FimH antagonists: structure-activity and structure-property relationships for biphenyl α-D-mannopyranosides

Urinary tract infections (UTIs) are caused primarily by uropathogenic Escherichia coli (UPEC), which encode filamentous surface‐adhesive organelles called type 1 pili. FimH is located at the tips of these pili. The initial attachment of UPEC to host cells is mediated by the interaction of the carbohydrate recognition domain (CRD) of FimH with oligomannosides on urothelial cells. Blocking these lectins with carbohydrates or analogues thereof prevents bacterial adhesion to host cells and therefore offers a potential therapeutic approach for prevention and/or treatment of UTIs. Although numerous FimH antagonists have been developed so far, few of them meet the requirement for clinical application due to poor pharmacokinetics. Additionally, the binding mode of an antagonist to the CRD of FimH can switch from an in‐docking mode to an out‐docking mode, depending on the structure of the antagonist. In this communication, biphenyl α‐D ‐mannosides were modified to improve their binding affinity, to explore their binding mode, and to optimize their pharmacokinetic properties. The inhibitory potential of the FimH antagonists was measured in a cell‐free competitive binding assay, a cell‐based flow cytometry assay, and by isothermal titration calorimetry. Furthermore, pharmacokinetic properties such as log D, solubility, and membrane permeation were analyzed. As a result, a structure–activity and structure–property relationships were established for a series of biphenyl α‐D ‐mannosides.     

Antivirulence Isoquinolone Mannosides: Optimization of the Biaryl Aglycone for FimH Lectin Binding Affinity and Efficacy in the Treatment of Chronic UTI

Uropathogenic E. coli (UPEC) employ the mannose‐binding adhesin FimH to colonize the bladder epithelium during urinary tract infection (UTI). Previously reported FimH antagonists exhibit good potency and efficacy, but low bioavailability and a short half‐life in vivo. In a rational design strategy, we obtained an X‐ray structure of lead mannosides and then designed mannosides with improved drug‐like properties. We show that cyclizing the carboxamide onto the biphenyl B‐ring aglycone of biphenyl mannosides into a fused heterocyclic ring, generates new biaryl mannosides such as isoquinolone 22 (2‐methyl‐4‐(1‐oxo‐1,2‐dihydroisoquinolin‐7‐yl)phenyl α‐d ‐mannopyranoside) with enhanced potency and in vivo efficacy resulting from increased oral bioavailability. N‐Substitution of the isoquinolone aglycone with various functionalities produced a new potent subseries of FimH antagonists. All analogues of the subseries have higher FimH binding affinity than unsubstituted lead 22 , as determined by thermal shift differential scanning fluorimetry assay. Mannosides with pyridyl substitution on the isoquinolone group inhibit bacteria‐mediated hemagglutination and prevent biofilm formation by UPEC with single‐digit nanomolar potency, which is unprecedented for any FimH antagonists or any other antivirulence compounds reported to date.     

The Antiadhesive Strategy in Crohn′s Disease: Orally Active Mannosides to Decolonize Pathogenic Escherichia coli from the Gut

Blocking the adherence of bacteria to cells is an attractive complementary approach to current antibiotic treatments, which are faced with increasing resistance. This strategy has been particularly studied in the context of urinary tract infections (UTIs), in which the adhesion of pathogenic Escherichia coli strains to uroepithelial cells is prevented by blocking the FimH adhesin expressed at the tips of bacteria organelles called fimbriae. Recently, we extended the antiadhesive concept, showing that potent FimH antagonists can block the attachment of adherent‐invasive E. coli (AIEC) colonizing the intestinal mucosa of patients with Crohn′s disease (CD). In this work, we designed a small library of analogues of heptyl mannoside (HM), a previously identified nanomolar FimH inhibitor, but one that displays poor antiadhesive effects in vivo. The anomeric oxygen atom was replaced by a sulfur or a methylene group to prevent hydrolysis by intestinal glycosidases, and chemical groups were attached at the end of the alkyl tail. Importantly, a lead compound was shown to reduce AIEC levels in the feces and in the colonic and ileal mucosa after oral administration (10 mg kg^?1) in a transgenic mouse model of CD. The compound showed a low bioavailability, preferable in this instance, thus suggesting the possibility of setting up an innovative antiadhesive therapy, based on the water‐soluble and non‐cytotoxic FimH antagonists developed here, for the CD subpopulation in which AIEC plays a key role.     

Prediction of the creep of heterogeneous polymer blends: Rubber‐toughened polypropylene/poly(styrene‐co‐acrylonitrile)

A previously proposed predictive format for elastic, storage and loss moduli is extended for the time‐dependent compliance D_b(t) of polymer blends. The format employs a two‐parameter equivalent box model (EBM) and the data on the phase continuity of components in blends obtained by using modified general equations of the percolation theory. As input data, the compliances D₁(t) and D₂(t) and the critical volume fractions V_1cr and V_2cr (delimiting the interval of phase co‐continuity in blends) of components are sufficient. To describe the effect of time on D₁(t), D₂(t) and D_b(t) within the linear stress‐strain region, a routinely used empirical equation was found suitable. Applicability of the proposed format is demonstrated on rubbertoughened polypropylene/poly(styrene‐co‐acrylonitrile) blends consisting of components with markedly different viscoelastic properties. The proposed predictive format fits fairly well the creep behavior of blends over the interval 0.1‐10,000 minutes.     

The Tyrosine Gate of the Bacterial Lectin FimH: A Conformational Analysis by NMR Spectroscopy and X‐ray Crystallography

Urinary tract infections caused by uropathogenic E. coli are among the most prevalent infectious diseases. The mannose‐specific lectin FimH mediates the adhesion of the bacteria to the urothelium, thus enabling host cell invasion and recurrent infections. An attractive alternative to antibiotic treatment is the development of FimH antagonists that mimic the physiological ligand. A large variety of candidate drugs have been developed and characterized by means of in vitro studies and animal models. Here we present the X‐ray co‐crystal structures of FimH with members of four antagonist classes. In three of these cases no structural data had previously been available. We used NMR spectroscopy to characterize FimH–antagonist interactions further by chemical shift perturbation. The analysis allowed a clear determination of the conformation of the tyrosine gate motif that is crucial for the interaction with aglycone moieties and was not obvious from X‐ray structural data alone. Finally, ITC experiments provided insight into the thermodynamics of antagonist binding. In conjunction with the structural information from X‐ray and NMR experiments the results provide a mechanism for the often‐observed enthalpy–entropy compensation of FimH antagonists that plays a role in fine‐tuning of the interaction.     

Improvement of Aglycone π-Stacking Yields Nanomolar to Sub-nanomolar FimH Antagonists

Antimicrobial resistance has become a serious concern for the treatment of urinary tract infections. In this context, an anti-adhesive approach targeting FimH, a bacterial lectin enabling the attachment of E. coli to host cells, has attracted considerable interest. FimH can adopt a low/medium-affinity state in the absence and a high-affinity state in the presence of shear forces. Until recently, mostly the high-affinity state has been investigated, despite the fact that a therapeutic antagonist should bind predominantly to the low-affinity state. In this communication, we demonstrate that fluorination of biphenyl α-d -mannosides leads to compounds with perfect π–π stacking interactions with the tyrosine gate of FimH, yielding low nanomolar to sub-nanomolar K_D values for the low- and high-affinity states, respectively. The face-to-face alignment of the perfluorinated biphenyl group of FimH ligands and Tyr48 was confirmed by crystal structures as well as ¹H,¹⁵N-HSQC NMR analysis. Finally, fluorination improves pharmacokinetic parameters predictive for oral availability.     

Evaluation of (4‐Arylpiperidin‐1‐yl)cyclopentanecarboxamides As High‐Affinity and Long‐Residence‐Time Antagonists for the CCR2 Receptor

Animal models suggest that the chemokine ligand 2/CC‐chemokine receptor 2 (CCL2/CCR2) axis plays an important role in the development of inflammatory diseases. However, CCR2 antagonists have failed in clinical trials because of a lack of efficacy. We previously described a new approach for the design of CCR2 antagonists by the use of structure–kinetics relationships (SKRs). Herein we report new findings on the structure–affinity relationships (SARs) and SKRs of the reference compound MK‐0483, its diastereomers, and its structural analogues as CCR2 antagonists. The SARs of the 4‐arylpiperidine group suggest that lipophilic hydrogen‐bond‐accepting substituents at the 3‐position are favorable. However, the SKRs suggest that a lipophilic group with a certain size is desired [e.g., 3‐Br: K_i=2.8 nM , residence time (t_res)=243 min; 3‐iPr: K_i=3.6 nM , t_res=266 min]. Alternatively, additional substituents and further optimization of the molecule, while keeping a carboxylic acid at the 3‐position, can also prolong t_res; this was most prominently observed in MK‐0483 (K_i=1.2 nM , t_res=724 min) and a close analogue (K_i=7.8 nM ) with a short residence time.     

Kinetic study of the free‐radical polymerization of vinyl acetate in the presence of deuterated chloroform by 1H‐NMR spectroscopy

The free‐radical polymerization of vinyl acetate was performed in the presence of deuterated chloroform (CDCl₃) as a chain‐transfer agent (telogen) and 2,2′‐azobisisobutyronitrile as an initiator. The effects of the initiator and solvent concentrations (or equivalent monomer concentration) and the reaction temperature on the reaction kinetics were studied by real‐time ¹H‐NMR spectroscopy. Data obtained from analysis of the ¹H‐NMR spectra were used to calculate some kinetic parameters, such as the initiator decomposition rate constant (k_d), k_p(f/k_t)^1/2 ratio (where k_p is the average rate constant for propagation, f is the initiator efficiency, and k_t is the average rate constant for termination), and transfer constant to CDCl₃ (C). The results show that k_d and k_p(f/k_t)^1/2 changed significantly with the solvent concentration and reaction temperature, whereas they remained almost constant with the initiator concentration. C changed only with the reaction temperature. Attempts were made to explain the dependence of k_p(f/k_t)^1/2 on the solvent concentration. We concluded from the solvent‐independent C values that the solvent did not have any significant effect on the k_p values. As a result, changes in the k_p(f/k_t)^1/2 values with solvent concentration were attributed to the solvent effect on the f and/or k_t values. Individual values of f and k_t were estimated, and we observed that both the f and k_t values were dependent on the solvent (or equivalent monomer) concentration. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008     

Effective thermal conductivity and thermal properties of phthalonitrile‐terminated poly(arylene ether nitriles) composites with hybrid functionalized alumina

A polymer‐based thermal conductive composite has been developed. It is based on a dispersion of micro‐ and nanosized alumina (Al₂O₃) in the phthalonitrile‐terminated poly (arylene ether nitriles) (PEN‐t‐ph) via solution casting method. The Al₂O₃ with different particle sizes were functionalized with phthalocyanine (Pc) which was used as coupling agent to improve the compatibility of Al₂O₃ and PEN‐t‐ph matrix. The content of microsized functionalized Al₂O₃ (m‐f‐Al₂O₃) maintained at 30 wt % to form the main thermally conductive path in the composites, and the nanosized functionalized Al₂O₃ (n‐f‐Al₂O₃) act as connection role to provide additional channels for the heat flow. The thermal conductivity of the f‐Al₂O₃/PEN‐t‐ph composites were investigated as a function of n‐f‐Al₂O₃ loading. Also, a remarkable improvement of the thermal conductivity from 0.206 to 0.467 W/mK was achieved at 30 wt % n‐f‐Al₂O₃ loading, which is nearly 2.7‐fold higher than that of pure PEN‐t‐ph polymer. Furthermore, the mechanical testing reveals that the tensile strength increased from 99 MPa for pure PEN‐t‐ph to 105 MPa for composites with 30 wt % m‐f‐Al₂O₃ filler loading. In addition, the PEN‐t‐ph composites possess excellent thermal properties with glass transition temperature (T_g) above 184°C, and initial degradation temperature (T_id) over 490°C. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 41595.     

On the Use of Non‐Symmetrical Mixed PCN and SCN Pincer Palladacycles as Catalyst Precursors for the Heck Reaction

The mixed pincer palladacycles (Me₂NCH₂(Cl)CCCH₂CH₂Y‐κN,κC,κY)PdCl ( 1 , Y=PPh₂; 2 , OPPh₂) and (t‐BuSCH₂CH₂CC(Cl)(o‐NC₅H₄)‐κS,κC,κN)PdCl 3 have been obtained in high yields by chloropalladation of heterosusbstituted alkynes Me₂NCH₂CCCH₂CH₂PPh₂, Me₂NCH₂CCCH₂CH₂OPPh₂ and t‐BuSCH₂CH₂CC(o‐NC₅H₄), respectively. The molecular structures of 1 and 3 have been ascertained by means of X‐ray diffraction analysis. The catalytic properties of these mixed donor group pincer‐type palladacycles have been evaluated in the arylation of olefins (Heck reaction). The pincer palladacycle 1 is highly active for the coupling of aryl iodides and aryl bromides with n‐butyl acrylate. In contrast it is only moderately active for the coupling of aryl chlorides substituted with electron‐withdrawing groups and inactive for the coupling of electron neutral and electron deactivated aryl chlorides.     

Ethylene polymerisation by Ni–diphosphine azine complexes

The properties of [NiX(PR₂CH₂C(Bu^t)?NN?C(Bu^t)CH₂PR₂)]⁺ complexes (where X = Br, and R = cyclohexyl (Cy), isopropyl (Prⁱ), tert‐butyl (Bu^t), phenyl (Ph); X = Cl or I, and R = cyclohexyl) as catalysts for the polymerisation of ethylene were evaluated with or without the co‐catalysts methylaluminoxane (MAO), diethylaluminium chloride, trimethylaluminium or tri(isobutyl)aluminium. Their efficiency depends on the characteristics of the halogen (X) and the R group of the diphosphine azine ligand. Bromide (X) strongly enhances the catalytic properties of the complexes within the R order Cy > Prⁱ > Ph > Bu^t. Temperature, co‐catalyst ratio (Al/Ni) and complex concentration also influence the catalytic activity. The best results were obtained with [NiBr{PCy₂CH₂C(Bu^t)?NN?C(Bu^t)CH₂PCy₂}]Br activated by MAO (A = 25.8 kg (mol Ni)^?1 bar^?1 h^?1). The polymers were characterised using NMR and differential scanning calorimetry as branched polyethylenes, the number of branches increasing with the temperature of polymerisation. The molecular weights of the polymers were estimated using NMR. A proposal for the catalyst active precursor is made on the basis of experimental data and molecular orbital calculations. Copyright © 2007 Society of Chemical Industry     

Thermal stability and electric‐field‐induced strain behaviors for PIN‐PSN‐PT piezoelectric ceramics

Pb (In_1/2Nb_1/2) O₃‐Pb (Sc_1/2Nb_1/2) O₃‐PbTiO₃ (PIN‐PSN‐PT) ternary ceramics with compositions near morphotropic phase boundary (MPB) were fabricated by solid‐state‐sintering process. Dielectric and piezoelectric properties of xPIN‐yPSN‐zPT (x = 0.19, 0.23 and z = 0.365, 0.385) ceramics were investigated as a function of temperature, showing high T_r‐t and T_c on the order of 160 ~ 200°C and 280 ~ 290°C, respectively. The xPIN‐yPSN‐0.365PT (x = 0.19 and 0.23) ceramics do not depolarize at the temperature up to 200°C, showing a better thermal stability when compared to the state‐of‐the‐art relaxor‐PbTiO₃ systems. A slight variation (<9%) of k_p, k_t, and k₃₃ was observed in the temperature range of 25°C‐160°C for xPIN‐yPSN‐0.385PT (x = 0.19 and 0.23) ceramics. Rayleigh analysis was employed to quantify the contribution of domain wall motion to piezoelectric response, where the domain wall contribution was found to increase with composition approaching MPB for PIN‐PSN‐PT system.     

NMR properties of poly(dimethyl siloxane) colloids as new contrast agents for NMR imaging

By connecting the field‐gradient spin‐echo theory to spin–spin relaxation, we have found that the relationship between the tube‐reptation model and spin–spin relaxation can be represented by G(t) = exp[−(t/T₂) ⁿ] in which n = 1 and 0.5 for regimes IV and III, respectively. In our experiments, the spin–spin relaxation of linear poly(dimethyl siloxane) (PDMS) agrees with G(t) = exp[−(t/T₂)] while that of crosslinked PDMS coincides with G(t) = exp[−(t/T₂)^0.5]. These results reflect that in the time interval 8–800 ms the dynamics of linear PDMS are in regime IV (governed by reptation motions) and those of the crosslinked PDMS are in regime III (dominated by wriggling motions). The line‐shapes of NMR spectra of crosslinked PDMS are consistent with the Lorentzian rather than the Gaussian model. This can be accounted for by supposing that the PDMS chains between crosslinks have liquid‐like motions even though crosslinked PDMS is a solid. The liquid‐like motions of crosslinked PDMS could be regarded as wriggling motions described by the tube‐reptation model. In addition, the experimental results of diameter distribution, viscosity, NMR image and spin–lattice relaxation are presented in this work. © 2000 Society of Chemical Industry     

Correlation between migration behaviors of antiozonants and temperature

Migration behaviors of antiozonants depending on temperature were studied using a carbon black‐filled NR vulcanizate containing N‐phenyl‐N′‐isopropyl‐p‐phenylenediamine (IPPD) and N‐phenyl‐N′‐(1,3‐dimethylbutyl)‐p‐phenylenediamine (HPPD) as antiozonants. The experimental temperatures were 100, 90, 80, and 70°C. Migration rates of them increased steeply by increasing the temperature. The correlation between the migration rates and the temperature was investigated using the half (t_1/2)‐ and quarter (t_1/4)‐lifetimes of the migrants remaining in the vulcanizate after the migration. The plot of log t versus 1/T was well fitted by the linear equation: The correlation coefficients were higher than 0.995. It was found that the migration behavior and temperature had a correlation of log t = b/T + c, where t and T are the migration time and temperature, b is E_a/R, and c is the constant. The activation energies for the migration were 36.48 and 37.93 kJ/mol for IPPD and HPPD, respectively. © 2001 John Wiley & Sons, Inc. J Appl Polym Sci 80: 1566–1570, 2001     

Block copolymerizations of higher 1‐olefins with traditional polar monomers using metallocene‐type single component lanthanide initiators

Block copolymerizations of 1‐pentene or 1‐hexene with methyl methacrylate or ε‐caprolactone were explored using [Me₂Si(2‐SiMe₃‐4‐t‐BuMe₂SiC₅H₂)₂YH]₂ ( 1 ) or [Me₂Si(2‐SiMe₃‐4‐t‐BuC₅H₂)₂SmH]₂ ( 2 ) as an initiator in toluene or in neat mixtures by the successive additions of monomers in this order. Random copolymerizations of 1‐pentene with 1‐hexene, and random copolymerization of ethylene with 1‐hexene were also performed using 1 as an initiator. Copyright © 2004 Society of Chemical Industry     

Optimization and effect of 3‐aminopropyltriethoxysilane content on the properties of bentonite‐filled ethylene propylene diene monomer composites

The effect of silane coupling agent, 3‐aminopropyltriethoxysilane (APTES) content on the curing, tensile, swelling, and morphological properties of bentonite (Bt)‐filled ethylene‐propylene‐diene monomer (EPDM) composite was studied. The EPDM composites containing constant Bt composition of 30 phr and various APTES content (0, 1, 3, and 5 phr) were prepared using a laboratory scale two‐roll mill. The result showed that the cure time (t₉₀) and scorch time (t_S2) were shortened, whilst, the cure rate index (CRI), the maximum (M_H) and minimum (M_L) torque increased with increasing APTES content. The experimental results revealed that the optimum APTES content that led to the highest tensile and swelling properties was 3 phr. The presence of APTES greatly improved the dispersion of Bt in EPDM matrix and enhanced the interfacial interaction between EPDM and Bt. Morphological study through scanning electron microscopy revealed the enhanced adhesion between EPDM and Bt in the presence of 3 phr APTES. POLYM. COMPOS., 33:1993–2000, 2012. © 2012 Society of Plastics Engineers     

High permittivity (1−x)Bi1/2Na1/2TiO3‐xPbMg1/3Nb2/3O3 ceramics for high‐temperature‐stable capacitors

(1?x)Bi_1/2Na_1/2TiO₃‐xPbMg_1/3Nb_2/3O₃[(1?x)BNT‐xPMN] ceramics have been fabricated via a conventional solid‐state method for compositions x ≤ 0.3. The microstructure, phase structure, ferroelectric, and dielectric properties of ceramics were systematically studied as high‐temperature capacitor materials. XRD pattern certified perovskite phase with no secondary phase in all compositions. As PMN concentration increased, the phase of (1?x)BNT‐xPMN ceramics transformed from ferroelectric to relaxor gradually at room temperature, with prominent enhancement of dielectric temperature stability. For the composition x = 0.2, the temperature coefficient of capacitance (TCC) was <15% in a wide temperature range from 56 to 350°C with high relative permittivity (>3300) and low dielectric loss (<0.02) at 150°C, which indicated promising future for (1?x)BNT‐xPMN system as high‐temperature stable capacitor materials.     

Synthesis,antimicrobial, and release behaviors of tetracycline hydrochloride loaded poly (VInyl alcohol)/chitosan/ZrO2 nanofibers

Tetracycline hydrochloride loaded poly (vinyl alcohol)/chitosan/ZrO₂ (Tet‐PVA/CS/ZrO₂) hybrid nanofibers were fabricated via electrospinning technique. The representative weight ratio of PVA/CS at 3 : 1 was chosen to fabricate drug carrier PVA/CS/ZrO₂ nanofibers. The drug carrier showed a decrease in average diameter with the increase of ZrO₂ content at given conditions, and the nanofibers were uneven and interspersed with spindle‐shape beads with ZrO₂ content at 60 wt % and above. The networks linked by hydrogen and Zr–O–C bonds among PVA, CS, and ZrO₂ units resulted in the improving of thermal stability and decreasing of crystallinity of the polymeric matrix. Moreover, the incorporation of ZrO₂ endowed the fibers with ultraviolet shielding effect ranged from 200 to 400 nm. The Tet loading dosage had no obvious effect on the morphology and size of the medicated nanofibers at Tet content below 8 wt %, but interspersed with spindle‐shaped beads when Tet content increased to 10 wt %. The Tet‐PVA/CS/ZrO₂) nanofibers showed well controlled release and better antimicrobial activity against Staphylococcus aureus, and the Tet release from the medicated nanofibers could be described by Fickian diffusion model for M_t /M_∞< 0.6. These medicated nanofibers may have potential as a suitable material in drug delivery and wound dressing. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 42506.     

Insect sex pheromones: Evaporation rates of alcohols and acetates from natural rubber septa

The half-lives (t _1/2) of alcohol sex pheromones, 1-alkanols, acetate sex pheromones, and an epoxide (disparlure) were determined on natural rubber septa. Thet _1/2 values for the homologous alcohols from decanol to heptadecanol increased regularly from 2.2 to 1117 days, but thet _1/2 of octadecanol was 609 days. Thet _1/2 values of (Z)7-, (E)7-, and (Z)9-tetradecen-1-ol acetates were 154, 168, and 199 days, respectively, whereas those of five other tested 14-carbon acetates ranged from 310 to 350 days. The dependence oft _1/2 values on chain length and double-bond position is consistent with the hypothesis that molecular size is an important variable affectingt _1/2 values. Also, in accordance with the hypothesis, when aZ-alkenyl compound has a much shortert _1/2 than the corresponding saturated compound, thet _1/2 values of theZ compound and itsE isomer may be quite different. Thus, (E)-9-tetradecen-l-ol acetate had at _1/2 of 331 days. Thet _1/2 of disparlure was 180 days. The effect of thecis-7,8 epoxide group is apparently similar to that of the olefin group in lowering thet _1/2 below the value that would be expected solely on the basis of chain length.This paper reports the results of research only. Mention of a commercial product in this paper does not constitute a recommendation by the U.S. Department of Agriculture.     

Ethylene/1‐octadecene copolymerization using [η5:η1‐C5Me4‐4‐R1‐6‐R‐C6H2O]TiCl2 catalysts

Copolymerization of ethylene with 1‐octadecene was studied using [η⁵:η¹‐C₅Me₄‐4‐R₁‐6‐R‐C₆H₂O]TiCl₂ [R₁ = ^tBu (1), H (2, 3, 4); R = ^tBu (1, 2), Me (3), Ph (4)] as catalysts in the presence of Al(i‐Bu)₃ and [Ph₃C][B(C₆F₅)₄]. The effect of the concentration of comonomer in the feed and Al/Ti molar ratio on the catalytic activity and molecular weight of the resultant copolymer were investigated. The substituents on the phenyl ring of the ligand affect considerably both the catalytic activity and comonomer incorporation. The 1 /Al(i‐Bu)₃/[Ph₃C][B(C₆F₅)₄] catalyst system exhibits the highest catalytic activity and produces copolymers with the highest molecular weight, while the 2 /Al(i‐Bu)₃/[Ph₃C][B(C₆F₅)₄] catalyst system gives copolymers with the highest comonomer incorporation under similar conditions. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2011