bluuebunny/crossref_metadata_2025_split huggingface dataset:
KHCO3‐ and DBU‐Promoted Cascade Reaction to Synthesize 3‐Benzyl‐2‐phenylquinolin‐4(1 H)‐ones
Authors: Ma Haojie , Zhou Xiaoqiang , Wei DaiDong , Cao Jinhui , Shi Chong , Fan Yuxing , Huang Guosheng 
Published: September 2016

AbstractA novel and convenient one‐pot route for the synthesis of 3‐benzyl‐2‐phenylquinolin‐4(1 H)‐ones has been developed under transition‐metal‐free conditions. This new strategy features high yield and good functional group tolerance. In addition, a proposed mechanism has been confirmed for this reaction.
Extreme makeover: Engineering the activity of a thermostable alcohol dehydrogenase (AdhD) from Pyrococcus furiosus
Authors: Solanki Kusum , Abdallah Walaa , Banta Scott 
Published: September 2016

AbstractAlcohol dehydrogenase D (AdhD) is a monomeric thermostable alcohol dehydrogenase from the aldo‐keto reductase (AKR) superfamily of proteins. We have been exploring various strategies of engineering the activity of AdhD so that it could be employed in future biotechnology applications. Driven by insights made in other AKRs, we have made mutations in the cofactor‐binding pocket of the enzyme and broadened its cofactor specificity. A pre‐steady state kinetic analysis yielded new insights into the conformational behavior of this enzyme. The most active mutant enzyme concomitantly gained activity with a non‐native cofactor, nicotinamide mononucleotide, NMN(H), and an enzymatic biofuel cell was demonstrated with this enzyme/cofactor pair. Substrate specificity was altered by grafting loop regions near the active site pocket from a mesostable human aldose reductase (hAR) onto the thermostable AdhD. These moves not only transferred the substrate specificity of hAR but also the cofactor specificity of hAR. We have added alpha‐helical appendages to AdhD to enable it to self‐assemble into a thermostable catalytic proteinaceous hydrogel. As our understanding of the structure/function relationship in AdhD and other AKRs advances, this ubiquitous protein scaffold could be engineered for a variety of catalytic activities that will be useful for many future applications.
Luminescence and Magnetic Properties of Tb(III) Complexes with TETA and Synergistic Effect by 1,10‐Phenanthroline
Authors: Kang Jung‐Soo , Leung Kam Tong , Cho Hyung‐Kook , Kang Jun‐Gill , Sohn Youngku 
Published: September 2016

Two Tb(III) complexes, [Tb(TETA)]− and [Tb(TETA)(phen)]− (TETA = 1,4,8,11‐tetraazacyclotetradecane‐1,4,8,11‐tetraacetate and phen = 1,10‐phenanthroline), were synthesized and their luminescence (
5D4
→
7F
J

=0–6 transitions) and magnetic properties were examined. The photoluminescence (PL) quantum yield of [Tb(TETA)(phen)]− (Q = 0.47) was significantly higher than that of [Tb(TETA)]− (Q = 0.006). The dramatic increase (78×) in green luminescence was attributed to intramolecular energy transfer from phen to Tb(III). The energy transfer rate according to Dexter theory was found to be approximately 1011 s−1. The temperature dependence of the molar susceptibilities confirmed that the two complexes behave as paramagnets obeying the Curie–Weiss law. In addition, the field‐dependent magnetization of the two complexes measured in the −70 to + 70 kOe range at T = 1.8 K fitted well with the Brillouin function with the following values: g
eff = 1.5, μ

B
= 9.27 × 10−21 emu, and J = 6. These results provide new insights into the development of lanthanide metal complexes with tetraaza © 2016 Korean Chemical Society, Seoul & Wiley‐VCH Verlag GmbH & Co. KGaA, Weinheimmacrocyclic ligands.
Absolute oral bioavailability of fenofibric acid and choline fenofibrate in rats determined by ultra‐performance liquid chromatography tandem mass spectrometry
Authors: Wei Xudan , Li Ping , Liu Meina , Du Yuqian , Wang Menglin , Zhang Jinling , Wang Jing , Liu Hongzhuo , Liu Xiaohong 
Published: September 2016

AbstractCholine fenofibrate is the choline salt of fenofibric acid, which releases free fenofibric acid in the gastrointestinal tract. To estimate the absolute oral bioavailability of fenofibric acid and choline fenofibrate, a novel and sensitive UPLC–MS/MS method with liquid–liquid extraction procedure was developed for the determination of fenofibric acid in rat plasma. The separation was achieved on a Phenomenex Kinetex C18 column (50 × 2.1 mm, 2.6 μm) containing 2 mm ammonium acetate–methanol with a gradient elution program. Validations of this method including specificity, sensitivity (limit of quantification, 5 ng/mL), linearity (0.005–10 μg/mL), accuracy (within ±4.3%), precision (intra‐ and inter‐day coefficient of variation <11.3%), recovery (94.9–105.2% for fenofibric acid), matrix effect, stability and dilution, were all within acceptable limits. This method successfully supported the determination of fenofibric acid and choline fenofibrate. The absolute oral bioavailability was 93.4% for choline fenofibrate and 40.0% for fenofibric acid. These results suggested that choline fenofibrate and fenofibric acid had a better in vivo pharmacokinetic behavior than that of fenofibrate. The two new orally administrated pharmaceuticals, fenofibric acid and choline fenofibrate, can be developed as alternatives to fenofibrate.
Chemical Composition and Antimicrobial Activity of Satureja, Thymus, and Thymbra Species Grown in Lebanon
Authors: Al Hafi Monay , El Beyrouthy Marc , Ouaini Naim , Stien Didier , Rutledge Douglas , Chaillou Sylvain 
Published: September 2016

The essential oils were extracted by hydrodistillation from Satureja cuneifolia, Satureja thymbra, Coridothymus capitatus, Thymus syriacus, and Thymbra spicata growing wild in Lebanon. Their phytochemical analysis performed by GC/MS showed that the aforementioned species are characterized either by carvacrol (60.9%) or thymol (54.3%) or by a more or less equal amounts of these two phenols. Assessment of their in vitro antimicrobial activity against Candida albicans and six pathogenic bacteria using the broth dilution method revealed that the tested oils have a broad activity spectrum with minimum inhibitory concentration ranging from 0.1 to 0.8 mg/ml. Among the tested species, S. thymbra EO showed the highest antimicrobial potential whereas T. syriacus showed the lowest inhibitory activity. These results give scientific evidence for the use of those species in the Lebanese folk medicine and lend support to implement them as natural alternatives for synthetic antimicrobials.
The Physical Properties and Self‐Assembly Potential of the RFFFR Peptide
Authors: Slyngborg Morten , Nielsen Dennis Achton , Fojan Peter 
Published: September 2016

AbstractThe self‐assembly of fibers from peptides has attracted a tremendous amount of attention due to its many applications, such as in drug‐delivery systems, in tissue engineering, and in electronic devices. Recently, the self‐assembly potential of the designer peptide RFFFR has been reported. Here it is experimentally verified that the peptide forms fibers that are entangled and form solid spheres without water inside. Upon dilution below the critical fiber concentration, the fibers untangle and become totally separated prior to dissolution. These structures readily bind thioflavin T, resulting in a characteristic change in fluorescent properties consistent with β‐sheet‐rich amyloid structures with aromatic/hydrophobic grooves. The circular dichroism spectroscopy data are dominated by a π→π* transition, thus indicating that the fibers are stabilized by π‐stacking. Contrary to what was expected, the dissolution of the spheres/fibers results in increasing fluorescence anisotropy over time. This is explained in terms of HomoFRET between phenylalanine residues with a T‐shaped π‐stacking mode, which was determined in another study to be the dominant mode through atomistic simulations and semiempirical calculations. Kelvin probe force microscopy measurements indicate that the spheres and fibers have a conductivity comparable to that of gold. Hence, these self‐assembled structures might be applicable in organic solid‐state electronic devices. The dissolution properties of the spheres further suggest that they might be used as drug‐delivery systems.
The fast track to canonical Wnt signaling in MC3T3‐E1 cells protected by substance P against serum deprivation‐induced apoptosis
Authors: Yang Jianguo , Nie Jiping , Fu Su , Liu Song , Wu Jianqun , Cui Liang , Zhang Yongtao , Yu Bin 
Published: September 2016

AbstractThe canonical Wnt pathway is vital to bone physiology by increasing bone mass through elevated osteoblast survival. Although investigated extensively in stem cells, its role in osteoblastic MC3T3‐E1 cells has not been completely determined. To explore how this pathway is regulated by different conditions, we assessed the anti‐apoptotic effects of substance P on the canonical Wnt pathway in MC3T3‐E1 cells by treating cells with serum deprivation or serum starving with “substance P,” a neuropeptide demonstrated to promote bone growth and stimulate Wnt signaling. The results showed that serum deprivation both induced apoptosis and activated Wnt signal transduction while substance P further stimulated the Wnt pathway via the NK‐1 receptor but protected the cells from apoptotic death. Fast‐tracking of Wnt signaling by substance P was also noted. These results indicate that nutritional deprivation and substance P synergistically activated the canonical Wnt pathway, a finding that helps to reveal the role of Wnt signaling in bone physiology affected by nutritional deprivation and neuropeptide substance P.
Asymptomatic parental mosaicism for osteogenesis imperfecta associated with a new splice site mutation in COL1A2
Authors: Frederiksen Anja Lisbeth , Duno Morten , Johnsen Iben B. G. , Nielsen Morten Frost , Krøigård Anne Bruun 
Published: September 2016

Key Clinical MessageRecurrent lethal perinatal osteogenesis imperfecta may result from asymptomatic parental mosaicism. A previously unreported mutation in COL1A2 leads to recurrent cases of fetal osteogenesis imperfecta Sillence type IIA, which emphasizes the importance of clinical and genetic evaluation of mosaicism in asymptomatic parents as verified mosaicism highly increases recurrence risk.
Palladium Nanoparticles Hosted on Hydrazine‐Grafted Magnetite and Silica Particles to Catalyze the Reduction of Oxymetal Ions with Formic Acid
Authors: Shrivastava Komal C. , Chappa Sankararao , Sengupta Arijit , Srivastava Amit P. , Pandey Ashok K. , Ramakumar Karanam L. 
Published: September 2016

AbstractA new synthetic route has been developed to anchor a large amount of Pd nanoparticles (NPs) on the surface of hydrazine‐grafted and (3‐glycidyloxypropyl)trimethoxysilane‐coated inorganic host particles such as Fe3O4 and SiO2. The hydrazine‐grafted inorganic particles reduce Pd2+ ions spontaneously under ambient conditions. This results in the production of Pd0 seeds and their nucleation, which leads to the growth of Pd NPs on the surface of the host particle itself. These anchored Pd NPs on Fe3O4 and SiO2 have been characterized by elemental analysis, microscopy, and elemental mapping. Spherical Pd NPs of ≈0.3 and 1 nm are formed uniformly on Fe3O4 (25 nm) and SiO2 (100 nm) particles, respectively. Their concentration on the host particles was 12 mg g−1 for Fe3O4 and 20 mg g−1 for SiO2. These host particles loaded with Pd NPs have been investigated for their catalytic activity in the reduction of representative oxymetal ions such as UO22+ and Cr2O72− ions with formic acid. NP‐loaded SiO2 exhibited a good catalytic activity in both these reductions, whereas Pd NPs on Fe3O4 could reduce Cr2O72− ions only.
Platinum Iron Intermetallic Nanoparticles Supported on Carbon Formed In Situ by High‐Pressure Pyrolysis for Efficient Oxygen Reduction
Authors: Hu Yang , Jensen Jens Oluf , Zhang Wei , Cleemann Lars N. , Pan Chao , Li Qingfeng 
Published: September 2016

AbstractCarbon‐supported PtFe alloy catalysts are synthesized by the one‐step, high‐temperature pyrolysis of Pt, Fe, and C precursors. As a result of the high temperature, the formed PtFe nanoparticles possess highly ordered, face‐centered tetragonal, intermetallic structures with a mean size of ≈11.8 nm. At 0.9 V versus the reversible hydrogen electrode, the PtFe nanoparticles show a 6.8 times higher specific activity than the reference Pt/C catalyst towards the oxygen reduction reaction (ORR) as well as excellent stability, most likely because of the durable intermetallic structure and the preleaching treatment of the catalyst. During these preliminary syntheses, we found that a portion of the PtFe nanoparticles is buried in the in situ formed carbon phase, which limits Pt utilization in the catalyst and results in a mass‐specific activity equivalent to the commercial Pt/C catalyst. Moreover, the possible presence of other active sites, for example, FeNx, CNx, and carbon‐encapsulated metal nanoparticles, and their contribution to the ORR performance of the catalyst are also investigated.
Long Alkyl Chain NHC Palladium Complexes for the Amination and Hydrodehalogenation of Aryl Chlorides in Lipophilic Media
Authors: Rühling Andreas , Rakers Lena , Glorius Frank 
Published: September 2016

AbstractHerein, we present the synthesis of long chain NHC palladium complexes, which are soluble in lipophilic solvents, such as n‐heptane. These complexes enable the amination and hydrodehalogenation of aryl chlorides in moderate to good yields for a broad range of substrates in n‐heptane. Taking into account the caloric power of alkane solvents, such transformations could become a welcome alternative to established solvents (e.g. dioxane) from an industrial point of view.
Tailoring Large Pores of Porphyrin Networks on Ag(111) by Metal–Organic Coordination
Authors: Bischoff Felix , He Yuanqin , Seufert Knud , Stassen Daphné , Bonifazi Davide , Barth Johannes V. , Auwärter Willi 
Published: September 2016

AbstractThe engineering of nanoarchitectures to achieve tailored properties relevant for macroscopic devices is a key motivation of organometallic surface science. To this end, understanding the role of molecular functionalities in structure formation and adatom coordination is of great importance. In this study, the differences in formation of Cu‐mediated metal–organic coordination networks based on two pyridyl‐ and cyano‐bearing free‐base porphyrins on Ag(111) are elucidated by use of low‐temperature scanning tunneling microscopy (STM). Distinct coordination networks evolve via different pathways upon codeposition of Cu adatoms. The cyano‐terminated module directly forms 2D porous networks featuring fourfold‐coordinated Cu nodes. By contrast, the pyridyl species engage in twofold coordination with Cu and a fully reticulated 2D network featuring a pore size exceeding 3 nm2 only evolves via an intermediate structure based on 1D coordination chains. The STM data and complementary Monte Carlo simulations reveal that these distinct network architectures originate from spatial constraints at the coordination centers. Cu adatoms are also shown to form two‐ and fourfold monoatomic coordination nodes with monotopic nitrogen‐terminated linkers on the very same metal substrate—a versatility that is not achieved by other 3d transition metal centers but consistent with 3D coordination chemistry. This study discloses how specific molecular functionalities can be applied to tailor coordination architectures and highlights the potential of Cu as coordination center in such low‐dimensional structures on surfaces.
Kinetically Controlled Assembly of Nitrogen‐Doped Invaginated Carbon Nanospheres with Tunable Mesopores
Authors: Liu Yang , Zhang Hongwei , Noonan Owen , Xu Chun , Niu Yuting , Yang Yannan , Zhou Liang , Huang Xiaodan , Yu Chengzhong 
Published: September 2016

AbstractMesoporous hollow carbon nanospheres (MHCS) have been extensively studied owning to their unique structural features and diverse potential applications. A surfactant‐free self‐assembly approach between resorcinol/formaldehyde and silicon alkoxide has emerged as an important strategy to prepare MHCS. Extending such a strategy to other substituted phenols to produce heterogeneous‐atom‐doped MHCS remains a challenge due to the very different polymerization kinetics of various resins. Herein, we report an ethylenediamine‐assisted strategy to control the cooperative self‐assembly between a 3‐aminophenol/formaldehyde resin and silica templates. Nitrogen‐doped mesoporous invaginated carbon nanospheres (N‐MICS) with an N content of 6.18 at %, high specific surface areas (up to 1118 m2 g−1), large pore volumes (2.47 cm3 g−1), and tunable mesopores (3.7–11.1 nm) have been prepared. When used as electrical double‐layer supercapacitors, N‐MICS show a high capacitance of 261 F g−1, an outstanding cycling stability (≈94 % capacitance retention after 10 000 cycles), and a good rate performance.
Synthesis of 2,3‐Disubstituted Quinolines via Ketenimine or Carbodiimide Intermediates
Authors: Zhao Hongyang , Xing Yanpeng , Lu Ping , Wang Yanguang 
Published: September 2016

AbstractCyclopenta[b]quinolines and cyclohexa[b]quinolines were prepared via the reactions of α‐diazo ketones with N‐(2‐cyclopropylidenemethylphenyl)phosphanimines and N‐(2‐cyclobutylidenemethylphenyl) phosphanimine, respectively. The reaction proceeds in a cascade involving ketenimine formation, 6 π‐electron ring closure, and 1,3‐alkyl shift. A similar approach was developed for the synthesis of dihydropyrrolo‐[2,3‐b]quinolines from N‐(2‐cyclopropylidenemethylphenyl)phosphanimines and isocyanates.
MnFe2O4 Nanocrystals Wrapped in a Porous Organic Polymer: A Designed Architecture for Water‐Splitting Photocatalysis
Authors: Dhanalaxmi Karnekanti , Yadav Rajkumar , Kundu Sudipta K. , Reddy Benjaram Mahipal , Amoli Vipin , Sinha Anil Kumar , Mondal John 
Published: September 2016

AbstractA novel MnFe2O4–porous organic polymer (POP) nanocomposite was synthesized by a facile hydrothermal method and using the highly cross‐linked N‐rich benzene–benzylamine POP. The nanocomposite presented highly efficient photocatalytic performance in the hydrogen evolution reaction (HER) from pure water without addition of any sacrificial agent under one AM 1.5 G sunlight illumination. A photocatalytic activity of 6.12 mmol h−1 g−1 was achieved in the absence of any noble metal cocatalyst, which is the highest H2 production rate reported for nonprecious metal catalysts. The photocatalytic performance of MnFe2O4‐POP could be attributed to the intrinsic synergistic effects of manganese ferrite (MnFe2O4) nanoclusters interacting with the nitrogen dopant POP with a unique mesoporous nanoarchitecture and spatially confined growth of MnFe2O4 in the interconnected POP network, leading to high visible‐light absorption with fast electron transport.
Unlocking Mizoroki–Heck‐Type Reactions of Aryl Cyanides Using Transfer Hydrocyanation as a Turnover‐Enabling Step
Authors: Fang Xianjie , Yu Peng , Prina Cerai Gabriele , Morandi Bill 
Published: September 2016

AbstractA new transfer hydrofunctionalization strategy to turnover H‐MII‐X complexes has enabled both intra‐ and intermolecular Mizoroki–Heck (MH)‐type reactions of aryl cyanides that are challenging to realize under traditional, basic conditions. Initially, a cascade carbonickelation/MH reaction of 2‐cyanostyrenes was achieved using a key alkyne transfer hydrocyanation step. Mechanistic experiments supported the proposed catalytic cycle, including the turnover‐enabling transfer hydrocyanation step. The reactivity was then extended to the intermolecular MH reaction of benzonitriles and styrenes.
ChemInform Abstract: Syntheses, Structures and Properties of Two New 3‐D Vanadoborates Based on V—O—B Clusters.
Authors: Tang Qiuling , Zhou Jian , Zou Hua‐Hong , Tan Xiao‐Feng 
Published: September 2016

Abstract(H3O)4{ [Cd(H2O)2] 3V12B18O54 (OH)6}·26H2O (I) and [K6 (H2O) 10Zn4V10B32O74 (OH)10]·5H2O (II) are prepared by hydrothermal reaction of a 0.7:9.9:0.2 molar mixture of V(acac)3, H3BO3, and Cd(O‐Ac)2 respectively a 0.7:10:0.25:2 molar mixture of NH4VO3, H3BO3, Zn(O‐Ac)2, and K2SO3 (aq.
ChemInform Abstract: On the Extended Series of Quaternary Zintl Phases Ca13REMnSb11 (RE: La—Nd, Sm, Gd—Dy).
Authors: Prakash Jai , Stoyko Stanislav , Voss Leonard , Bobev Svilen 
Published: September 2016

AbstractSingle crystalline Ca14‐xLnxMnSb11 (Ln: La—Nd, Sm, Gd—Dy; x ≈ 1) is prepared from the elements in a molten Pb flux with a 20% Ln and a 50—70% Mn excess (Al2O3 crucible in evacuated silica tubes, 1000 °C, 24 h).
ChemInform Abstract: Ionothermal Synthesis and Magnetic Study of a New Manganese(II) Phosphite with an unprecedented Mn/P Ratio.
Authors: Su Tan , Xing Hongzhu , Li Yi , Wu Junbiao , Song Xiaowei , Nakano Takehito , Yu Jihong 
Published: September 2016

AbstractThe layered Mn(II) phosphite (NH4)4[Mn4(PO3H)6] is prepared by ionothermal reaction of MnCl2·4H2O, H3PO3, and NH4F using 1‐pentyl‐3‐methylimidazolium bromide ([pmim]Br) as the solvent (autoclave, 150 °C, 7 d, ≈70% yield).
ChemInform Abstract: Tellurium‐Assisted Epitaxial Growth of Large‐Area, Highly Crystalline ReS2 Atomic Layers on Mica Substrate.
Authors: Xu Hua , et al.  
Published: September 2016

AbstractAnisotropic ReS2 monolayers with high crystallinity and uniform thickness are epitaxially grown in a tubular furnace equipped with a quartz tube containing S at the outside edge of the hot zone (≈200 °C) and a 1:6 wt.
ChemInform Abstract: Palladium‐Catalyzed Directing Group‐Assisted C8‐Triflation of Naphthalenes.
Authors: Yang Zhi‐Wei , Zhang Qi , Jiang Yuan‐Ye , Li Lei , Xiao Bin , Fu Yao 
Published: September 2016

AbstractThe first Pd‐catalyzed C‐H activation/C‐OTf bond forming process is developed to provide C8 triflated 1‐naphthylamides regioselectively.
ChemInform Abstract: Bifunctional AgOAc/ThioClickFerrophos Catalyzed Asymmetric 1,3‐Dipolar Cycloaddition Reaction of Azomethine Ylides to Nitroalkenes
Authors: Kimura Midori , Matsuda Yukiko , Koizumi Akihiro , Tokumitsu Chihiro , Tokoro Yuichiro , Fukuzawa Shin‐ichi 
Published: September 2016

Abstract18 examples
ChemInform Abstract: Enantioselective, Stereodivergent Hydroazidation and Hydroamination of Allenes Catalyzed by Acyclic Diaminocarbene (ADC) Gold(I) Complexes.
Authors: Khrakovsky Dimitri A. , Tao Chuanzhou , Johnson Miles W. , Thornbury Richard T. , Shevick Sophia L. , Toste F. Dean 
Published: September 2016

AbstractThe presented transformation is one of the rare examples where the product configuration depends on the nucleophile.
ChemInform Abstract: Divergent Copper‐Mediated Dimerization and Hydroxylation of Benzamides Involving C—H Bond Functionalization.
Authors: Wang Mingliang , Hu Yimin , Jiang Zhe , Shen Hong C. , Sun Xun 
Published: September 2016

AbstractConditions for either dimerization or 2‐hydroxylation of variously functionalized benzamides are elaborated.
ChemInform Abstract: Iodine‐Catalyzed Oxidative Functionalization of Azaarenes with Benzylic C(sp3)—H Bonds via N‐Alkylation/Amidation Cascade: Two‐Step Synthesis of Isoindolo[2,1‐b]isoquinolin‐7(5H)‐one.
Authors: Luo Wen‐Kun , Shi Xin , Zhou Wang , Yang Luo 
Published: September 2016

AbstractAn efficient metal‐free N‐benzylation of isoquinolines as well as quinoline, quinazoline and phthalazine with methylarenes is described.
ChemInform Abstract: Unexpected Formation of 4,4‐Dimethyl‐1,2‐disubstituted‐dicarbonyl Cyclopentanes from Ketone Enolate Anions and 1,3‐Diiodo‐2,2‐dimethylpropane.
Authors: Barrionuevo Cecilia A. , Schmidt Luciana C. , Argueello Juan E. 
Published: September 2016

AbstractUsing simple tert‐butoxide as base, the relatively complex five‐membered ring diketone structure of the title compounds is easily obtained under transition‐metal‐free conditions.
ChemInform Abstract: Cobalt‐Catalyzed Dehydrogenative Coupling of Alcohols/Aldehydes and Amines: An Important Role for Imine Hydration.
Authors: Guo Ya‐Fei , Ren Tian‐Lu , Xu Bao‐Hua , Wang Yao‐Feng , Zhang Suo‐Jiang 
Published: September 2016

AbstractA cobalt and iodide co‐catalyzed oxidative amidation reaction between alcohols or aldehydes and amines smoothly proceeds under mild conditions affording amides with broad functional group tolerance.