Endergonic synthesis driven by chemical fuelling

Nature Synthesis, Год журнала: 2024, Номер 3(6), С. 707 - 714

Опубликована: Март 11, 2024

Abstract Spontaneous chemical reactions proceed energetically downhill to either a local or global minimum, limiting possible transformations those that are exergonic. Endergonic do not spontaneously and require an input of energy. Light has been used drive number deracemizations thermodynamically unfavourable bond-forming reactions, but is restricted substrates can absorb, directly indirectly, energy provided by photons. In contrast, anabolism involves uphill powered fuels. Here we report on the transduction from artificial fuel Diels–Alder reaction. Carboxylic acid catalysed carbodiimide-to-urea formation chemically orthogonal reaction diene dienophile, transiently brings functional groups into close proximity, causing otherwise prohibited cycloaddition in modest yield (15% after two fuelling cycles) with high levels regio- (>99%) stereoselectivity (92:8 exo : endo ). Kinetic asymmetry cycle ratchets away equilibrium distribution Diels–Alder:retro-Diels–Alder products. The driving endergonic occurs through ratchet mechanism (an information ratchet, depending synthetic protocol), reminiscent how molecular machines directionally bias motion. Ratcheting synthesis potential expand chemistry toolbox terms reactivity, complexity control.

Язык: Английский

---

Artificial Homeostasis Systems Based on Feedback Reaction Networks: Design Principles and Future Promises

Angewandte Chemie International Edition, Год журнала: 2024, Номер 63(14)

Опубликована: Янв. 16, 2024

Abstract Feedback‐controlled chemical reaction networks (FCRNs) are indispensable for various biological processes, such as cellular mechanisms, patterns, and signaling pathways. Through the intricate interplay of many feedback loops (FLs), FCRNs maintain a stable internal environment. Currently, creating minimalistic synthetic cells is long‐term objective systems chemistry, which motivated by natural integrity. The design, kinetic optimization, analysis to exhibit functions akin those cell still pose significant challenges. Indeed, reaching homeostasis essential engineering components. However, maintaining in artificial against agitations difficult task. Several events can provide us with guidelines conceptual understanding homeostasis, be further applicable designing systems. In this regard, we organize our review driven at different length scales, including homogeneous, compartmentalized, soft material First, stretch quick overview molecular supramolecular systems, toolbox nonlinear homeostatic Moreover, existing history their advanced self‐correcting, regulating properties also emphasized.

Язык: Английский

---

Stepwise Operation of a Molecular Rotary Motor Driven by an Appel Reaction

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(7), С. 4467 - 4472

Опубликована: Фев. 6, 2024

To date, only a small number of chemistries and chemical fueling strategies have been successfully used to operate artificial molecular motors. Here, we report the 360° directionally biased rotation phenyl groups about C–C bond, driven by stepwise Appel reaction sequence. The motor molecule consists biaryl-embedded phosphine oxide phenol, in which full around biaryl bond is blocked P–O oxygen atom on rotor being too bulky pass stator. Treatment with SOCl2 forms cyclic oxyphosphonium salt (removing oxide), temporarily linking Conformational exchange via ring flipping then allows stator twist back forth past previous limit rotation. Subsequently, opening tethered intermediate chiral alcohol occurs preferentially through nucleophilic attack one face. Thus, original reformed net directional over course two-step Each repetition SOCl2–chiral additions generates another Using same sequence derivative that atropisomers rather than fully rotating results enantioenrichment, suggesting that, average, rotates "wrong" direction once every three cycles. interconversion oxides form temporary tethers enable rotational barrier be overcome adds available for generating chemically fueled kinetic asymmetry systems.

Язык: Английский

---

The Multifunctional Role of Templates in Chemically Fueled Dynamic Combinatorial Libraries

ChemSystemsChem, Год журнала: 2025, Номер unknown

Опубликована: Янв. 10, 2025

Abstract RNA is an information‐carrying molecule that instructs protein synthesis, but it also functions as a catalyst in so‐called ribozymes. Here, we study this multifunctional character using dynamic combinatorial library powered by chemical fuel. On the one hand, demonstrate templates oligomerization and inhibits deoligomerization. other show can be structural element formation of hydrogels. Moreover, its hydrogel, degradation nucleases accelerated. Thus, have role beyond blueprints, protectors, selectors. Template‐oligomer interactions create new (micro)environments might affect evolutionary dynamics.

Язык: Английский

---

Factors to Consider for Synthesis in 1536-Well Plates─An Amide Coupling Case Study for PROTAC Synthesis

The Journal of Organic Chemistry, Год журнала: 2025, Номер unknown

Опубликована: Фев. 2, 2025

Ultra high-throughput chemistry carried out in 1536-well plates is increasingly utilized for reaction optimization protocols and direct-to-biology (D2B) platforms, where nanomolar quantities of the final product are directly assessed biochemical or cellular activity without purification. As their popularity increases, it crucial that synthesis these molecules reliable reproducible. Research our laboratories has identified several nuances amide couplings when performed on nanoscale result poor translation from to batch-scale reactions. This case study presents a coupling synthesize 700 PROTAC molecules, which range factors success nanoscale, despite having no influence conversion batch. work guide chemists consider working importance drawing conclusions synthesis.

Язык: Английский

---

Timed Formation and Aging of Complex Coacervates Using a Volatile Salt

Macromolecules, Год журнала: 2025, Номер unknown

Опубликована: Март 26, 2025

Biomolecular condensates are liquid droplets formed by liquid–liquid phase separation and play a role in variety of cellular processes. In the past decade, there has been growing interest their study, often through use complex coacervates as models. Despite similar properties, limitation is inability to show time-dependent behavior, such aging, they typically structures thermodynamic equilibrium (or kinetically trapped). Here, we present simple protocol trigger delayed formation aging coacervates. We ammonium carbonate for this protocol, volatile salt that decreases ionic strength solution it decomposes. Using salt, were able program coacervate after delays ranging from hours days. This process can be repeated multiple times, decomposition leaves no waste products. The mechanical properties also change over time with showing steady increase viscosity reminiscent condensates. Since element causes temporal evolution not coacervates, does require any synthesis easily adapted

Язык: Английский

---

Endergonic synthesis driven by chemical fuelling

Опубликована: Янв. 17, 2024

Spontaneous chemical reactions proceed energetically downhill to either a local or global minimum, limiting possible transformations those that are exergonic. Endergonic do not spontaneously and require an input of energy. Light has been used drive number deracemisations thermodynamically unfavourable bond-forming reactions, but is restricted substrates can absorb, directly indirectly, energy provided by photons. In contrast, anabolism involves uphill powered fuels. Here we report on the transduction from artificial fuel Diels–Alder reaction. Carboxylic acid catalysed carbodiimide-to-urea formation chemically orthogonal reaction diene dienophile, transiently brings functional groups into close proximity, causing otherwise prohibited cycloaddition in modest yield (15% after two fuelling cycles) with high levels regio- (>99%) stereoselectivity (92:8 exo:endo). Kinetic asymmetry cycle ratchets away equilibrium distribution Diels–Alder:retro-Diels–Alder products. The driving endergonic occurs through ratchet mechanism (an information ratchet, depending synthetic protocol), reminiscent how molecular machines directionally bias motion. Ratcheting synthesis potential expand chemistry toolbox, offering new paradigms reactivity, complexity control.

Язык: Английский

---

Self-Optimizing Flow Reactions for Sustainability: An Experimental Bayesian Optimization Study

ACS Sustainable Chemistry & Engineering, Год журнала: 2024, Номер 12(26), С. 10002 - 10010

Опубликована: Июнь 19, 2024

Self-optimizing flow reactors have received significant attention in recent years, with Bayesian optimization (BO) being identified as the most effective method for reaction optimization. However, there are many different approaches using BO algorithms, which is overwhelming experimentalists. Here, pharmaceutically relevant amide coupling reactions, we explore "best practices" three areas, to promote efficient design of sustainable processes: (1) A high extent exploration an algorithm was deemed necessary ensure a good space overview. (2) Yield optimized within small experimental budget, while minimizing environmental impact, by setting up objective function penalties (e.g., excess reagent usage). (3) An auxiliary data set appeared behave well same substrates reagent, but provided no advantage when substantially lower reactivity. We envisage that these general recommendations will aid chemists utilizing automated development reactions.

Язык: Английский

---

Transient polymers through carbodiimide-driven assembly

Опубликована: Март 8, 2024

Biochemical systems make use of out-of-equilibrium polymers generated under kinetic control. Inspired by these systems, many abiotic supramolecular driven chemical fuel reactions have been reported. Conversely, based on transient covalent bonds received little attention, even though they the potential to complement generating structures stronger and offering a straightforward tuning reaction kinetics. In this study, we show that simple aqueous dicarboxylic acids give poly(anhydrides) when treated with carbodiimide EDC. Transient molecular weights exceeding 15,000 are which then decompose over course days. Disassembly kinetics can be controlled using substituent effects in monomer design. The impact solvent polarity, concentration, concentration polymer properties lifetimes has investigated. results reveal substantial control assembly disassembly kinetics, highlighting for fine-tuned nonequilibrium polymerization systems.

Язык: Английский

---

Controlling carbodiimide-driven reaction networks through the reversible formation of pyridine adducts

Опубликована: Апрель 30, 2024

Carbodiimide-driven anhydride formation from carboxylic acids is useful in a variety of non-equilibrium systems. While multiple strategies to control deactivation rates (anhydride hydrolysis) have been reported, over activation formation) currently limited. We show that pyridines reversibly form adducts with 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide methiodide water. These are unreactive and thus reduce the rate while prolonging carbodiimide lifetime. The best results obtained 4-methoxypyridine. This strategy can be used transient polymer network hydrogels, one example increasing time reach peak modulus by 86% lifetime 43%.

Язык: Английский

---