Water Wire Research Articles

Proton Transfer from a Photoacid to a Water Wire: First Principles Simulations and Fast Fluorescence Spectroscopy.

Proton transfer reactions are ubiquitous in chemistry, especially in aqueous solutions. We investigate photoinduced proton transfer between the photoacid 8-hydroxypyrene-1,3,6-trisulfonate (HPTS) and water using fast fluorescence spectroscopy and ab initio molecular dynamics simulations. Photoexcitation causes rapid proton release from the HPTS hydroxyl. Previous experiments on HPTS/water described the progress from photoexcitation to proton diffusion using kinetic equations with two time constants. The shortest time constant has been interpreted as protonated and photoexcited HPTS evolving into an "associated" state, where the proton is "shared" between the HPTS hydroxyl and an originally hydrogen bonded water. The longer time constant has been interpreted as indicating evolution to a "solvent separated" state where the shared proton undergoes long distance diffusion. In this work, we refine the previous experimental results using very pure HPTS. We then use excited state ab initio molecular dynamics to elucidate the detailed molecular mechanism of aqueous excited state proton transfer in HPTS. We find that the initial excitation results in rapid rearrangement of water, forming a strong hydrogen bonded network (a "water wire") around HPTS. HPTS then deprotonates in ≤3 ps, resulting in a proton that migrates back and forth along the wire before localizing on a single water molecule. We find a near linear relationship between the emission wavelength and proton-HPTS distance over the simulated time scale, suggesting that the emission wavelength can be used as a ruler for the proton distance. Our simulations reveal that the "associated" state corresponds to a water wire with a mobile proton and that the diffusion of the proton away from this water wire (to a generalized "solvent-separated" state) corresponds to the longest experimental time constant.

One hundred kilojoules of energy storage in water wire electric explosion deposition energy study

In this experiment, the electro-explosive deposition energy in water of aluminum-magnesium welding wire model ER5356 at 100 kJ capacitive storage energy was investigated. The loop current and the load discharge voltage during the wire electrical explosion were measured using a self-integrating Roche coil and a capacitive voltage divider, respectively. The physical process of electrical explosion and the energy deposition process were delineated by the measured loop currents and load voltages. The current waveform and load voltage of the electric explosion in water of 1.2 mm-3.0 mm diameter Al-Mg wire at 100 kJ stored energy were measured; the changes of load resistance value, load power and deposition energy of the wire loaded with electric explosion were calculated. The results show that the peak circuit current and peak time point decrease and then increase with increasing diameter, and the minimum value is achieved at 1.6 mm wire diameter; the load voltage and load resistance values gradually decrease with increasing diameter; the load power and total deposited energy of discharge achieve the maximum value at 2.0 mm diameter. At 100 kJ energy storage, there is an optimal range between 1.6 mm and 2.4 mm wire diameter.

Graph-Theory-Based Molecular Fragmentation for Efficient and Accurate Potential Surface Calculations in Multiple Dimensions.

We present a multitopology molecular fragmentation approach, based on graph theory, to calculate multidimensional potential energy surfaces in agreement with post-Hartree-Fock levels of theory but at the density functional theory cost. A molecular assembly is coarse-grained into a set of graph-theoretic nodes that are then connected with edges to represent a collection of locally interacting subsystems up to an arbitrary order. Each of the subsystems is treated at two levels of electronic structure theory, the result being used to construct many-body expansions that are embedded within an ONIOM scheme. These expansions converge rapidly with the many-body order (or graphical rank) of subsystems and capture many-body interactions accurately and efficiently. However, multiple graphs, and hence multiple fragmentation topologies, may be defined in molecular configuration space that may arise during conformational sampling or from reactive, bond breaking and bond formation, events. Obtaining the resultant potential surfaces is an exponential scaling proposition, given the number of electronic structure computations needed. We utilize a family of graph-theoretic representations within a variational scheme to obtain multidimensional potential surfaces at a reduced cost. The fast convergence of the graph-theoretic expansion with increasing order of many-body interactions alleviates the exponential scaling cost for computing potential surfaces, with the need to only use molecular fragments that contain a fewer number of quantum nuclear degrees of freedom compared to the full system. This is because the dimensionality of the conformational space sampled by the fragment subsystems is much smaller than the full molecular configurational space. Additionally, we also introduce a multidimensional clustering algorithm, based on physically defined criteria, to reduce the number of energy calculations by orders of magnitude. The molecular systems benchmarked include coupled proton motion in protonated water wires. The potential energy surfaces and multidimensional nuclear eigenstates obtained are shown to be in very good agreement with those from explicit post-Hartree-Fock calculations that become prohibitive as the number of quantum nuclear dimensions grows. The developments here provide a rigorous and efficient alternative to this important chemical physics problem.

Inhibition of aluminum chloride-induced amyloid Aβ peptide accumulation and brain neurodegeneration by Bougainvillea spectabilis flower decoction.

Objective(s): To investigate the potential therapeutic effect of Bougainvillea spectabilis flower decoction on aluminum chloride (AlCl3)-induced neurotoxicity. Materials and Methods:Rats received daily intraperitoneal injections of AlCl3 at 10 mg/kg for two months and were treated with B. spectabilis decoction at 50 or 100 mg/kg or saline during the 2nd month of the study. The control group received saline. Brain malondialdehyde (MDA), nitric oxide (NO), reduced glutathione (GSH), acetylcholinesterase (AChE), amyloid Aβ peptide, and interleukin-6 (IL-6) concentrations and paraoxonase-1 (PON-1) activity were determined and brain histology was done. Behavioral and neurological testing included Morris water maze (WMZ), Y maze, and wire hanging. Results:Compared with saline controls, AlCl3 significantly increased brain MDA and NO along with decreased GSH and PON-1 activity. It also increased AChE, IL-6, and amyloid Aβ concentrations. AlCl3 impaired motor strength and memory performance and caused brain neurodegeneration. B. spectabilis decoction given at 50 or 100 mg/kg protected against the biochemical and histopathological alterations evoked by AlCl3 by alleviating the increase in MDA and NO, and decrease in GSH and PON-1 activity. B. spectabilis decoction showed no significant effect on AChE but markedly decreased IL-6 and amyloid Aβ in the brain of AlCl3-treated rats. It also restored memory performance and motor strength, and protected against AlCl3-induced neurodegeneration.Conclusion:These results suggest that B. spectabilis flower decoction might prove of value in the treatment of Alzheimer’s disease.

Pore-Scale Simulation of the Interaction between a Single Water Droplet and a Hydrophobic Wire Mesh Screen in Diesel

Recently, the trend towards sustainable energy production and pollution control has motivated the increased consumption of ultra-low-sulfur diesel (ULSD) or bio-fuels. Such fuels have relatively low surface tension with water and therefore, the separation of water from fuel has become a challenging problem. The separation process relies on using porous structures for the collection and removal of water droplets. Hence, understanding the interaction between water droplets and the separators is vital. The simplest geometry of a separator is the wire mesh screen, which is used in many modern water–diesel separators. Thus, it is considered here for systematic study. In this work, pore-scale computational fluid dynamics (CFD) simulations were performed using OpenFOAM® (an open-source C++ toolbox for fluid dynamics simulations) coupled with a new accurate scheme for the computation of the surface tension force. First, two validation test cases were performed and compared to experimental observations in corresponding bubble-point tests. Second, in order to describe the interaction between water droplets and wire mesh screens, the simulations were performed with different parameters: mean diesel velocity, open area ratio, fiber radii, Young–Laplace contact angle, and the droplet radius. New correlations were obtained which describe the average reduction of open surface area (clogging), the pressure drop, and retention criteria.

Identification of a Grotthuss proton hopping mechanism at protonated polyhedral oligomeric silsesquioxane (POSS) – water interface

The attachment and dissociation of a proton from a water molecule and the proton transfers at solid–liquid interfaces play vital roles in numerous biological, chemical processes and for the development of sustainable functional materials for energy harvesting and conversion applications. Using first-principles computational methodologies, we investigated the protonated forms of polyhedral oligomeric silsesquioxane (POSS-H+) interacting with water clusters (Wn, where n = 1–6) as a model to quantify the proton conducting and localization ability at solid–liquid interfaces. Successive addition of explicit water molecules to POSS-H+ shows that the assistance of at least three water molecules is required to dissociate the proton from POSS with the formation of an Eigen cation (H9O4+), whereas the presence of a fourth water molecule highly favors the formation of a Zundel ion (H5O2+). Reaction pathway and energy barrier analysis reveal that the formation of the Eigen cation requires significantly higher energy than the Zundel features. This confirms that the Zundel ion is destabilized and promptly converts in to Eigen ion at this interface. Moreover, we identified a Grotthuss-type mechanism for the proton transfer through a water chain close to the interface, where symmetrical and unsymmetrical arrangements of water molecules around H+ of protonated POSS-H+ are involved in the conduction of proton through water wires where successive Eigen-to-Zundel and Zundel-to-Eigen transformations are observed in quick succession.

Theoretical Insights into Excited-State Intermolecular Proton Transfers of 2,7-Diazaindole in Water Using a Microsolvation Approach.

The detailed excited-state intermolecular proton transfer (ESInterPT) mechanism of 2,7-diazaindole with water wires consisting of either one or two shells [2,7-DAI(H2O)n; n = 1-5] has been theoretically explored by time-dependent density functional theory using microsolvation with an implicit solvent model. On the basis of the excited-state potential energy surfaces along the proton transfer (PT) coordinates, among all 2,7-DAI(H2O)n, the multiple ESInterPT of 2,7-DAI(H2O)2+3 through the first hydration shell (inner circuit) is the most easy process to occur with the lowest PT barrier and a highly exothermic reaction. The lowest PT barrier resulted from the outer three waters pushing the inner circuit waters to be much closer to 2,7-DAI, leading to the enhanced intermolecular hydrogen-bonding strength of the inner two waters. Moreover, on-the-fly dynamic simulations show that the multiple ESInterPT mechanism of 2,7-DAI(H2O)2+3 is the triple PT in a stepwise mechanism with the highest PT probability. This solvation effect using microsolvation and dynamic simulation is a cost-effect approach to reveal the solvent-assisted multiple proton relay of chromophores based on excited-state proton transfer.

Structural Basis for the Function of the C-Terminal Proton Release Pathway in the Calcium Pump.

The calcium pump (sarco/endoplasmic reticulum Ca2+-ATPase, SERCA) plays a major role in calcium homeostasis in muscle cells by clearing cytosolic Ca2+ during muscle relaxation. Active Ca2+ transport by SERCA involves the structural transition from a low-Ca2+ affinity E2 state toward a high-Ca2+ affinity E1 state of the pump. This structural transition is accompanied by the countertransport of protons to stabilize the negative charge and maintain the structural integrity of the transport sites and partially compensate for the positive charges of the two Ca2+ ions passing through the membrane. X-ray crystallography studies have suggested that a hydrated pore located at the C-terminal domain of SERCA serves as a conduit for proton countertransport, but the existence and function of this pathway have not yet been fully characterized. We used atomistic simulations to demonstrate that in the protonated E2 state and the absence of initially bound water molecules, the C-terminal pore becomes hydrated in the nanosecond timescale. Hydration of the C-terminal pore is accompanied by the formation of water wires that connect the transport sites with the cytosol. Water wires are known as ubiquitous proton-transport devices in biological systems, thus supporting the notion that the C-terminal domain serves as a conduit for proton release. Additional simulations showed that the release of a single proton from the transport sites induces bending of transmembrane helix M5 and the interaction between residues Arg762 and Ser915. These structural changes create a physical barrier against full hydration of the pore and prevent the formation of hydrogen-bonded water wires once proton transport has occurred through this pore. Together, these findings support the notion that the C-terminal proton release pathway is a functional element of SERCA and also provide a mechanistic model for its operation in the catalytic cycle of the pump.

Proton-Coupled Electron Transfer in the Aqueous Nanochannels of Lyotropic Liquid Crystals: Interplay of H-Bonding and Polarity Effects.

A molecular-level description of the aqueous nanochannels in lyotropic liquid crystals (LLCs) is crucial for their widespread utilization in diverse fields. Herein, the polarity and hydrogen bonding effects of LLC water molecules have been simultaneously explored using a single probe, 4'-N,N-dimethylamino-3-hydroxyflavone (DMA3HF), by the unique multiparametric sensitivity of the excited state proton-coupled electron transfer (PCET) phenomenon. The decreased ESIPT efficiency and the significantly retarded ESIPT dynamics (>20 times) of DMA3HF in the LLC phases suggests the dominant influence of strong hydrogen-bonded solute-solvent complexes that leads to a high activation barrier for ESIPT in the mesophases. The effects of hydrogen bonding on ESIPT have been elucidated by enhanced sampling techniques based on classical MD simulations of DMA3HF in explicit water. ESIPT via an extended hydrogen-bonded water wire is associated with a significantly high ESIPT activation barrier, substantiating the experimentally observed slow ESIPT dynamics inside the LLCs.

Two Faces of Water in the Formation and Stabilization of Multicomponent Crystals of Zwitterionic Drug-Like Compounds

Two new hydrated multicomponent crystals of zwitterionic 2-aminonicotinic acid with maleic and fumaric acids have been obtained and thoroughly characterized by a variety of experimental (X-ray analysis and terahertz Raman spectroscopy) and theoretical periodic density functional theory calculations, followed by Bader analysis of the crystalline electron density) techniques. It has been found that the Raman-active band in the region of 300 cm−1 is due to the vibrations of the intramolecular O-H...O bond in the maleate anion. The energy/enthalpy of the intermolecular hydrogen bonds was estimated by several empirical approaches. An analysis of the interaction networks reflects the structure-directing role of the water molecule in the examined multicomponent crystals. A general scheme has been proposed to explain the proton transfer between the components during the formation of multicomponent crystals in water. Water molecules were found to play the key role in this process, forming a “water wire” between the COOH group of the dicarboxylic acid and the COO– group of the zwitterion and the rendering crystal lattice of the considered multicomponent crystals.

Hydroxy Channels-Adaptive Pathways for Selective Water Cluster Permeation.

Artificial water channels (AWCs) are known to selectively transport water, with ion exclusion. Similarly to natural porins, AWCs encapsulate water wires or clusters, offering continuous and iterative H-bonding that plays a vital role in their stabilization. Herein, we report octyl-ureido-polyol AWCs capable of self-assembly into hydrophilic hydroxy channels. Variants of ethanol, propanediol, and trimethanol are used as head groups to modulate the water transport permeabilities, with rejection of ions. The hydroxy channels achieve a single-channel permeability of 2.33 × 108 water molecules per second, which is within the same order of magnitude as the transport rates for aquaporins. Depending on their concentration in the membrane, adaptive channels are observed in the membrane. Over increased concentrations, a significant shift occurs, initiating unexpected higher water permeation. Molecular simulations probe that spongelike or cylindrical aggregates can form to generate transient cluster water pathways through the bilayer. Altogether, the adaptive self-assembly is a key feature influencing channel efficiency. The adaptive channels described here may be considered an important milestone contributing to the systematic discovery of artificial water channels for water desalination.

Exploring the Proton-Transfer Mechanism in Hv1 by Multi-Scale Simulations

The Hv1 proton channel is expressed in a broad range of eukaryotic cells, where its chief physiological role is to mediate proton efflux. Hv1 is a potential target for the development of drugs to treat human pathologies, including breast cancer and ischemic stroke. Similar to other voltage sensor (VS) domain-containing proteins, Hv1 gating is controlled by changes in membrane potential. The H+ permeation pathway in Hv1 is formed by an hourglass-shaped hydrated VS central crevice, with several conserved hydrophobic residues forming a central bottleneck region. Although specific residues have been identified as potential sites for proton transfer by explicit side chain ionization, almost all neutralizations of ‘selectivity filter’ residues D112, R211, and other highly conserved ‘gating-charge’ or ‘counter-charge’ residues have so far failed to abolish H+ currents on Hv1. An alternative H+ transfer mechanism, in which VS-resident water molecules form a water wire, has not been ruled out. To investigate structural constraints on possible water wire formation in Hv1 we conducted classical molecular dynamics simulations followed by mixed quantum-mechanics/molecular-mechanics (QM/MM) simulations on a new, experimentally constrained activated-state Hv1 model structure. The calculations will allow us to focus on how dynamics in the bottleneck region that envelops a D112-R211 salt bridge impact water and side chain hydrogen bond network structures, possible water wire formation, and energetic barriers to proton migration.

A Step-by-Step Process-Induced Unidirectional Oriented Water Wire in the Nanotube.

The orientation of water molecules is a key requirement for the fast transport of water in nanotubes. It has been accepted that the flip of the water chain follows a concerted mechanism, which has led to the view that bidirectional water flux in nanotubes can be transformed into unidirectional transport when the orientation of water molecules is maintained in long nanotubes under the external field. In this Letter, on the basis of molecular dynamics simulations and first-principles calculations, we confirmed that the flip of the water chain is a step-by-step process, which is different from the perceived concerted mechanism. Further analysis indicated that without an external field, it needed more than 20 water molecules to maintain the unidirectional single-file water flow in a carbon nanotube at a duration time of seconds. Considering that the thickness of the cell membrane (normally 5-10 nm) is larger than the length threshold of the unidirectional water wire, this study suggested that it may not require the external field to maintain the unidirectional flow in the water channel at the macroscopic time scale.

Functional Water Wires Catalyze Long-Range Proton Pumping in the Mammalian Respiratory Complex I.

The respiratory complex I is a gigantic (1 MDa) redox-driven proton pump that reduces the ubiquinone pool and generates proton motive force to power ATP synthesis in mitochondria. Despite resolved molecular structures and biochemical characterization of the enzyme from multiple organisms, its long-range (∼300 Å) proton-coupled electron transfer (PCET) mechanism remains unsolved. We employ here microsecond molecular dynamics simulations to probe the dynamics of the mammalian complex I in combination with hybrid quantum/classical (QM/MM) free energy calculations to explore how proton pumping reactions are triggered within its 200 Å wide membrane domain. Our simulations predict extensive hydration dynamics of the antiporter-like subunits in complex I that enable lateral proton transfer reactions on a microsecond time scale. We further show how the coupling between conserved ion pairs and charged residues modulate the proton transfer dynamics, and how transmembrane helices and gating residues control the hydration process. Our findings suggest that the mammalian complex I pumps protons by tightly linked conformational and electrostatic coupling principles.

DpgC-Catalyzed Peroxidation of 3,5-Dihydroxyphenylacetyl-CoA (DPA-CoA): Insights into the Spin-Forbidden Transition and Charge Transfer Mechanisms*.

Despite being a very strong oxidizing agent, most organic molecules are not oxidized in the presence of O2 at room temperature because O2 is a diradical whereas most organic molecules are closed-shell. Oxidation then requires a change in the spin state of the system, which is forbidden according to non-relativistic quantum theory. To overcome this limitation, oxygenases usually rely on metal or redox cofactors to catalyze the incorporation of, at least, one oxygen atom into an organic substrate. However, some oxygenases do not require any cofactor, and the detailed mechanism followed by these enzymes remains elusive. To fill this gap, here the mechanism for the enzymatic cofactor-independent oxidation of 3,5-dihydroxyphenylacetyl-CoA (DPA-CoA) is studied by combining multireference calculations on a model system with QM/MM calculations. Our results reveal that intersystem crossing takes place without requiring the previous protonation of molecular oxygen. The characterization of the electronic states reveals that electron transfer is concomitant with the triplet-singlet transition. The enzyme plays a passive role in promoting the intersystem crossing, although spontaneous reorganization of the water wire connecting the active site with the bulk presets the substrate for subsequent chemical transformations. The results show that the stabilization of the singlet radical-pair between dioxygen and enolate is enough to promote spin-forbidden reaction without the need for neither metal cofactors nor basic residues in the active site.

Small molecule crystals with 1D water wires modulate electronic properties of surface water networks

This study evaluates the effect of water vapor pressure on the surface conductivity of a hydrated small molecule crystal under dry and wet conditions. The crystal contains a discrete metal complex with waters of hydration in structural positions and in 1D water wires. Under dry conditions, the surface of the hydrated crystal behaves as a near ideal capacitor. Under wet conditions, the waters of hydration serve as a template to assemble surface water networks by organization of water from the environment. The surface water provides pathways for charge transfer attributed to proton mobility that increases conductivity by > 3 orders in magnitude. Modulation between wet and dry conditions tunes the conductivity of the crystal surface via a two-step process, which has been evaluated kinetically as a function of the water vapor pressure.

Perfection of the equipment of electromagnetic stirring in moulds of billet and bloom CCM

To avoid defects of continuously casted billets, such as core porosity, shrink liquation, ingot developed dendrite structure and others, various methods of external physical impact on the crystallizing billet are used. One of the most technological and effective of them is the electromagnetic stirring (EMS) of the liquid melt of the crystallizing billet. An analysis of the experience of industrial EMS systems application at steel plants of Russia was accomplished. It was noted, that operating in Russia industrial CCM, intended for production of high quality billets, are equipped mainly by EMS systems of foreign production. The stator of the EMS is located outside a mould body and the bodies of the stator and the mould are manufactured of nonmagnetic steel of austenite class. Such systems are characterized by low reliability and high energy consumption because of their design features (location outside a mould body and necessity to use for them a separate circuit of cooling by a “boiler” water). Bessides, most of the EMS stators of foreign manufacturing are made in nonseparable bodies, hence in case of a failure the expensive rrepair of the stators should be carried out at the foreign plants-manufacturers. At present in Russia the EMS systems are being elaboorrated by specialists of AKKH “VNIIMETMASH”, Moscow. VNIIMETMASH within the frame of import substitution program elaboorated both built-in and external variants of EMS systems for moulds of billet and bloom CCM, the stator coil poles being cooled bby the water of the mould and its winding is made of immersible into water wire with a double insulation. Based on the results of thee study it was determined, that location of the elaborated EMS systems in a mould results in improving of the surface quality, as welll as quality of the subsurface layer and the billet macro-structure, decreasing of the point unevenness and decreasing of number of thee subshell bubbles.

Characterizing the water wire in the Gramicidin channel found by Monte Carlo sampling using continuum electrostatics and in molecular dynamics trajectories with conventional or polarizable force fields

Water molecules play a key role in all biochemical processes. They help define the shape of proteins, and they are reactant or product in many reactions and are released as ligands are bound. They facilitate the transfer of protons through transmembrane proton channel, pump and transporter proteins. Continuum electrostatics (CE) force fields used by program Multiconformation CE (MCCE) capture electrostatic interactions in biomolecules with an implicit solvent, which captures the averaged solvent water equilibrium properties. Hybrid CE methods can use explicit water molecules within the protein surrounded by implicit solvent. These hybrid methods permit the study of explicit hydrogen bond networks within the protein and allow analysis of processes such as proton transfer reactions. Yet hybrid CE methods have not been rigorously tested. Here, we present an explicit treatment of water molecules in the Gramicidin A (gA) channel using MCCE and compare the resulting distributions of water molecules and key hydration features against those obtained with explicit solvent Molecular Dynamics (MD) simulations with the nonpolarizable CHARMM36 and polarizable Drude force fields. CHARMM36 leads to an aligned water wire in the channel characterized by a large absolute net water dipole moment; the MCCE and Drude analysis lead to a small net dipole moment as the water molecules change orientation within the channel. The correct orientation is not as yet known, so these calculations identify an open question.

Characterizing the Water Wire in the Gramicidin Channel Found by Monte Carlo Sampling Using Continuum Electrostatics and in Molecular Dynamics Trajectories with Conventional or Polarizable Force Fields

Water molecules play a key role in all biochemical processes. They help define the shape of proteins, and they are reactant or product in many reactions and are released as ligands are bound. They facilitate the transfer of protons through transmembrane proton channel, pump and transporter proteins. Continuum electrostatics (CE) force fields used by program Multiconformation CE (MCCE) capture electrostatic interactions in biomolecules with an implicit solvent, which captures the averaged solvent water equilibrium properties. Hybrid CE methods can use explicit water molecules within the protein surrounded by implicit solvent. These hybrid methods permit the study of explicit hydrogen bond networks within the protein and allow analysis of processes such as proton transfer reactions. Yet hybrid CE methods have not been rigorously tested. Here, we present an explicit treatment of water molecules in the Gramicidin A (gA) channel using MCCE and compare the resulting distributions of water molecules and key hydration features against those obtained with explicit solvent Molecular Dynamics (MD) simulations with the nonpolarizable CHARMM36 and polarizable Drude force fields. CHARMM36 leads to an aligned water wire in the channel characterized by a large absolute net water dipole moment; the MCCE and Drude analysis lead to a small net dipole moment as the water molecules change orientation within the channel. The correct orientation is not as yet known, so these calculations identify an open question.

Water-Assisted Proton Transport in Confined Nanochannels

Hydrated excess protons under hydrophobic confinement are a critical component of charge transport behavior and reactivity in nanoporous materials and biomolecular systems. Herein, excess proton confinement effects are computationally investigated for sub-2 nm hydrophobic nanopores by varying the diameters (d = 0.81, 0.95, 1.09, 1.22, 1.36, 1.63, and 1.90 nm), lengths (l ∼3 and ∼5 nm), curvature, and chirality of cylindrical carbon nanotube (CNT) nanopores. CNTs with a combination of different diameter segments are also explored. The spatial distribution of water molecules under confinement is diameter-dependent; however, proton solvation and transport are consistently found to occur in the water layer adjacent to the pore wall, showing an “amphiphilic” character of the hydrated excess proton hydronium-like structure. The proton transport free energy barrier also decreases significantly as the nanopore diameter increases and proton transport becomes almost barrierless in the d > 1 nm nanopores. Among the nanopores studied, the Zundel cation (H5O2+) is populated only in the d = 0.95 nm CNT (7,7) nanopore. The presence of the hydrated excess proton and K+ inside the CNT (7,7) nanopore induces a water density increase by 40 and 20%, respectively. The K+ transport through CNT nanopores is also consistently higher in the free energy barrier than proton transport. Interestingly, the evolution of excess protonic charge defect distribution reveals a “frozen” single water wire configuration in the d = 0.81 nm CNT (6,6) nanopore (or segment), through which hydrated excess protons can only shuttle via the Grotthuss mechanism. Vehicular diffusion becomes relevant to proton transport in the “flat” free energy regions and in the wider nanopores, where protons do not primarily shuttle in the axial direction.