Selbstorganisierte künstliche Ionenkanäle für die natürliche Selektion von Funktionen

Abstract

Aufgrund ihrer wichtigen physiologischen Funktionen, insbesondere als selektive Relais für die Translokation physiologisch relevanter Spezies durch Zellmembranen, spielen natürliche Ionenkanäle eine wichtige Rolle in lebenden Organismen. In den letzten Jahrzehnten hat sich das Gebiet der selbstorganisierten Ionenkanäle kontinuierlich weiterentwickelt. Für die Synthese unimolekularer Kanäle oder nichtkovalent selbstorganisierter Kanäle, die zum Nachahmen natürlicher Ionenkanalproteine ausgelegt sind und für die vielfältige, sich ineinander umwandelnde oder adaptive Kanalleitungszustände beobachtet werden können, wurden konvergente mehrdimensionale Selbstorganisationsstrategien verwendet. In diesem Aufsatz geben wir eine Übersicht über die Entwicklung verschiedener selbstorganisierter künstlicher Kanäle, insbesondere ihren Aufbau, das Selbstorganisationsverhalten, die Transportaktivität in Lipiddoppelschichtmembranen, Transportmechanismen, und stellen Vergleiche mit natürlichen Ionenkanälen an. Wir diskutieren die Anwendungen künstlicher Ionenkanäle sowie mögliche Probleme, die das Gebiet erwarten, und zukünftige Entwicklungen.

Biomimetic Approach for Highly Selective Artificial Water Channels Based on Tubular Pillar[5]arene Dimers

“…Green CHCl 3 molecules in CPK representation are perfectly positioning aClatom fitting the narrowest carboxy-phenyl pore, while the other atoms are disordered in the larger junction formed via hydrogen bonding of the carboxylate groups. Herein we concentrate our efforts on investigation of water/ion transport abilities of self-assembled discrete tubular dimers of rim-differentiated peralkyl-carboxylate-pillar- [5]arenes PA D4, PA D8 and PA D12 ( Figure 1a)t hrough bilayer lipid membrane.I nterestingly,t he analysis of x-ray single structure of PA D4 show that two dimeric tubular architectures.Itresults in the formation of tubular carboxylic dimers pS-pS and pR-pR and of bilayer dimers form via two different H-bonding vs.h ydrophobic binding modes,r espectively ( Figure 1b,r ed). The1 5h ydrogen bonds between the carboxyl groups and water molecules and adopts closely spaced carboxy-phenyl groups with af ivefold helical conformation, [29] which in turn superpose the pillar [5]arene relay of 5 diameter with anarrowest twisted hydrophobic pore of 2.8 diameter (Figure 1c).…”

“…Overall, the PA D4, PA D8 and PA D12 dimers,o btained using simple chemistry,can be assembled into highly selective artificial water channels and remain stable in lipid membranes.P reviously,t he seminal discovery of pillar [5]arene PA Pu nimolecular channels by Hou et al [15] are at long last beginning to meet encouraging signs for high water permeability (10 6 -10 8 water molecules/second/channel), while most of these channels present ionic transport activity,thus not yet selectivity.N atural AQPc hannels present an hourglass structure offering size SF restriction of % 3 and selectivity against cations,r einforced through electrostatic repulsion in the region known as the aromatic arginine (ar/R) constriction. [2b] In this study as imple serendipitous modification of rims of pillar [5]arene backbone of 5 diameter led to the construction of asupplementary narrowest hydrophobic pore of 2.6-2.8 diameter within the same structure,a ffording asize restriction control of translocation along tubular dimers at this selectivity filter level. Thewater permeability of PA D4, PA D8 and PA D12 channels ( % 10 7 water molecules s À1 /channel) is only one orders of magnitude lower than that of AQPs, and more important they are rejecting alkali cations.D ifferently to previous selective I-quartets where water molecules are interacting along the whole structure of the channel of % 2.8 ,herein the narrowest pore structure of PA D4, PA D8 and PA D12 channels in precisely located at the two narrowest regions of the pore,w hich remains larger along the resting length of the pore.The narrowest diameter of the pore itself is large enough for the water molecules to pass having themselves ad iameter of % 2.8 ,b ut restrictive enough to block the passage of hydrated Na + or K + cations.…”

“…[9] We know that apore with adiameter of % 3 is acritical prerequisite to selectively accommodate and transport waterwires. [27] Pillar [5]arene platform presents ah ydrophobic cavity of 5 diameter, which in turn is much bigger to selectively accommodate single water-wires. [12,29] Having an inner pore size of % 5 ,t hey allow the passage of cations according to their hydration energy.…”

“…a) Structures of peralkylcarboxylate-pillar [5]arenes PAD4, PAD8 and PAD12 and b) X-ray single crystal structure of PAD4. [29] Crystal packing along c-axis emphasizing self-assembled a) tubular carboxylate H-bonding (red) and b) bilayer hydrophobic (blue) dimers in stick and CPK representations Crystalline solid state structures show dimeric structures of 34 length and c) avariable pore geometry composed of Pillar [5]arene platform (blue) of 5 diameter and of narrowest twisted carboxy-phenyl pore of 2.8 diameter (red). Green CHCl 3 molecules in CPK representation are perfectly positioning aClatom fitting the narrowest carboxy-phenyl pore, while the other atoms are disordered in the larger junction formed via hydrogen bonding of the carboxylate groups.…”

Biomimetic Approach for Highly Selective Artificial Water Channels Based on Tubular Pillar[5]arene Dimers

“…Herein we concentrate our efforts on investigation of water/ion transport abilities of self-assembled discrete tubular dimers of rim-differentiated peralkyl-carboxylate-pillar- [5]arenes PA D4, PA D8 and PA D12 ( Figure 1a)t hrough bilayer lipid membrane.I nterestingly,t he analysis of x-ray single structure of PA D4 show that two dimeric tubular architectures.Itresults in the formation of tubular carboxylic dimers pS-pS and pR-pR and of bilayer dimers form via two different H-bonding vs.h ydrophobic binding modes,r espectively ( Figure 1b,r ed). The1 5h ydrogen bonds between the carboxyl groups and water molecules and adopts closely spaced carboxy-phenyl groups with af ivefold helical conformation, [29] which in turn superpose the pillar [5]arene relay of 5 diameter with anarrowest twisted hydrophobic pore of 2.8 diameter (Figure 1c). This affords as ize restricted control of translocation along tubular channels at narrowest selectivity filter level, offering size restriction.…”