Tandem Chain Research Articles

Supporting a capital-constrained supplier with mixed pre-shipment financing facilities

This study considers a tandem supply chain (S.C.) in which a credit-worthy retailer cooperates with a capital-constrained supplier to manufacture products. The retailer can use two major pre-shipment financing options, either cash in advance (CIA) or pricing support purchase order financing (PSPOF), to fund the supplier’s operations. A model is developed to examine the interactions among the entities. The retailer can choose the prepayment modality, purchase price and order quantity. The supplier decides on the production input and loan amount. A Karush-Kuhn-Tucker optimality analysis is used to characterise the properties of the retailer’s ordering and financing strategy: (1) The supplier might embezzle the CIA if the purchasing and financing contract is not well-designed; therefore, the retailer should establish some restrictions on the order price and CIA amount. (2) The retailer’s optimal decision about the quantity to purchase is independent of the financing strategy. (3) Because these schemes are interchangeable, multiple optimal financing portfolios consisting of CIA and/or PSPOF are possible. (4) The optimal dual-financing scheme maximises the retailer’s profit and integrates the S.C. Thus, the scheme can eliminate the effect of double-marginalisation. (5) As the supplier becomes more reliable, the retailer should increase the usage of PSPOF and purchasing quantity.

The Introduction of the Radical Cascade Reaction into Polymer Chemistry: A One-Step Strategy for Synchronized Polymerization and Modification.

SummaryPolymerization and modification play central roles in polymer chemistry and are generally implemented in two steps, which suffer from the time-consuming two-step strategy and present considerable challenge for complete modification. By introducing the radical cascade reaction (RCR) into polymer chemistry, a one-step strategy is demonstrated to achieve synchronized polymerization and complete modification in situ. Attributed to the cascade feature of iron-catalyzed three-component alkene carboazidation RCR exhibiting carbon-carbon bond formation and carbon-azide bond formation with extremely high efficiency and selectivity in one step, radical cascade polymerization therefore enables the in situ synchronized polymerization through continuous carbon-carbon bond formation and complete modification through carbon-azide bond formation simultaneously. This results in a series of α, β, and γ poly(amino acid) precursors. This result not only expands the methodology library of polymerization, but also the possibility for polymer science to achieve functional polymers with tailored chemical functionality from in situ polymerization.

Synthesis of amphiphilic copolymers based on dendritic polyethylene grafted by polyhydroxyethylmethacrylate and polyhydroxypropylmethacrylate and their use for construction of nanoparticles

By grafting from approach amphiphilic grafted copolymers with a hydrophobic core based on dendritic polyethylene and hydrophilic grafts of polyhydroxyethylmethacrylate (PHEMA) and polyhydroxypropylmethacrylate (PHPMA) were synthesized by tandem chain walking copolymerization and ATRP. Copolymers with molar mass 160–1400 kg/mol and ∼50–90% of hydrophilic grafts were obtained. Core-shell nanoparticles with very narrow size distribution were prepared from the copolymers by solvent displacement method. Particles diameter was efficiently regulated by molar mass of the copolymers in the range of 60–180 nm. We demonstrated that these nanoparticles can act as nanocontainers for hydrophobic Nile red dye, achieving up to 25% encapsulation efficiency. Dendritic polyethylene (dPE) nanoparticles with biocompatible polar PHEMA and PHPMA shell can find application in nanocatalysis and cargo delivery.

Syntheses of Papyracillic Acids: Application of the Tandem Chain Extension–Acylation Reaction

A synthetic approach to the papyracillic acid family of natural products has been developed. The spiroacetal core is rapidly assembled through an unprecedented zinc carbenoid-mediated tandem chain extension-acylation reaction. Subsequent functional group manipulation provided access to papyracillic acid B and 4-epi-papyracillic acid C. The successful preparation of these molecules resulted in the clarification of structural assignments of members of this family of natural products.

β-Proline Derivatives through Tandem Chain Extension–Mannich Reaction

Key words chain extension - zinc carbenoids - β-proline - Mannich reaction - tandem reaction

Monitoring of Pediatric Patients With Malignant Hematological Diseases After Allogeneic HSCT

We describe the implementation of short tandem repeats-polymerase chain reaction (STR-PCR) chimerism analyses coupled with reverse transcription PCR detection of recurrent translocations characteristic for childhood leukemia in monitoring of patients after allogeneic hematopoietic stem cell transplantation in Serbia and the first clinical results thereof. Chimerism and minimal residual disease were regularly analyzed from blood and marrow samples of 26 pediatric patients taken after stem cell transplantation with a median follow-up of 17.6 months. Our results demonstrate that STR-based chimerism monitoring is sufficient in establishing the origin of engrafted cells after transplantation and in detecting graft rejection, but more specific and more sensitive method is necessary for identifying patients with threatening leukemia relapse.

Tandem chain extension–Mannich reaction: an approach to β-proline derivatives

A zinc carbenoid-initiated chain extension reaction provides access to an organometallic intermediate, which can be used to capture activated imines. Deprotection of the nitrogen and reduction provides access to racemic derivatives of β-proline. The relative stereochemistry of the β-proline can be controlled through use of different activating groups on the imine nitrogen.

A Combined DFT and NMR Investigation of the Zinc Organometallic Intermediate Proposed in the Syn-Selective Tandem Chain Extension–Aldol Reaction of β-Keto Esters

The tandem chain extension-aldol (TCA) reaction of β-keto esters provides an α-substituted γ-keto ester with an average syn:anti selectivity of 10:1. It is proposed that the reaction proceeds via a carbon-zinc bound organometallic intermediate potentially bearing mechanistic similarity to the Reformatsky reaction. Evidence, derived from control Reformatsky reactions and a study of the structure of the TCA intermediate utilizing DFT methods and NMR spectroscopy, suggests the γ-keto group of the TCA intermediate plays a significant role in diastereoselectivity observed in this reaction. Such coordination effects have design implications for future zinc mediated reactions.

Polydispersity-driven shift in the lamellar mesophase composition window of PEO-PB-PEO triblock copolymers

The influence of broad and continuous center block polydispersity on the melt-phase self-assembly of OBO triblock copolymers (O = poly(ethylene oxide) and B = poly(1,4-butadiene)) is reported for a series of samples derived from tandem chain transfer ring-opening metathesis polymerization (ROMP-CT) and anionic ring-opening polymerization (AROP). By virtue of the polymerization techniques employed in these syntheses, the midblocks exhibit polydispersity indices Mw/Mn = 1.75, whereas the end blocks have relatively narrow dispersities Mw/Mn ≤ 1.25. Using a combination of small-angle X-ray scattering (SAXS) and transmission electron microscopy (TEM) to characterize these materials and their narrow dispersity homologues derived from anionic polymerization, we demonstrate that the combination of both chain length and composition polydispersity inherent in these polydisperse triblocks shifts the composition window of stability for the lamellar mesophase. Furthermore, these studies reveal that polydispersity in the center B segments of these OBO triblocks results in large lamellar domain spacing increases, enables stable coexistence of two morphologies in a single sample, and frustrates lattice ordering in a composition-dependent manner.

More insight into tandem ROMP and ADMET polymerization for yielding reactive long-chain highly branched polymers and their transformation to functional polymer nanoparticles

Tandem chain transfer ring-opening metathesis polymerization (ROMP-CT) and acyclic diene metathesis (ADMET) polymerization were carried out in a controlled one-pot procedure, and behaved noticeable differences in polymerization of monomers by different ruthenium catalysts, whereas there indeed had been two distinctly polymerization stages. In the first one, ROMP-CT of functional monomers was conducted in the presence of a symmetrical multi-olefin as chain transfer agent within various reaction time scales, yielding linear telechelic polymers. Next, ADMET polymerization of telechelic polymers was performed and generated a series of reactive long-chain highly branched polymers (LCHBPs) with acrylate and/or azobenzene groups having molecular weights of 8.5–47.9 kDa under varied conditions. LCHBPs were fully characterized by several techniques, and interestingly, UV–vis analysis displayed the specific peak at 278 nm, which offered a new evidence for the existence of internal acrylate structure on the LCHBP backbone, and supported the highly branched architecture of polymers. LCHBP containing a number of pendent acrylate groups was readily converted, by thiol-Michael addition click reaction, to novel thiol-functionalized intra-molecular crosslinked unimolecular polymer nanoparticles with diameter of 40–60 nm, which provided a facile method for post-functionalization of branched polymers.

The tandem chain extension aldol reaction used for synthesis of ketomethylene tripeptidomimetics targeting hPEPT1

The rationale for targeting the human di-/tripeptide transporter hPEPT1 for oral drug delivery has been well established by several drug and prodrug cases. The aim of this study was to synthesize novel ketomethylene modified tripeptidomimetics and to investigate their binding affinity for hPEPT1. Three related tripeptidomimetics of the structure H-Phe-ψ[COCH(2)]-Ser(Bz)-X(aa)-OH were synthesized applying the tandem chain extension aldol reaction, where amino acid derived β-keto imides were stereoselectively converted to α-substituted γ-keto imides. In addition, three corresponding tripeptides, composed of amide bonds, were synthesized for comparison of binding affinities. The six investigated compounds were all defined as high affinity ligands (K(i)-values <0.5 mM) for hPEPT1 by measuring the concentration dependent inhibition of apical [(14)C]Gly-Sar uptake in Caco-2 cells. Consequently, the ketomethylene replacement for the natural amide bond and α-side chain modifications appears to offer a promising strategy to modify tripeptidic structures while maintaining a high affinity for hPEPT1.

Meiotic chromosome configurations in triploid and heteroploid mosaic males of Crassostrea gigas and Crassostrea ariakensis

Reversion from triploids to diploids or heteroploid mosaics may make the revertants recover reproductive ability and lose their aquacultural advantages. Meiotic chromosomes in triploids and mosaics of Crassostrea gigas and Crassostrea ariakensis were studied. Pachytene spermatocytes showed incomplete trivalent formation, varying 64–72% in C. gigas and 62–69% in C. ariakensis. At metaphase I, trivalents, bivalents and univalents occurred in various combinations. Trivalents occurred in all spermatocytes, ranged 6–10 per spermatocyte and averaged 8.53–8.97 in C. gigas and 8.49–8.95 in C. ariakensis. Univalents and bivalents appeared in 59.2–72.1% of the spermatocytes in C. gigas, and ranged 0.77–1.39 and 1.01–1.51 per spermatocyte respectively. In C. ariakensis, they occurred in 57.5–81% of the spermatocytes, and ranged 0.9–1.32 and 1.03–1.35 respectively. The most common trivalent was formed by a bivalent with the third chromosome attaching to its side to form ‘long-tail-cross’ or ‘t’ or ‘frying-pan’-shaped configurations that constituted 65.7% and 59.9% of the trivalents in C. gigas and C. ariakensis respectively. Other kinds of trivalent associations included tandem chains (14.7%, 16.5%), closed circles or triangles (5.3%, 9.8%), convergent ‘T’ or ‘Y’ (5.8%, 7.4%) and unclassified configurations (8.5%, 6.4%). Diploid spermatocytes were not observed from mosaics, although they showed considerable proportions of ‘diploid’ cells in their gills.

ChemInform Abstract: Tandem Chain Extension—Iodomethylation Reactions: Formation of α‐Functionalized γ‐Keto Carbonyls.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Generation, Affinity Maturation, and Characterization of a Human Anti-Human NKG2D Monoclonal Antibody with Dual Antagonistic and Agonistic Activity

In humans, NKG2D is an activating receptor on natural killer (NK) cells and a costimulatory receptor on certain T cells and plays a central role in mediating immune responses in autoimmune diseases, infectious diseases, and cancer. Monoclonal antibodies that antagonize or agonize immune responses mediated by human NKG2D are considered to be of broad and potent therapeutic utility. Nonetheless, monoclonal antibodies to NKG2D that are suitable for clinical investigations have not been published yet. Here, we describe the generation, affinity maturation, and characterization of a fully human monoclonal antibody to human NKG2D. Using phage display technology based on a newly generated naïve human Fab library in phage display vector pC3C followed by a tandem chain shuffling process designed for minimal deviation from natural human antibody sequences, we selected a human Fab, designated KYK-2.0, with high specificity and affinity to human NKG2D. KYK-2.0 Fab blocked the binding of the natural human NKG2D ligands MICA, MICB, and ULBP2 as potently as a commercially available mouse anti-human NKG2D monoclonal antibody in immunoglobulin G (IgG) format. Conversion of KYK-2.0 Fab to IgG1 resulted in subnanomolar avidity for human NKG2D. KYK-2.0 IgG1 was found to selectively recognize defined subpopulations of human lymphocytes known to express NKG2D, that is, the majority of human CD8+, CD16+, and CD56+ cells as well as a small fraction of human CD4+ cells. In solution, KYK-2.0 IgG1 interfered with the cytolytic activity of ex vivo expanded human NK cells. By contrast, immobilized KYK-2.0 IgG1 was found to strongly induce human NK cell activation. The dual antagonistic and agonistic activity promises a wide range of therapeutic applications for KYK-2.0 IgG1 and its derivatives.

Formation of γ-Lactones through CAN-Mediated Oxidative Cleavage of Hemiketals

The generation of substituted gamma-lactones can be accomplished through application of a tandem chain extension-aldol reaction, followed by CAN-mediated oxidative cleavage of the aldol product. The oxidative cleavage requires the intermediacy of a hemiketal and the presence of an alpha-heteroatom. Formation of the gamma-lactone through the oxidative cleavage is used to assign stereochemistry of the aldol reaction and as the final step in a short synthesis of members of the phaseolinic acid family of natural products.

Tandem chain extension–iodomethylation reactions: formation of α-functionalized γ-keto carbonyls

Sequential exposure of a zinc-organometallic intermediate, generated through a zinc carbenoid-mediated chain extension reaction of a β-keto carbonyl, to trimethylsilylchloride and iodine provided regioselective formation of an α-iodomethyl-γ-keto carbonyl. The iodomethyl functionality can be further manipulated to provide side chains that are potential mimics of α-amino acid side chains.

Stereocontrolled Formation of Ketomethylene Isosteres through Tandem Chain Extension Reactions

A zinc-mediated chain extension reaction is the key step in the preparation of gamma-keto amides derived from amino acids. The use of tandem reaction sequences, in which the intermediate zinc enolate is trapped with electrophilic reagents, results in the incorporation of alpha-substituents, which mimic the side chains found in natural amino acid systems. Use of the chiral amino acid L-proline as a stereo-directing element provides a diastereoselective route to various ketomethylene isosteres.

ChemInform Abstract: Tandem Chain Extension—Aldol Reaction: Syn Selectivity with a Zinc Enolate.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform Abstract: Tandem Chain Extension—Homoenolate Formation: The Formation of α‐Methylated‐γ‐keto Esters.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Tandem chain extension-aldol reaction: syn selectivity with a zinc enolate.

A tandem chain extension-aldol reaction was developed in which beta-keto esters are transformed to alpha-substituted-gamma-keto esters in an efficient zinc-mediated, one-pot reaction. The diastereoselectivity of the reaction ranged from good to excellent with syn stereochemistry observed for beta-keto ester and amide substrates and anti-stereochemistry observed for a beta-keto imide. [reaction: see text]