Recent Chemical Approaches for Site-Specific Conjugation of Native Antibodies: Technologies toward Next-Generation Antibody–Drug Conjugates

Antibody–drug conjugates (ADCs), which consist of three components, antibody, linker, and payload, can function as “magic bullets”. These conjugates offer the ability to target drug delivery to specific cells, based on cell-specific recognition and the binding of an antigen by a monoclonal antibody (mAb). In particular, by delivering a cytotoxic payload to cancer cells, ADCs are expected to provide a breakthrough in oncology treatments by providing a way to increase efficacy and decrease toxicity, in comparison with traditional chemotherapeutic treatments. The development of ADC therapeutics has dramatically progressed in the past decade and two ADCs have been approved and used as anticancer drugs in the clinic. However, several critical issues regarding the performance of ADCs are still being discussed and investigated. Indeed, in the past few years, several groups have reported that, changing the number and position of the drug payloads in the ADCs, affects the pharmacokinetics, drug release rates, and biological activity. The use of conventional heterogeneous conjugation methods for ADC preparation results in the drug/antibody ratio and connecting position of the payload having stochastic distributions. Therefore, it is important to investigate how these potential problems can be circumvented through site-specific conjugation. Herein, various site-specific chemical conjugation strategies with native mAbs that are currently used for the production of ADCs, including residue-selective labeling for generating ADCs, disulfide rebridging, and affinity-peptide-mediated site-specific chemical conjugation technologies, are reviewed and described.     

Application of Synchrotron Radiation for Studying Detonation and Shock‐Wave Processes

A new method of remote investigation of detonation and shockwave processes with the use of synchrotron radiation is proposed. The facility used for the first experiments with measurement of density and smallangle xray scattering in detonation of condensed explosives is described. The high time and spatial resolution of the techniques proposed allows one to determine the character and mechanism of destruction of the condensed phase and the growth dynamics of new structures, including crystalline ones, in detonation flows. The capabilities of the new technique are described.     

Kinetic Study of Co-b-Zeolite for Selective Catalytic Reduction

The effects of grain size, space velocity, temperature and reactant concentration on the kinetics of NOx reduction with propane over Co-b-zeolite catalyst were investigated. The external mass transfer phenomenon was examined by varying the space velocity. The results show that the transfer can be negligible when the space velocity is greater than 60000 h-1 in low temperature range. However, the transfer exists at high temperatures even when the space velocity reaches a high level. Variation of the catalyst grain size from 0.05 to 0.125 mm does not change the conversion rate of NOx. The concentrations of components, NOx, C3H8 and O2, were also investigated to have a better understanding of mechanism. Based on the experimental data, the selectivity formula was proposed. The results shows that lower temperature is helpful to get higher selectivity as the activation energy of hydrocarbon oxidation, Ea,2, is greater than that of NOx reduction, Ea,1, (Ea,2>Ea,1). High NOx concentration and low C3H8 concentration are beneficial to high selectivity. However in order to maintain high activity simultaneously, the temperature and C3H8 concentration should be high enough to promote NOx reduction. 10%(j) H2O and 75′10-6(j) SO2 were introduced into the reaction system, and Co-b-zeolite shows strong resistance to water and SO2.     

Radiolabelled Cyclic Bisarylmercury: High Chemical and in vivo Stability for Theranostics

We show the synthesis of an in vivo stable mercury compound with functionality suitable for radiopharmaceuticals. The designed cyclic bisarylmercury was based on the water tolerance of organomercurials, higher bond dissociation energy of Hg−Ph to Hg−S, and the experimental evidence that acyclic structures suffer significant cleavage of one of the Hg−R bonds. The bispidine motif was chosen for its in vivo stability, chemical accessibility, and functionalization properties. Radionuclide production results in ^197(m)HgCl₂(aq), so the desired mercury compound was formed via a water-tolerant organotin transmetallation. The Hg-bispidine compound showed high chemical stability in tests with an excess of sulfur-containing competitors and high in vivo stability, without any observable protein interaction by human serum assay, and good organ clearance demonstrated by biodistribution and SPECT studies in rats. In particular, no retention in the kidneys was observed, typical of unstable mercury compounds. The ^natHg analogue allowed full characterization by NMR and HRMS.     

Properties and Performances of High Purity Corundum Bricks for Chemical and Petrochemical Industries in China

The properties and performances of high purity corundum bricks for the refractory linings of the gasifiers in the ammonia and ethene synthesis and carbon black reaction furnaces in China are described.The high purity corundum bricks are characterized by high refractoriness,hot strength,dimensional stability and chemical inertness at elevated temperature,Their performances in the gasifiers and carbon black furnaces are very satisfied ,The failure mechansims of the refractory lining are discussed on the basis of the petrographic analysis.     

Appendix:Abstracts of Journal of Chemical Industry and Engineering(China)

A new plate-to-plate method for performanceprediction of azeotropic distillation processes isdeveloped.Azeotropic distillation is character-ized by the strong interaction among componentsand by a samll number of components involved.By plate-to-plate method,the number of intera-rive variables depends only on the number ofcomponents,therefore a combination of theplate-to-plate approach and the Newton-     

Formaldehyde as a Chemical Defence Agent of Fruiting Bodies of Mycena rosea and its Role in the Generation of the Alkaloid Mycenarubin C

Mycenarubin C, a previously unknown red pyrroloquinoline alkaloid, was isolated from fruiting bodies of the mushroom Mycena rosea and its structure was elucidated mainly by NMR spectroscopy and mass spectrometry. Unlike mycenarubin A, the major pyrroloquinoline alkaloid in fruiting bodies of M. rosea, mycenarubin C, contains an eight-membered ring with an additional C₁ unit that is hitherto unprecedented for pyrroloquinoline alkaloids known in nature. Incubation of mycenarubin A with an excess of formaldehyde revealed that mycenarubin C was generated nearly quantitatively from mycenarubin A. An investigation into the formaldehyde content of fresh fruiting bodies of M. rosea showed the presence of considerable amounts of formaldehyde, with values of 5 μg per gram of fresh weight in fresh fruiting bodies. Although mycenarubin C did not show bioactivity against selected bacteria and fungi, formaldehyde inhibits the growth of the mycoparasite Spinellus fusiger at concentrations present in fruiting bodies of M. rosea. Therefore, formaldehyde might play an ecological role in the chemical defence of M. rosea against S. fusiger. In turn, S. fusiger produces gallic acid—presumably to detoxify formaldehyde by reaction of this aldehyde with amino acids and gallic acid to Mannich adducts.     

Physico‐Chemical Processes for Landfill Leachate Treatment: Experiments and Mathematical Models

Abstract

In this study, the adsorption of synthetic landfill leachate onto four kinds of activated carbon has been investigated. From the equilibrium and kinetics experiments, it was observed that coal based PAC presented the highest organic pollutants removal efficiency (54%), followed by coal based GAC (50%), wood based GAC (33%) and wood based PAC (14%). The adsorption equilibrium of PAC and GAC was successfully predicted by Henry‐Freundlich adsorption model whilst LDFA+Dual isotherm Kinetics model could describe well the batch adsorption kinetics. The flocculation and flocculation–adsorption experiments were also conducted. The results indicated that flocculation did not perform well on organics removal because of the dominance of low molecular weight organic compounds in synthetic landfill leachate. Consequently, flocculation as pretreatment to adsorption and a combination of flocculation–adsorption could not improve much the organic removal efficiency for the single adsorption process.     

Preparation of Palladium-Silica Conjugated Membrane for Selective Hydrogen Permeation

Palladium membranes were prepared on an a-alumina support by metal-organic compound chemical vapor deposition (MOCVD) method from palladium(Ⅱ) acetate precursor. Permeation properties of hydrogen and helium gas were studied as a function of the number of times of deposition of palladium on the peeling off phenomenon of palladium, which is common in electroless plated membrane, was observed. Silica was introduced into the pores to prevent the palladium grain from peeling off. The palladium-silica conjugated membrane does not show the peeling off phenomenon and can withstand the high temperature up to 800CCCC which is the upper limit of our apparatus. The separation factor for hydrogen gas over carbon dioxide gas was improved with the increase of number of times of silica coating by sacrificing the H2 permeation and finally increased to four times. The improvement on the separation of hydrogen gas over carbon dioxide for palladium-silica conjugated membrane was evaluated and a model of permeation pattern     

25CN-NBOH: A Selective Agonist for in vitro and in vivo Investigations of the Serotonin 2A Receptor

4-(2-((2-hydroxybenzyl)amino)ethyl)-2,5-dimethoxybenzonitrile (25CN-NBOH) was first reported as a potent and selective serotonin 2A receptor (5-HT_2AR) agonist in 2014, and it has since found extensive use as a pharmacological tool in a variety of in vitro, ex vivo and in vivo studies. 25CN-NBOH is readily available from a synthetic perspective using standard chemical transformations, and displays favorable physiochemical properties in terms of stability and solubility. Due to its superior selectivity for 5-HT_2AR, 25CN-NBOH has been used to investigate the effects of selective 5-HT_2AR activation in vivo, and has thus become an important pharmacological tool for the exploration of 5-HT_2AR signaling in a range of animal models. In the present review, we outline the discovery of 25CN-NBOH, its pharmacological profile and major findings from studies where it has been used.     

2004 Review of China''''s Petroleum and Chemical Industry

Economy in Chinese petroleum andchemical industry is in very good shapein 2004, the major characteristics of theeconomic operation are: production andbenefit has been growing synchronously,sales income and realized profit both havemade the best in history; product struc-ture has been further adjusted, marketdemand brisk, price keep increasing; im-port and export trade has been active,export earned foreign exchange hasjumped impressively.     

Selective Affimers Recognise the BCL-2 Family Proteins BCL-xL and MCL-1 through Noncanonical Structural Motifs**

Abstract : The BCL-2 family is a challenging group of proteins to target selectively due to sequence and structural homologies across the family. Selective ligands for the BCL-2 family regulators of apoptosis are useful as probes to understand cell biology and apoptotic signalling pathways, and as starting points for inhibitor design. We have used phage display to isolate Affimer reagents (non-antibody-binding proteins based on a conserved scaffold) to identify ligands for MCL-1, BCL-x_L, BCL-2, BAK and BAX, then used multiple biophysical characterisation methods to probe the interactions. We established that purified Affimers elicit selective recognition of their target BCL-2 protein. For anti-apoptotic targets BCL-x_L and MCL-1, competitive inhibition of their canonical protein-protein interactions is demonstrated. Co-crystal structures reveal an unprecedented mode of molecular recognition; where a BH3 helix is normally bound, flexible loops from the Affimer dock into the BH3 binding cleft. Moreover, the Affimers induce a change in the target proteins towards a desirable drug-bound-like conformation. These proof-of-concept studies indicate that Affimers could be used as alternative templates to inspire the design of selective BCL-2 family modulators and more generally other protein-protein interaction inhibitors.     

BASF NanoSelect? Technology: Innovative Supported Pd- and Pt-based Catalysts for Selective Hydrogenation Reactions

An innovative BASF catalyst manufacturing technology (NanoSelect?) is introduced which allows production of heterogeneous catalysts with excellent control over metal crystallite sizes. NanoSelect? technology enabled the development of Pd catalysts which are lead-free Lindlar catalyst replacements in alkyne-to-cis-alkene hydrogenations. NanoSelect? Pt catalysts showed excellent chemoselectivity in substituted nitro-arene hydrogenation reactions without build-up of hydroxylamine intermediates. All NanoSelect? produced catalysts show markedly higher activity per gram of metal leading to ten-fold less use of precious metal.     

Organometallic Compounds: An Opportunity for Chemical Biology?

Organometallic compounds are renowned for their remarkable applications in the field of catalysis, but much less is known about their potential in chemical biology. Indeed, such compounds have long been considered to be either unstable under physiological conditions or cytotoxic. As a consequence, little attention has been paid to their possible utilisation for biological purposes. Because of their outstanding physicochemical properties, which include chemical stability, structural diversity and unique photo- and electrochemical properties, however, organometallic compounds have the ability to play a leading role in the field of chemical biology. Indeed, remarkable examples of the use of such compounds-notably as enzyme inhibitors and as luminescent agents-have recently been reported. Here we summarise recent advances in the use of organometallic compounds for chemical biology purposes, an area that we define as "organometallic chemical biology". We also demonstrate that these recent discoveries are only a beginning and that many other organometallic complexes are likely to be found useful in this field of research in the near future.     

Chemical Analysis of Magnesia and Magnesia-Alumina Refractory Materials——Gravimetric method for determination of loss on ignition

GB/T 5069.1-1985 1 Scope This standard specifies the gravimetric method for determination of loss on ignition. This standard is used for the determination of loss on ignition of magnesia and magnesia-alumina refractory materials. Determination range: ≥…     

Ethical Standards for Publication in Chinese Journal of Chemical Engineering

Chinese Journal of Chemical Engineering (CJChE) is a publication of the Chemical Industry and Engineering Society of China (CIESC) dedicated to present the original contributions of knowledge with permanent value from chemical engineering researchers and technical staff of process industries in China and the world. The editors-in-chief, associate editors-in-chief and