Molecular Ratchets and Kinetic Asymmetry: Giving Chemistry Direction

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(23)

Published: April 3, 2024

Abstract Over the last two decades ratchet mechanisms have transformed understanding and design of stochastic molecular systems—biological, chemical physical—in a move away from mechanical macroscopic analogies that dominated thinking regarding dynamics in 1990s early 2000s (e.g. pistons, springs, etc), to more scale‐relevant concepts underpin out‐of‐equilibrium research sciences today. Ratcheting has established nanotechnology as frontier for energy transduction metabolism, enabled reverse engineering biomolecular machinery, delivering insights into how molecules ‘walk’ track‐based synthesisers operate, acceleration reactions enables be transduced by catalysts (both motor proteins synthetic catalysts), dynamic systems can driven equilibrium through catalysis. The recognition biology, their invention systems, is proving significant areas diverse supramolecular chemistry, covalent DNA nanotechnology, polymer materials science, heterogeneous catalysis, endergonic synthesis, origin life, many other branches science. Put simply, give chemistry direction. Kinetic asymmetry, key feature ratcheting, counterpart structural asymmetry (i.e. chirality). Given ubiquity processes significance behaviour function it surely just fundamentally important. This Review charts recognition, development ratchets, focussing particularly on role which they were originally envisaged elements machinery. Different kinetically asymmetric are compared, consequences discussed. These archetypal examples demonstrate inexorably equilibrium, rather than relax towards it.

Language: Английский

---

A molecular anion pump

Science, Journal Year: 2024, Volume and Issue: 385(6708), P. 544 - 549

Published: Aug. 1, 2024

Pumping ions against a concentration gradient through protein-based transporters is cornerstone of numerous biological processes. Mimicking this function by using artificial receptors remains daunting challenge, mainly because the difficulties in balancing between requirement for high binding affinities and precise on-demand ion capture release properties. We report trimeric hydrazone photoswitch-based receptor that converts light energy into work actively transporting chloride anion dichloromethane liquid membrane, functioning as molecular pump. The system manifests ease synthesis, bistability, excellent photoswitching properties, superb ON-OFF properties (difference up to six orders magnitude).

Language: Английский

---

Anion transporters based on halogen, chalcogen, and pnictogen bonds: towards biological applications

Chemical Science, Journal Year: 2024, Volume and Issue: 15(37), P. 15006 - 15022

Published: Jan. 1, 2024

Synthetic anion receptors based on sigma-hole interactions are increasingly used to transport anions across membranes. This article discusses the progress in field and prospects for biological applications.

Language: Английский

---

A multi-stimuli responsive [3]rotaxane based on hydrogen-bonded aramide azo-macrocycles

Chinese Chemical Letters, Journal Year: 2025, Volume and Issue: unknown, P. 110842 - 110842

Published: Jan. 1, 2025

Language: Английский

---

Controlling the transmembrane transport of chloride by dynamic covalent chemistry with azines

Chemical Science, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

This article presents the use of dynamic covalent chemistry in liposomal membranes to activate and modulate transmembrane transport chloride by addition different azine-containing compounds.

Language: Английский

---

Mechanosensitive and pH‐Gated Butterfly‐Shaped Artificial Ion Channel for High‐Selective K⁺ Transport and Cancer Cell Apoptosis

Advanced Materials, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 21, 2025

To advance the exploration of mechanisms underlying natural multi-gated ion channels, a novel butterfly-shaped biomimetic K+ channel GnC7 (n = 3, 4) is developed with dual mechanical and pH responsiveness, exhibiting unprecedented K+/Na+ selectivity (G3C7: 34.4; G4C7: 41.3). These channels constructed from poly(propylene imine) dendrimer benzo-21-crown-7-ethers achieve high transport activity (EC50: 0.72 µm for G3C7; 0.9 G4C7) due to their arc-like rotation. The dynamic mode relies on topology derived highly symmetrical core multiple intramolecular hydrogen bonds. can sense stimulus applied liposomes/cells then adapt rate accordingly. Furthermore, reversible ON/OFF switching realized through pH-controllable host-guest complexation. G4C7-induced ultrafast cellular efflux (70% within only 9 min) efficiently triggers mitochondrial-dependent apoptosis cancer cells by provoking endoplasmic reticulum stress accompanied drastic Ca2+ sparks. This work embodies multi-dimensional regulation functions; it will provide insights into behaviors biological analogs promote innovative design artificial therapeutic agents.

Language: Английский

---

Photo-Switchable Supramolecular Interactions Regulate K⁺ Transmembrane Transport and Cancer Cell Apoptosis

Journal of the American Chemical Society, Journal Year: 2025, Volume and Issue: unknown

Published: March 20, 2025

Natural channel proteins (NCPs) have numerous ion transport modes, but it remains a big challenge to replicate this trait by artificial systems. Herein, we present an azobenzene-incorporated single-chain random heteropolymers (RHPs)-derived biomimetic K+ P3, which can switch between three states ("ON," "Partially OFF," and "Totally OFF") in both liposomes cancer cells. The conformational adjustments of P3 activated light-modulating two groups supramolecular interactions ((1) hydrogen bonding π-π interactions; (2) host-guest interactions) realize these switches, resembling the protein mechanisms that govern activity. Underlying molecular are photoisomerization azobenzene moieties their complexation with β-cyclodextrin (β-CD), enabling exploit "one stone (azobenzene moiety), birds (supramolecular interactions)" strategy. Mechanistic investigations demonstrate P3-induced substantial efflux (a 50% drop within just 4 min) causes endoplasmic reticulum (ER) stress, intriguing Ca2+ sparks, enhanced reactive oxygen species (ROS), finally severe mitochondria-dependent apoptosis. This NCP-like (P3) is expected provide new opportunities for deeper understanding internal NCPs, as well treating other diseases.

Language: Английский

---

Manipulating the Isomerization of a Tris-azobenzene Cage by Anion Binding

Journal of the American Chemical Society, Journal Year: 2025, Volume and Issue: unknown

Published: April 22, 2025

Here, we report a C3-symmetric tris-azobenzene cage 1 comprising azobenzene cores and bis(urea) units. This system demonstrates efficient reversible photoisomerization unprecedented anion-mediated switching modes. Specifically, the phosphate anion induces concerted ZZZ → EEE isomerization with prolonged thermal relaxation (t1/2 = 37.5 h at 298 K). In contrast, bulky benzene-1,3,5-tricarboxylate enforces stepwise pathway (ZZZ EZZ EEZ EEE) rapid 54.4, 44.5, 12.9 min for each step). study represents first demonstration of selective control over multi-azobenzene switch, mimicking biological adaptability through environmental changes.

Language: Английский

---

Membrane Transport, Molecular Machines, and Maxwell's Demon

ChemSystemsChem, Journal Year: 2024, Volume and Issue: 6(3)

Published: Feb. 9, 2024

Abstract The spontaneous generation of transmembrane gradients is an important fundamental research goal for artificial nanotechnology. active transport processes that give rise to such directly mirror the famous Maxwell's Demon thought experiment, where a partitions particles between two chambers generate nonequilibrium state. Despite these similarities, discussion absent in literature on membrane transport. By contrast, emergence rational design principles molecular motors can trace its intellectual roots this experiment. This perspective highlights links and machines, argues understanding implications 19 th century experiment crucial future development processes.

Language: Английский

---

Single‐Stranded Nucleic Acid Transmembrane Molecular Carriers Based on Positively Charged Helical Foldamers

Advanced Science, Journal Year: 2024, Volume and Issue: 11(28)

Published: May 16, 2024

Abstract Transmembrane delivery of biologically active nucleic acids is an important process in cells and has inspired one to develop advanced drug techniques. In this contribution, molecular‐level single‐stranded acid transmembrane carriers are reported based on 3.2 nm long Huc's foldamers (A Orn Q 3 ) 8 ( m 2 with linearly helically aligned positive charges, respectively. These two not only show very strong DNA affinity via electrostatic interactions but also discriminatively bind (ss‐DNA) double‐stranded (ds‐DNA), corroborating the importance precise charge arrangement interactions. More importantly, these capable efficiently transporting ss‐DNA across lipid membranes, transport activity charges higher than that charges. Thus a type novel molecular positively charged helical introduced. Further, effective enhanced expression EGFP‐mRNA transfection experiments strongly demonstrates potential for RNA therapy.

Language: Английский

---