Calix[5]arene Self‐Folding Cavitands: a New Family of Bio‐Inspired Receptors with Enhanced Induced Fit Behavior

Posted on 6 July 2023 by

Abstract

Self-folding cavitands represent the quintessential form of bioinspired synthetic receptors, featuring deep hydrophobic cavities that engage in host-guest chemistry reminiscent of that operating in biomolecules. Although remarkable proof-of-concept applications have been reported, the narrow and rigid spaces of the legacy resorcin[4]arene derived hosts constitute a liability towards the development of specific applications in catalysis, sensing or sequestration. While notable efforts to expand the size of the cavities have been reported, the development of confined spaces reproducing the highly adaptable nature of biological receptors is a largely unaddressed issue. This review summarizes the development of a new family of calix[5]arene derived self-folding cavitands displaying enhanced induced fit and conformational selection phenomena. Our approach capitalizes on hydrogen bonding preorganization rather than the covalent restriction approaches customary of conventional supramolecular chemistry.

A Tribute to Richard Lerner (1938–2021) who Encouraged a Glycobiology Approach to a Broad‐Spectrum Antiviral

Posted on 6 July 2023 by nConstantina Fotinou, nRaymond A. Dwekn

Abstract

Richard Lerner was a visionary polymath of the 20^th century; a medical doctor, chemist, immunologist, inventor, and founder of new scientific fields. As a tribute to his life and scientific achievements, we discuss his connection with Oxford University and the Glycobiology Institute and we discuss our research data on the host glycoprotein folding pathway and how its inhibition can lead to broad spectrum antiviral drugs. This host targeting approach for developing antiviral therapies has the advantage of being effective against many viruses, therefore can be used to prevent new epidemics to become pandemics.

Electrochemical Organic Synthesis in Aqueous Media

Posted on 30 June 2023 by nMengFan Li, nXu Chengn

Abstract

Conducting electrochemical organic synthesis in/on whole water media is undoubtedly a highly green approach, which avoids the usage of organic solvents, and sometimes organic supporting electrolytes. In this review, the electrochemical organic syntheses in/on whole water environment are reviewed, especially including the reactions conducted both in organic solvent and water for comparisons. This review discussed anodic and cathodic reaction, respectively, including the C−H oxidation, hydroxylation, dehydrogenative cross coupling, functionalization of alkenes, cathodic oxidation, hydrogenation, reductive cross coupling, and so on. As the reduction of CO₂, conversion biomass, and waste water disposal are frequently performed in water, and have already been reviewed recently. These topics are not included in this review.

Electrochemical Oxidation of Alcohols Using Halogen Mediators

Posted on 27 June 2023 by nKosuke Yamamoto, nMasami Kuriyama, nOsamu Onomuran

Abstract

The high importance of carbonyl compounds in organic synthesis and fine chemical industries has let the development of efficient and environmentally benign methods for the oxidation of alcohols be an important research field. Electrochemistry would be one of the ideal strategies to achieve green redox processes avoiding the use of chemical oxidants/reductants. Due to the relatively high oxidation potential of alcohols, indirect methods using redox mediators have often been employed for the electrochemical alcohol oxidation. Halide salts would be one of the most traditional but still common mediators owing to the advantage of wide commercial availability and cost-efficiency. This review summarized the electrogenerated active halogen-mediated transformations of prim- sec-, and tert-alcohols from the pioneering works to the recent examples. In addition, recent advances in the direct oxidation of alcohols are also presented.

Richard Lerner – Mentor, Colleague, and Friend

Posted on 27 June 2023 by nBenjamin F. Cravattn

Israel Journal of Chemistry, EarlyView.

Immunoglobulin Go: Synergy of Combinatorics for Catalysis

Posted on 21 June 2023 by

Abstract

The maturation of B cells leads to the synthesis of highly evolved immunoglobulins (Igs) that enable efficient antigen-antibody recognition. Here we discuss a non-opportunistic, combinatorial concept of “maturation” of Igs in silico for the production of artificially-evolved immunocatalysts. Several recent breakthroughs including: (i) single B cell selection using microfluidic technology (ii) combinatorial approaches powered by library screening (iii) structural computing and machine learning, (iv) quantum mechanics/molecular mechanics (QM/MM) evaluations of catalytic reaction leading to optimistic prospect for the elaboration of more effective immunoglobulin-derived catalytic templates and redirection the selection process to a purely robotic procedure. The synergy of these approaches enable catalytic antibody become a great prospect for biomedical purposes. The most recent breakthroughs include therapeutic antibodies and catalytic Chimeric Antigen Receptors (catCARs) with controllable pharmacokinetic parameters.

Nature’s Blueprint: Chelation‐Assisted C−H Functionalization for Selective and Efficient Reactions in Aqueous Media

Posted on 31 May 2023 by nYini Wang, nXiandie Zhang, nJian Zhang, nGuofu Zhongn

Abstract

Efficient and sustainable strategies for C−H functionalization are crucial in organic synthesis. Bioinspired catalytic systems have emerged as promising alternatives to traditional synthetic methods. These systems draw inspiration from nature‘s ability to selectively functionalize complex molecules in water-based environments. Among these, chelation-assisted C−H functionalization stands out due to its ability to guide the substrate towards the active site of the catalyst, thereby controlling the selectivity of the reaction. This review focuses on the use of chelation assistance to enhance the efficiency and selectivity of bioinspired C−H functionalization reactions in aqueous media. We cover aliphatic, aromatic, and alkenyl C−H functionalization, as well as tandem C−H activation/cyclization, utilizing metallocycle intermediates. Additionally, we highlight the underlying mechanisms of these reactions for a deeper understanding and development of novel methodologies.

Antibody Libraries as Platforms to Exploring Target and Receptor Pleiotropy

Posted on 31 May 2023 by nChih‐Wei Lin, nKyung Ho Hann

Abstract

Monoclonal antibodies (mAbs) have become important classes in biopharmaceutical products. The selection of antibodies has traditionally been based on their binding affinity. New techniques and advancements in combinatorial antibody libraries have made it possible to isolate functional antibodies within cellular environments. These antibodies can act an agonist or antagonist provide valuable insights into the complexities of signal transduction and potentially leading to different cell responses or affecting cell behavior. Additionally, an in vivo selection system is utilized, which relies on cell migration to specific tissues, to generate antibodies that induce cells to differentiate and selectively migrate to particular tissues. Overall, the discovery of functional antibodies from antibody libraries has the potential to reveal receptor pleiotropism and pave opportunities to investigate cellular biology and uncover surprising discoveries in the areas of stem cells and cancer research.

Possible Approaches to Drug Delivery via Glutathione Transferase Proteins and Chitosan

Posted on 26 May 2023 by nBirgitta Sjödin, nPedram Farsi, nBengt Mannervikn

Abstract

Novel means of drug delivery are in great demand in particular for the administration of macromolecules. Glutathione transferase proteins can undergo cellular uptake and thereby deliver pharmaceutical cargo to intracellular sites. The proteins are soluble and can be produced in large quantities by facile bacterial expression. Molecular engineering may endow the proteins with signal sequences directing the delivery to specific intracellular targets and escape domains that facilitate cargo release from endosomes. Sequences providing high affinity for nucleic acids may find use in vaccines based on DNA or RNA. The combination of chitosan and glutathione transferase synergistically enhances the cellular uptake of the protein. Engineered glutathione transferase proteins offer great potential in the area of drug delivery research.

Synthesis and Chemiexcitation of a Distinct Chemiluminescent Luminophore based on a Curcumin Scaffold

Posted on 17 May 2023 by nRozan Tannous, nSara Gutkin, nPhil S. Baran, nDoron Shabatn

Abstract

Natural fluorogenic dyes are composed of unique molecular structures that could be harnessed for the design of new chemiluminescent luminophores. Here we demonstrated how to simply transform an emissive curcumin scaffold into a novel chemiluminescent luminophore. An appropriate bromo-curcumin intermediate was synthesized as a substrate for a Stille cross-coupling reaction with an adamantyl-stannane reagent. This late-stage functionalization afforded in one step a curcumin enolether precursor that can then be oxidized with singlet oxygen to produce a curcumin chemiluminescent luminophore. This curcumin dioxetane luminophore produced an intense light signal with an emission spectrum that correlates with its curcumin scaffold. This is the first example of a chemiluminescent luminophore that is based on the emissive nature of the curcumin molecular structure. We expect that the method described herein would be useful for the synthesis of new chemiluminescent luminophores by transforming other known emissive dyes into dioxetane precursors via the Stille cross-coupling approach.