Specific ion binding by carboxylates (−COO–) is a broadly important topic because −COO– is one of the most common functional groups coordinated to metal ions in metalloproteins and synthetic ...polymers. We apply quantum chemical methods and the quasi-chemical free-energy theory to investigate how variations in the number of −COO– ligands in a binding site determine ion-binding preferences. We study a series of monovalent (Li+, Na+, K+, Cs+) and divalent (Zn2+, Ca2+) ions relevant to experimental work on ion channels and ionomers. Of two competing hypotheses, our results support the ligand field strength hypothesis and follow the reverse Hofmeister series for ion solvation and ion transfer from aqueous solution to binding sites with the preferred number of ligands. New insight arises from the finding that ion-binding sequences can be manipulated and even reversed just by constraining the number of carboxylate ligands in the binding sites. Our results help clarify the discrepancy in ion association between molecular ligands in aqueous solutions and ionomers, and their chemical analogues in ion-channel binding sites.
Molecular-level understanding and characterization of solvation environments are often needed across chemistry, biology, and engineering. Toward practical modeling of local solvation effects of any ...solute in any solvent, we report a static and all-quantum mechanics-based cluster-continuum approach for calculating single-ion solvation free energies. This approach uses a global optimization procedure to identify low-energy molecular clusters with different numbers of explicit solvent molecules and then employs the smooth overlap for atomic positions learning kernel to quantify the similarity between different low-energy solute environments. From these data, we use sketch maps, a nonlinear dimensionality reduction algorithm, to obtain a two-dimensional visual representation of the similarity between solute environments in differently sized microsolvated clusters. After testing this approach on different ions having charges 2+, 1+, 1–, and 2–, we find that the solvation environment around each ion can be seen to usually become more similar in hand with its calculated single-ion solvation free energy. Without needing either dynamics simulations or an a priori knowledge of local solvation structure of the ions, this approach can be used to calculate solvation free energies within 5% of experimental measurements for most cases, and it should be transferable for the study of other systems where dynamics simulations are not easily carried out.
Potassium channels modulate various cellular functions through efficient and selective conduction of K
+
ions. The mechanism of ion conduction in potassium channels has recently emerged as a topic of ...debate. Crystal structures of potassium channels show four K
+
ions bound to adjacent binding sites in the selectivity filter, while chemical intuition and molecular modeling suggest that the direct ion contacts are unstable. Molecular dynamics (MD) simulations have been instrumental in the study of conduction and gating mechanisms of ion channels. Based on MD simulations, two hypotheses have been proposed, in which the four-ion configuration is an artifact due to either averaged structures or low temperature in crystallographic experiments. The two hypotheses have been supported or challenged by different experiments. Here, MD simulations with polarizable force fields validated by
ab initio
calculations were used to investigate the ion binding thermodynamics. Contrary to previous beliefs, the four-ion configuration was predicted to be thermodynamically stable after accounting for the complex electrostatic interactions and dielectric screening. Polarization plays a critical role in the thermodynamic stabilities. As a result, the ion conduction likely operates through a simple single-vacancy and water-free mechanism. The simulations explained crystal structures, ion binding experiments and recent controversial mutagenesis experiments. This work provides a clear view of the mechanism underlying the efficient ion conduction and demonstrates the importance of polarization in ion channel simulations.
Polarization shapes the energy landscape of ion conduction in potassium channels.
The level of complexity with which any biological ion interaction mechanism can be investigated, whether it is a binding mechanism in proteins or a permeation mechanism in ion channels, is invariably ...limited by the state-of-the-art of our understanding of the characteristic properties of ion solvation. Currently, our understanding of the energetic properties of ion solvation in aqueous phase is considered adequate enough to have helped us obtain satisfactory descriptions of the role of energetics in several biological ion interaction processes. In contrast, the lack of consensus among all the experimental structural hydration data determined more than 10 years ago, particularly regarding ion hydration numbers, has limited us to nothing better than speculation regarding the roles of local spatial environments in these mechanisms. Here we revisit experimental and theoretical work applied to probe hydration numbers of three alkali metal ions, Li
+, Na
+ and K
+, and analyze them to clarify the current state-of-the-art of our understanding of their structural hydration properties. We find that with substantial improvements over the past 10 years in areas of experimental techniques, data analysis strategies, and theoretical and computational approaches for interrogating ion hydration structures, there is now growing consensus regarding the hydration numbers of these ions. We see that under physiological conditions,
ab initio methods suggest that all three ions prefer strong coordination with exactly 4 water molecules, a result we find consistent with some older experimental measurements.
Ab initio molecular dynamics (AIMD) simulations invariably identify additional “loosely” coordinated water molecules at the far slopes of the principle maxima of the radial distribution profiles for Na
+ and K
+ ions. We suggest that these statistical admixtures of additional oxygen atoms have resulted in the most recent experimentally determined hydration numbers of Na
+ ions to be 5 and K
+ ions to be 6.
Understanding the formation of H2CO3 in water from CO2 is important in environmental and industrial processes. Although numerous investigations have studied this reaction, the conversion of CO2 to ...H2CO3 in nanopores, and how it differs from that in bulk water, has not been understood. We use ReaxFF metadynamics molecular simulations to demonstrate striking differences in the free energy of CO2 conversion to H2CO3 in bulk and nanoconfined aqueous environments. We find that nanoconfinement not only reduces the energy barrier but also reverses the reaction from endothermic in bulk water to exothermic in nanoconfined water. Also, charged intermediates are observed more often under nanoconfinement than in bulk water. Stronger solvation and more favorable proton transfer with increasing nanoconfinement enhance the thermodynamics and kinetics of the reaction. Our results provide a detailed mechanistic understanding of an important step in the carbonation process, which depends intricately on confinement, surface chemistry, and CO2 concentration.
Transferring Na+ and K+ ions from their preferred coordination states in water to states having different coordination numbers incurs a free energy cost. In several examples in nature, however, these ...ions readily partition from aqueous-phase coordination states into spatial regions having much higher coordination numbers. Here we utilize statistical theory of solutions, quantum chemical simulations, classical mechanics simulations, and structural informatics to understand this aspect of ion partitioning. Our studies lead to the identification of a specific role of the solvation environment in driving transitions in ion coordination structures. Although ion solvation in liquid media is an exergonic reaction overall, we find it is also associated with considerable free energy penalties for extracting ligands from their solvation environments to form coordinated ion complexes. Reducing these penalties increases the stabilities of higher-order coordinations and brings down the energetic cost to partition ions from water into overcoordinated binding sites in biomolecules. These penalties can be lowered via a reduction in direct favorable interactions of the coordinating ligands with all atoms other than the ions themselves. A significant reduction in these penalties can, in fact, also drive up ion coordination preferences. Similarly, an increase in these penalties can lower ion coordination preferences, akin to a Hofmeister effect. Since such structural transitions are effected by the properties of the solvation phase, we anticipate that they will also occur for other ions. The influence of other factors, including ligand density, ligand chemistry, and temperature, on the stabilities of ion coordination structures are also explored.
Abstract
The limited flux and selectivities of current carbon dioxide membranes and the high costs associated with conventional absorption-based CO
2
sequestration call for alternative CO
2
...separation approaches. Here we describe an enzymatically active, ultra-thin, biomimetic membrane enabling CO
2
capture and separation under ambient pressure and temperature conditions. The membrane comprises a ~18-nm-thick close-packed array of 8 nm diameter hydrophilic pores that stabilize water by capillary condensation and precisely accommodate the metalloenzyme carbonic anhydrase (CA). CA catalyzes the rapid interconversion of CO
2
and water into carbonic acid. By minimizing diffusional constraints, stabilizing and concentrating CA within the nanopore array to a concentration 10× greater than achievable in solution, our enzymatic liquid membrane separates CO
2
at room temperature and atmospheric pressure at a rate of 2600 GPU with CO
2
/N
2
and CO
2
/H
2
selectivities as high as 788 and 1500, respectively, the highest combined flux and selectivity yet reported for ambient condition operation.
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