) is reported. The flexible ethoxy groups of IFP-9 and -10 protrude into the 1D hexagonal channels. The gas-sorption behavior of both materials for H2, CO2 and CH4 showed wide hysteretic isotherms, typical for MOFs having a flexible substituent which can give rise to a gate effect.

Phosphane‐Mediated Domino Synthesis of Tetrasubstituted Furans from Simple Terminal Activated Olefins

AbstractConvenient and highly efficient syntheses of tetrasubstituted furans with flexible substituent patterns from simple and readily available starting materials have been developed. Under very mild conditions, with the mediation of stoichiometric nBu3P, simple terminal activated olefins and acyl chlorides or anhydrides smoothly furnish tetrasubstituted furans in modest to excellent yields. This synthetic strategy features a flexible selection of substituent pattern and a C‐acylation/O‐acylation/C‐acylation/intramolecular Wittig reaction multiple domino assembly sequence.

Isothermally Reversible Fluorescence Switching of a Mechanochromic Perylene Bisimide Dye

Isothermally rewritable fluorescence mechanochromism has been realized for a perylene bisimide dye with bulky and flexible substituents. Fluorescent patterns drawn by mechanical stimuli can be erased by thermal stimuli, treatment with solvent vapors, or spontaneous structural transition from orange-fluorescent to green-fluorescent states. The isothermal fluorescence switching of solid dye films is applicable to displays and sensory materials.

Directing the Breathing Behavior of Pillared-Layered Metal–Organic Frameworks via a Systematic Library of Functionalized Linkers Bearing Flexible Substituents

Flexible metal-organic frameworks (MOFs), also referred to as soft porous crystals (SPCs), show reversible structural transitions dependent on the nature and quantity of adsorbed guest molecules. In recent studies it has been reported that covalent functionalization of the organic linker can influence or even integrate framework flexibility ("breathing") in MOFs. However, rational fine-tuning of such responsive properties is very desirable but challenging as well. Here we present a powerful approach for the targeted manipulation of responsiveness and framework flexibility of an important family of pillared-layered MOFs based on the parent structure [Zn(2)(bdc)(2)(dabco)](n) (bdc = 1,4-benzenedicarboxylate; dabco = 1,4-diazabicyclo[2.2.2]octane). A library of functionalized bdc-type linkers (fu-bdc), which bear additional dangling side groups at different positions of the benzene core (alkoxy groups of varying chain length with diverse functionalities and polarity), was generated. Synthesis of the materials [Zn(2)(fu-bdc)(2)(dabco)](n) yields the respective collection of highly responsive MOFs. The parent MOF is only weakly flexible; however, the substituted frameworks of [Zn(2)(fu-bdc)(2)(dabco)](n) contract drastically upon guest removal and expand again upon adsorption of DMF (N,N-dimethylformamide), EtOH, or CO(2), etc., while N(2) is hardly adsorbed and does not open the narrow-pored form. These "breathing" dynamics are attributed to the dangling side chains that act as immobilized "guests", which interact with mobile guest molecules as well as with themselves and with the framework backbone. The structural details of the guest-free, contracted form and the gas sorption behavior (phase transition pressure, hysteresis loop) are highly dependent on the nature of the substituent at the linker and can therefore be adjusted using our approach. Combining our library of functionalized linkers with the concept of mixed-component MOFs (solid solutions) offers very rich additional dimensions of tailoring the structural dynamics and responsiveness. Implementation of two differently functionalized linkers in varying ratios yields multicomponent single-phased [Zn(2)(fu-bdc')(2x)(fu-bdc″)(2-2x)(dabco)](n) MOFs (0 < x < 1) of increased inherent complexity, which feature a non-linear dependence of their gas sorption properties on the applied ratio of components. Hence, the responsive behavior of such pillared-layered MOFs can be extensively tuned via an intelligent combination of functionalized linkers.

Tuning N‐Heterocyclic Carbenes in T‐Shaped PtII Complexes for Intermolecular CH Bond Activation of Arenes

Small change matters: T-shaped Pt(II) complexes with less flexible substituents, than, for example, isopropyl or tert-butyl groups, on N-heterocyclic carbene (NHC) ligands allow for C-H bond activation reactions of aromatic compounds (see scheme; BAr(f)(4)(-) =tetrakis[(3,5-trifluoromethyl)phenyl]borate; F yellow, Pt red). NHC substituents that are not highly branched prevent agostic interactions and reduce the barriers to achieve the C-H bond cleavage.

Role of Ligand Reorganization and Conformational Restraints on the Binding Free Energies of DAPY Non-Nucleoside Inhibitors to HIV Reverse Transcriptase

The results of computer simulations of the binding of etravirine (TMC125) and rilpivirine (TMC278) to HIV reverse transcriptase are reported. It is confirmed that consistent binding free energy estimates are obtained with or without the application of torsional restraints when the free energies of imposing the restraints are taken into account. The restraints have a smaller influence on the thermodynamics and apparent kinetics of binding of TMC125 compared to the more flexible TMC278 inhibitor. The concept of the reorganization free energy of binding is useful to understand and categorize these effects. Contrary to expectations, the use of conformational restraints did not consistently enhance convergence of binding free energy estimates due to suppression of binding/unbinding pathways and due to the influence of rotational degrees of freedom not directly controlled by the restraints. Physical insights concerning the thermodynamic driving forces for binding and the role of "jiggling" and "wiggling" motion of the ligands are discussed. Based on these insights we conclude that an ideal inhibitor, if chemically realizable, would possess the electrostatic charge distribution of TMC125, so as to form strong interactions with the receptor, and the larger and more flexible substituents of TMC278, so as to minimize reorganization free energy penalties and the effects of resistance mutations, suitably modified, as in TMC125, so as to disfavor the formation of non-binding competent extended conformations when free in solution.

Hydrothermal Synthesis, Structural Determination, and Properties of a New Family of Mononuclear Lanthanide Complexes with Pyridines Bearing More Flexible Pendant-Arm Carboxylate Substituents

Members of a new family of mononuclear lanthanide complexes possessing the general formula Ln(3-pyrac)3(H2O)3 (Ln = Y 1, La 2, Sm 3, Eu 4, Gd 5, Tb 6, Dy 7, Er 8, 3-pyrac = 3-pyridylacetate) were synthesized by hydrothermal reaction and characterized by single-crystal x-ray diffraction analysis, infrared (IR) spectra, luminescent spectroscopy, and thermal analysis. Photoluminescence measurement indicates that the complexes 3, 4, 6, and 7 exhibit characteristic emission of Sm(III), Eu(III), Tb(III), and Dy(III) at room temperature. The electrochemical behavior of complexes 4 has been examined by cyclic voltammetry in aqueous solution.

Meso-diacylated calix[4]pyrrole: structural diversities and enhanced binding towards dihydrogenphosphate ion

Meso-diacylated calix[4]pyrrole was obtained via acid catalysed condensation of meso-acylated dipyrromethane with acetone. Selective presence of flexible substituents at the calix[4]pyrrole periphery led to interesting structural motifs in the solid state along with enhanced binding towards anions, especially dihydrogenphosphate ion via anchoring.

Synthesis and properties of mesogen-jacketed liquid crystalline polymers containing bistolane mesogen

On the basis of the concept of mesogen-jacketed liquid crystalline polymers, a series of new methacrylate monomers, (2,5-bis[2-(4′-alkoxyphenyl) ethynyl] benzyl methacrylate (MACn, n = 4, 6, 8, 10, and 12) and 2,5-bis[2-(6′-decanoxynaphthyl) ethynyl] benzyl methacrylate (MANC10), and their polymers, PMACn (n = 4, 6, 8, 10, and 12) and PMANC10 were synthesized. The bistolane mesogen with large π-electron conjugation were side-attached to the polymer backbone via short linkages. Various characterization techniques such as differential scanning calorimetry, wide-angle X-ray diffraction, and polarized light microscopy were used to study their mesomorphic phase behavior. The polymer PMACn with shorter flexible substituents (n = 4) forms the columnar nematic (ϕN) phase, but other polymers with longer flexible tails (n = 6, 8, 10, and 12) can develop into a smetic A (SA) phase instead of a ϕN phase. The PMANC10 containing naphthyl can also form a well-defined SA phase. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2010

ChemInform Abstract: Very Strong Inhibition of Glucosidases by C(2)-Substituted Tetrahydroimidazopyridines.

The C(2)-substituted imidazoles 11, 15 – 17, 19, 21, 23/24, 28 – 31, 37, and 38 have been prepared from the known 2,3-unsubstituted imidazole 7via the iodoimidazole 10, and tested as inhibitors of β- and α-glucosidases. Introduction of hydrophobic and flexible substituents, such as in 28 and 29, led to a very strong inhibition of β-glucosidases, with Ki values for 29 of 1.2 and 0.11 nM against β-glucosidases from almonds and Caldocellum saccharolyticum, respectively. A slow onset of the inhibition was observed for the strongly inhibiting 16, 28 – 31, 37, and 38. While the introduction of a hydroxymethyl or a phenethyl substituent as in 17 and 30 led to stronger inhibition, the 1′-hydroxyphenethyl derivatives 37 and 38 were weaker inhibitors than 16 and 29. This result is interpreted in the light of a conformational change of the substrate on the way to the transition state. The substituent at C(2) has only a moderate influence on the selectivity of the inhibition of two β- and one α-glucosidases, increasing it by a maximal factor of ca. 10 (16), or decreasing it by a maximal factor of ca. 15 (37).

Comparative Analysis of IR and Vibrational Circular Dichroism Spectra for a Series of Camphor-Related Molecules

The absorption spectra and vibrational circular dichroism (VCD) spectra in the mid-IR range 1600-950 cm(-1) of 10 camphor-related compounds have been recorded and compared to DFT calculated spectra at the B3PW91/TZ2P level and have been examined together with the corresponding data of the parent molecules. The rigidity of the bridged structure common to all compounds investigated permits (a) identification of three spectroscopic regions in the mid-IR range that can be "used" separately by the interested stereochemist for structural diagnosis and assignment of some major characteristics of the VCD spectra in these regions to what we call "skeletal chiral sense" and (b) recognition of possible conformers for flexible substituent groups, when present. VCD spectra of the 10 molecules have been recorded and analyzed also in the CH-stretching region, 3100-2800 cm(-1). Here, we have been able to identify and characterize features of vibrational excitons by comparison of data within the 10-molecule class. To find a theoretical justification of result (a), we have examined the potential energy distribution of the normal modes in the mid-IR range, the partitioning of the calculated rotational strengths in terms of contributions from all couples of internal coordinates, the angle formed by the two vectors, the electric dipole transition moment and the magnetic dipole transition moment, and finally the overlap of normal modes of different molecules. A discussion is provided as to the usability of the introduced algorithms.

Novel amides and Schiff's bases derived from 1,3,4-oxadiazole derivatives: synthesis and mesomorphic behaviour

The synthesis and liquid crystalline properties of novel achiral amides (Ia–g, IIa–g and IVa,b), achiral Schiff's bases (IIIa–g and Va–g), chiral amides (VI, VII) and chiral Schiff's bases (VIII–XI) incorporating a 1,3,4-oxadiazole ring are reported. All amides of the series I and II display an enantiotropic smectic A phase. The amide IVa,b did not show mesomorphic properties. Amides of the series Ia–g and IIa–g contain a flexible n-tetradecylthio chain, the other terminal substituent is an n-alkoxy chain and n-alkyl chain, respectively (n = 4–10) and the 1,3,4-oxadiazole is in the terminal rigid core. Amides Ia–g have broader mesomorphic range and higher thermal stability than the corresponding amides IIa–g. Amides IVa,d contain the 1,3,4-oxadiazole ring in the centre of the rigid core and two flexible alkoxy chains as flexible terminal substituents. Thus, the mesomorphic properties are favoured if 1,3,4-oxadiazole is shifted to a terminal position of the rigid core. Schiff's bases IIIa–g display an enantiotropic dimorphism smectic C–smectic A. Schiff's bases IIIa–g have a broader mesomorphic range than the analogous amides Ia–g. Schiff's bases Va–g exhibit a dimorphism smectic A–nematic, and in contrast to this the analogous amide IVa,b did not show mesomorphism. The chiral amides VI and VII and chiral Schiff's bases X and XI did not show mesomorphic properties and only the chiral Schiff's bases VIII and IX display a chiral smectic C phase in a short mesomorphic range. A density functional theory theoretical study at the B3LYP/6–311++G(d,p) level was performed in order to analyse the structural features that must be related with the mesomorphic behaviour of the reported compounds.

Influence of alkoxy tail length and unbalanced mesogenic core on phase behavior of mesogen‐jacketed liquid crystalline polymers

AbstractWhen the flexible terminal substituent changes from butoxy to hexyloxy or longer, smectic C (SC) liquid crystalline phase was firstly reported to develop from a kind of mesogen‐jacketed liquid crystalline polymer (MJLCP) whose mesogenic side groups are unbalancedly bonded to the main chain without spacers. A series of MJLCPs, poly[4,4′‐bis(4‐alkoxyphenyl)‐2‐vinylbiphenyl(carboxide)] (nC2Vp, n is the number of the carbons in the alkoxy groups, n = 2, 4, 6, 8, 10, and 12) were designed and synthesized successfully via free radical polymerization. The molecular weights of the polymers were characterized with gel permeation chromatography, and the liquid crystalline properties were investigated by differential scanning calorimetry, polarized light microscopy experiments, and 1D, 2D wide‐angle X‐ray diffraction. Comparing with the butoxy analog, the polymer with unbalanced mesogenic core and shorter flexible substituents (n = 2, 4) keeps the same smectic A (SA) phase, but other polymers with longer terminal flexible substituents (n = 6, 8, 10, and 12) can develop into a well‐defined SC phase instead of SA phase. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 505–514, 2009

Microwave assisted solventless synthesis of melamines with flexible aromatic substituents

A fast, highly efficient and environmentally friendly solvent-free procedure under microwave irradiation, using silica gel supported reagents for the synthesis of melamines with flexible aromatic N-substituents is developed. It is shown that both microwaves and silica gel accelerate the transformation studied. The synthetic approach presented herein has several advantages. It is a low cost protocol as using the cheap and easily available starting material, cyanuric chloride. The conversion is complete within 3 min, which leads to a serious energy saving. Hydrogen chloride is the only by-product, which makes the procedure an atom economy benign. This by- product is quenched as ammonium salts during the reaction, thus preventing its release into the environment.

Finding a Needle in a Haystack: Development of a Combinatorial Virtual Screening Approach for Identifying High Specificity Heparin/Heparan Sulfate Sequence(s)

We describe a combinatorial virtual screening approach for predicting high specificity heparin/heparan sulfate sequences using the well-studied antithrombin-heparin interaction as a test case. Heparan sulfate hexasaccharides were simulated in the 'average backbone' conformation, wherein the inter-glycosidic bond angles were held constant at the mean of the known solution values, irrespective of their sequence. Molecular docking utilized GOLD with restrained inter-glycosidic torsions and intra-ring conformations, but flexible substituents at the 2-, 3-, and 6-positions and explicit incorporation of conformational variability of the iduronate residues. The approach reproduces the binding geometry of the sequence-specific heparin pentasaccharide to within 2.5 A. Screening of a combinatorial virtual library of 6,859 heparin hexasaccharides using a dual filter strategy, in which predicted antithrombin affinity was the first filter and self-consistency of docking was the second, resulted in only 10 sequences. Of these, nine were found to bind antithrombin in a manner identical to the natural pentasaccharide, while a novel hexasaccharide bound the inhibitor in a unique but dramatically different geometry and orientation. This work presents the first approach on combinatorial library screening for heparin/heparan sulfate GAGs to determine high specificity sequences and opens up huge opportunities to investigate numerous other physiologically relevant GAG-protein interactions.

A discotic triphenylene dimer as organic hole transporting material for electroluminescence devices

A triphenylene dimer, an intermediate between a discotic triphenylene molecule and the macromolecule, had been prepared by linking together two triphenylene units via phenylene carbamate linkages, which was formed through a reaction between one 1,4-phenylene diisocyanate and two hydroxyl end groups on flexible substituents of triphenylenes. The dimer exhibited good film-forming property. Its temperature-dependent phase transitions were investigated using differential scanning calorimetry and polarized optical microscopy. Room temperature microstructure of the dimer was analyzed by X-ray diffraction. Charge mobility of the triphenylene dimer was also measured. Our preliminary result using the materials in a sandwich light-emitting device is reported here. It demonstrates that the triphenylene dimer is a promising candidate as a hole transporting material.

Model studies of the histidine-tyrosine cross-link in cytochrome C oxidase reveal the flexible substituent effect of the imidazole moiety.

[reaction: see text] Experimental and theoretical studies were carried out to interrogate the effect of an imidazole substituent in each of the ortho, meta, and para positions on the pK(a), E degrees , and O-H BDE of phenol. The results reveal that imidazole substitution lowers the pK(a) of phenol and increases the E degrees of phenoxide due to its sigma-electron withdrawing ability (sigma(p)(-) = +0.21, sigma(m)(-) = +0.45) but decreases the O-H BDE and E degrees of phenol due to its pi-electron-donating ability (sigma(p)(+) = -0.45).

Epoxy Networks Reinforced with Polyhedral Oligomeric Silsesquioxanes (POSS). Thermomechanical Properties

The rubbery epoxy network, based on diglycidyl ether of Bisphenol A (DGEBA) and poly(oxypropylene)diamine (Jeffamine D2000), was reinforced with a nanometer-sized inorganic building blockspolyhedral oligomeric silsesquioxanes (POSS). The organic−inorganic networks contained POSS as pendant units of a network chain or as network cross-links of various functionality. Thermomechanical properties and thermal stability of the POSS-containing networks were determined by DMA and TGA. The strongest reinforcement was achieved in the networks with pendant POSS forming ordered crystalline domains, which act as physical cross-links. The POSS skeleton with “soft“ flexible substituents, such as octyl, shows formation of weak aggregates only, which do not contribute to reinforcement. The rubbery modulus of the networks with POSS in a junction grows with increasing POSS functionality due to enhanced network cross-link density. These networks are more homogeneous, and the modulus of the network with the octafunctional POSS junction well agrees with theoretical prediction. The mechanical properties are affected mainly by POSS−POSS interactions while the POSS-network chain interactions are of minor importance.

Nonlinear optical polyimides with various substituents on chromophores: synthesis and glass transition temperature

Abstract Glass transition temperature ( T g ) of nonlinear optical polyimide was observed with a variation of substituents on chromophore side chain. Several alkyls and functional groups were synthetically introduced on both electron accepting and donating groups of the chromophores. The polymers were thermally characterized with a differential scanning calorimetric analysis (DSC). The glass transition occurred at a range of 160–230 °C according to introducing substituents. An ester group in the chromophore tends to lower T g in the corresponding polyimide compared to a nitrile or a sulfone. Flexible and bulky substituents led to decrease T g of the polymer. Electro-optic coefficients were measured to compare nonlinear optical performance of similar polymers with different T g .