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Journal of Molecular Biology Aug 2021Cation-π interactions arise as a result of strong attractive forces between positively charged entities and the π-electron cloud of aromatic groups. The... (Review)
Review
Cation-π interactions arise as a result of strong attractive forces between positively charged entities and the π-electron cloud of aromatic groups. The physicochemical characteristics of cation-π interactions are particularly well-suited to the dual hydrophobic/hydrophilic environment of membrane proteins. As high-resolution structural data of membrane proteins bring molecular features into increasingly sharper view, cation-π interactions are gaining traction as essential contributors to membrane protein chemistry, function, and pharmacology. Here we review the physicochemical properties of cation-π interactions and present several prominent examples which demonstrate significant roles for this specialized biological chemistry.
Topics: Cations; Humans; Hydrogen Bonding; Hydrophobic and Hydrophilic Interactions; Membrane Proteins; Thermodynamics
PubMed: 33957146
DOI: 10.1016/j.jmb.2021.167035 -
Nucleic Acids Research Jun 2022The structure and properties of DNA depend on the environment, in particular the ion atmosphere. Here, we investigate how DNA twist -one of the central properties of...
The structure and properties of DNA depend on the environment, in particular the ion atmosphere. Here, we investigate how DNA twist -one of the central properties of DNA- changes with concentration and identity of the surrounding ions. To resolve how cations influence the twist, we combine single-molecule magnetic tweezer experiments and extensive all-atom molecular dynamics simulations. Two interconnected trends are observed for monovalent alkali and divalent alkaline earth cations. First, DNA twist increases monotonously with increasing concentration for all ions investigated. Second, for a given salt concentration, DNA twist strongly depends on cation identity. At 100 mM concentration, DNA twist increases as Na+ < K+ < Rb+ < Ba2+ < Li+ ≈ Cs+ < Sr2+ < Mg2+ < Ca2+. Our molecular dynamics simulations reveal that preferential binding of the cations to the DNA backbone or the nucleobases has opposing effects on DNA twist and provides the microscopic explanation of the observed ion specificity. However, the simulations also reveal shortcomings of existing force field parameters for Cs+ and Sr2+. The comprehensive view gained from our combined approach provides a foundation for understanding and predicting cation-induced structural changes both in nature and in DNA nanotechnology.
Topics: Cations; Cations, Divalent; Cations, Monovalent; DNA; Molecular Dynamics Simulation; Sodium; Sodium Chloride
PubMed: 35640616
DOI: 10.1093/nar/gkac445 -
International Journal of Molecular... Sep 2022The increasing concentration of CO in the atmosphere is related to global climate change. Carbon capture, utilization, and storage (CCUS) is an important technology to... (Review)
Review
The increasing concentration of CO in the atmosphere is related to global climate change. Carbon capture, utilization, and storage (CCUS) is an important technology to reduce CO emissions and to deal with global climate change. The development of new materials and technologies for efficient CO capture has received increasing attention among global researchers. Ionic liquids (ILs), especially functionalized ILs, with such unique properties as almost no vapor pressure, thermal- and chemical-stability, non-flammability, and tunable properties, have been used in CCUS with great interest. This paper focuses on the development of functionalized ILs for CO capture in the past decade (2012~2022). Functionalized ILs, or task-specific ILs, are ILs with active sites on cations or/and anions. The main contents include three parts: cation-functionalized ILs, anion-functionalized ILs, and cation-anion dual-functionalized ILs for CO capture. In addition, classification, structures, and synthesis of functionalized ILs are also summarized. Finally, future directions, concerns, and prospects for functionalized ILs in CCUS are discussed. This review is beneficial for researchers to obtain an overall understanding of CO-philic ILs. This work will open a door to develop novel IL-based solvents and materials for the capture and separation of other gases, such as SO, HS, NOx, NH, and so on.
Topics: Anions; Carbon; Carbon Dioxide; Cations; Ionic Liquids; Solvents
PubMed: 36232702
DOI: 10.3390/ijms231911401 -
Journal of Chromatography. A Aug 2022Members of the enterovirus genus are promising oncolytic agents. Their morphogenesis involves the generation of both genome-packed infectious capsids and empty capsids....
Members of the enterovirus genus are promising oncolytic agents. Their morphogenesis involves the generation of both genome-packed infectious capsids and empty capsids. The latter are typically considered as an impurity in need of removal from the final product. The separation of empty and full capsids can take place with centrifugation methods, which are of low throughput and poorly scalable, or scalable chromatographic processes, which typically require peak cutting and a significant trade-off between purity and yield. Here we demonstrate the application of packed bed cation exchange (CEX) column chromatography for the separation of empty capsids from infectious virions for a prototype strain of Coxsackievirus A21. This separation was developed using high throughput chromatography techniques and scaled up as a bind and elute polishing step. The separation was robust over a wide range of operating conditions and returned highly resolved empty and full capsids. The CEX step could be operated in bind and elute or flowthrough mode with similar selectivity and returned yields greater than 70% for full mature virus particles. Similar performance was also achieved using a selection of other bead based CEX chromatography media, demonstrating general applicability of this type of chromatography for Coxsackievirus A21 purification. These results highlight the wide applicability and excellent performance of CEX chromatography for the purification of enteroviruses, such as Coxsackievirus A21.
Topics: Antigens, Viral; Capsid; Cations; Chromatography, Ion Exchange; Enterovirus; Virion
PubMed: 35759911
DOI: 10.1016/j.chroma.2022.463259 -
Molecules (Basel, Switzerland) Sep 2022In this review, we discuss Friedel-Crafts-type aromatic amidation and acylation reactions, not exhaustively, but mainly based on our research results. The electrophilic... (Review)
Review
In this review, we discuss Friedel-Crafts-type aromatic amidation and acylation reactions, not exhaustively, but mainly based on our research results. The electrophilic species involved are isocyanate cation and acylium cation, respectively, and both have a common C=O structure, which can be generated from carboxylic acid functionalities in a strong Brønsted acid. Carbamates substituted with methyl salicylate can be easily ionized to the isocyanate cation upon (di)protonation of the salicylate. Carboxylic acids can be used directly as a source of acylium cations. However, aminocarboxylic acids are inert in acidic media because two positively charged sites, ammonium and acylium cation, will be generated, resulting in energetically unfavorable charge-charge repulsion. Nevertheless, the aromatic acylation of aminocarboxylic acids can be achieved by using tailored phosphoric acid esters as Lewis bases to abrogate the charge-charge repulsion. Both examples tame the superelectrophilic character.
Topics: Acids; Acylation; Ammonium Compounds; Carbamates; Carboxylic Acids; Cations; Isocyanates; Lewis Bases; Molecular Structure; Organophosphates; Salicylates
PubMed: 36144714
DOI: 10.3390/molecules27185984 -
The Journal of General Physiology Jul 2015The crystal structures of channels and transporters reveal the chemical nature of ion-binding sites and, thereby, constrain mechanistic models for their transport... (Review)
Review
The crystal structures of channels and transporters reveal the chemical nature of ion-binding sites and, thereby, constrain mechanistic models for their transport processes. However, these structures, in and of themselves, do not reveal equilibrium selectivity or transport preferences, which can be discerned only from various functional assays. In this Review, I explore the relationship between cation transport protein structures, equilibrium binding measurements, and ion transport selectivity. The primary focus is on K(+)-selective channels and nonselective cation channels because they have been extensively studied both functionally and structurally, but the principles discussed are relevant to other transport proteins and molecules.
Topics: Binding Sites; Cations; Crystallography, X-Ray; Ion Channel Gating; Ion Transport; Kinetics; Potassium Channels
PubMed: 26078056
DOI: 10.1085/jgp.201511371 -
Biochimica Et Biophysica Acta.... May 2021This review provides a retrospective on the role of osmotic regulation in the process of eukaryogenesis. Specifically, it focuses on the adjustments which must have been... (Review)
Review
This review provides a retrospective on the role of osmotic regulation in the process of eukaryogenesis. Specifically, it focuses on the adjustments which must have been made by the original colonizing α-proteobacteria that led to the evolution of modern mitochondria. We focus on the cations that are fundamentally involved in volume determination and cellular metabolism and define the transporter landscape in relation to these ions in mitochondria as we know today. We provide analysis on how the cations interplay and together maintain osmotic balance that allows for effective ATP synthesis in the organelle.
Topics: Animals; Cations; Evolution, Molecular; Humans; Ion Transport; Mitochondria; Osmoregulation
PubMed: 33422486
DOI: 10.1016/j.bbabio.2021.148368 -
Angewandte Chemie (International Ed. in... Oct 2016Catalysis by small molecules (≤1000 Da, 10(-9) m) that are capable of binding and activating substrates through attractive, noncovalent interactions has emerged... (Review)
Review
Catalysis by small molecules (≤1000 Da, 10(-9) m) that are capable of binding and activating substrates through attractive, noncovalent interactions has emerged as an important approach in organic and organometallic chemistry. While the canonical noncovalent interactions, including hydrogen bonding, ion pairing, and π stacking, have become mainstays of catalyst design, the cation-π interaction has been comparatively underutilized in this context since its discovery in the 1980s. However, like a hydrogen bond, the cation-π interaction exhibits a typical binding affinity of several kcal mol(-1) with substantial directionality. These properties render it attractive as a design element for the development of small-molecule catalysts, and in recent years, the catalysis community has begun to take advantage of these features, drawing inspiration from pioneering research in molecular recognition and structural biology. This Review surveys the burgeoning application of the cation-π interaction in catalysis.
Topics: Aminopyridines; Catalysis; Cations; Cycloaddition Reaction; Guanidine; Hydrogen Bonding; Lewis Acids; Quantum Theory; Small Molecule Libraries; Thiazoles
PubMed: 27329991
DOI: 10.1002/anie.201600547 -
Accounts of Chemical Research Apr 2013The chemistry community now recognizes the cation-π interaction as a major force for molecular recognition, joining the hydrophobic effect, the hydrogen bond, and the...
The chemistry community now recognizes the cation-π interaction as a major force for molecular recognition, joining the hydrophobic effect, the hydrogen bond, and the ion pair in determining macromolecular structure and drug-receptor interactions. This Account provides the author's perspective on the intellectual origins and fundamental nature of the cation-π interaction. Early studies on cyclophanes established that water-soluble, cationic molecules would forego aqueous solvation to enter a hydrophobic cavity if that cavity was lined with π systems. Important gas phase studies established the fundamental nature of the cation-π interaction. The strength of the cation-π interaction (Li(+) binds to benzene with 38 kcal/mol of binding energy; NH4(+) with 19 kcal/mol) distinguishes it from the weaker polar-π interactions observed in the benzene dimer or water-benzene complexes. In addition to the substantial intrinsic strength of the cation-π interaction in gas phase studies, the cation-π interaction remains energetically significant in aqueous media and under biological conditions. Many studies have shown that cation-π interactions can enhance binding energies by 2-5 kcal/mol, making them competitive with hydrogen bonds and ion pairs in drug-receptor and protein-protein interactions. As with other noncovalent interactions involving aromatic systems, the cation-π interaction includes a substantial electrostatic component. The six (four) C(δ-)-H(δ+) bond dipoles of a molecule like benzene (ethylene) combine to produce a region of negative electrostatic potential on the face of the π system. Simple electrostatics facilitate a natural attraction of cations to the surface. The trend for (gas phase) binding energies is Li(+) > Na(+) > K(+) > Rb(+): as the ion gets larger the charge is dispersed over a larger sphere and binding interactions weaken, a classical electrostatic effect. On other hand, polarizability does not define these interactions. Cyclohexane is more polarizable than benzene but a decidedly poorer cation binder. Many studies have documented cation-π interactions in protein structures, where lysine or arginine side chains interact with phenylalanine, tyrosine, or tryptophan. In addition, countless studies have established the importance of the cation-π interaction in a range of biological processes. Our work has focused on molecular neurobiology, and we have shown that neurotransmitters generally use a cation-π interaction to bind to their receptors. We have also shown that many drug-receptor interactions involve cation-π interactions. A cation-π interaction plays a critical role in the binding of nicotine to ACh receptors in the brain, an especially significant case. Other researchers have established important cation-π interactions in the recognition of the "histone code," in terpene biosynthesis, in chemical catalysis, and in many other systems.
Topics: Anions; Benzene; Carbon; Cations; Hydrogen; Hydrogen Bonding; Hydrophobic and Hydrophilic Interactions; Models, Molecular; Phenylalanine; Proteins; Static Electricity; Tryptophan; Water
PubMed: 23214924
DOI: 10.1021/ar300265y -
International Journal of Molecular... Jun 2020Membrane intrinsic transport systems play an important role in maintaining ion and pH homeostasis and forming the proton motive force in the cytoplasm and cell... (Review)
Review
Membrane intrinsic transport systems play an important role in maintaining ion and pH homeostasis and forming the proton motive force in the cytoplasm and cell organelles. In most organisms, cation/proton antiporters (CPAs) mediate the exchange of K, Na and Ca for H across the membrane in response to a variety of environmental stimuli. The tertiary structure of the ion selective filter and the regulatory domains of CPAs have been determined and a molecular mechanism of cation exchange has been proposed. Due to symbiogenesis, CPAs localized in mitochondria and chloroplasts of eukaryotic cells resemble prokaryotic CPAs. CPAs primarily contribute to keeping cytoplasmic Na concentrations low and controlling pH, which promotes the detoxification of electrophiles and formation of proton motive force across the membrane. CPAs in cyanobacteria and chloroplasts are regulators of photosynthesis and are essential for adaptation to high light or osmotic stress. CPAs in organellar membranes and in the plasma membrane also participate in various intracellular signal transduction pathways. This review discusses recent advances in our understanding of the role of CPAs in cyanobacteria and plant cells.
Topics: Antiporters; Bacteria; Biological Transport; Cations; Organelles; Photosynthesis; Plant Cells; Proton-Motive Force; Protons
PubMed: 32604959
DOI: 10.3390/ijms21124566