Ionic Block Research Articles

Synthesis of 1,2,4-triazolium salt-based polymers and block copolymers by RAFT polymerization: Ion conductivity and assembled structures

Well-defined 1,2,4-triazolium-based polymers were synthesized by reversible addition–fragmentation chain transfer (RAFT) polymerization of N-vinyl-1,2,4-triazolium salts, i.e., N-vinyl-4-ethyl-1,2,4-triazolium bromide (NVETri-Br) and N-vinyl-(4-ethoxyethyl)-1,2,4-triazolium bromide (NVEtOETri-Br). Reasonable control of the polymerization of these monomers was attained using a trithiocarbonate-type chain transfer agent (CTA), producing poly(N-vinyl-1,2,4-triazolium bromide)s with controlled molecular weights (Mn,SEC > 20000) and low Ð values (Mw/Mn < 1.1). Nonionic (water-soluble)-ionic (solubility tunable) block copolymers were achieved by RAFT polymerization of N-vinyl-1,2,4-triazolium salts using hydrophilic macro-CTAs derived from N-vinyl pyrrolidone (NVP) and N-vinyl-1,2,4-triazole (NVTri). The anion exchange reaction of the poly(NVETri-Br) segment in the block copolymers with lithium bis(trifluoromethanesulfonyl)imide (LiNTf2) proceeded selectively to afford amphiphilic block copolymers composed of hydrophobic poly(NVETri-NTf2) and hydrophilic nonionic segment, poly(NVP) or poly(NVTri). The ionic conductivity of poly(NVP)33-b-poly(NVETri-NTf2)67 was 4.3 × 10−5 S/cm at 25 °C, which was remarkably higher than that of poly(NVETri-NTf2) (1.7 × 10−5 S/cm). At 90 °C, poly(NVP)-b-poly(NVETri-NTf2) exhibited high ionic conductivities of 3.1–2.3 × 10−4 S/cm under the ambient humidity conditions, depending on the comonomer composition (NVP content = 12–33%). We believe that this represents the first report on controlled synthesis of 1,2,4-triazolium-based polymers and block copolymers that exhibit high characteristic ion-conducting properties, depending on the structure of the substituent group, counter anion, comonomer structure, and composition.

Stable 2D-structured supports incorporating ionic block copolymer-wrapped carbon nanotubes with graphene oxide toward compact decoration of metal nanoparticles and high-performance nano-catalysis

The incorporation of pyrene-functionalized poly(methyl methacrylate)-b-poly(dimethylaminoethyl methacrylate) (PMMA-b-PDMAEMA) ionic block copolymer-wrapped carbon nanotubes (PBCNTs) with graphene oxide (GO) allows compact decoration of metal nanoparticles (NP) for use as robust catalysts. This well-tailored concept of the PBCNT-GO functional carbon support provides various features, including a two-dimensional (2D) structure, dimensional stability, versatile solubility (from toluene to water), enhanced diffusion of reagents, and recyclability. Among the various compositions of GO and PBCNT, 50 wt% of the PBCNT additive-containing support (PBCGO55) showed great hybridization potential for Ag, Au, and Pd NPs. In particular, the hybridization of PBCGO55 with Pd NPs (Pd-PBCGO55) displayed superior morphological features with compact decoration of ultra-fine NPs (1–3 nm), larger surface area, higher density of edge and corner atoms, better dispersion stability, and lesser aggregation of the decorated Pd NPs in comparison with the other hybrid catalysts. In the catalytic reduction of 4-nitrophenol (4-NP), the Pd-PBCGO55 hybrid catalyst exhibited the best catalytic performance, resulting in highly enhanced reaction rate constant (k) of 9.73 min−1 and catalytic activity of 141.8 mol mol−1 min−1, exhibiting a 50-fold increased rate constant and 30-fold increased catalytic activity in comparison to Ag-GO without PBCNT (k = 0.19 min−1, catalytic activity = 4.58 mol mol−1 min−1).

Temperature and anion responsive self-assembly of ionic liquid block copolymers coating gold nanoparticles

In this paper, double hydrophilic ionic liquid block copolymers (ILBCs), poly poly[1-methyl-3-(2-methacryloyloxy propylimidazolium bromine)]-block-(N-isopropylacrylamide) (PMMPImB-b-PNIPAAm) was first synthesized by reversible additionfragmentation chain transfer (RAFT) and then attached on the surface of gold nanoparticles (Au NPs) via a strong gold-sulfur bonding for preparing hybrid nanoparticles (PMMPImB-b-PNIPAAm-@-Au NPs). The hybrid NPs had a three layers micelle-like structure, including a gold core, thermo-responsive inner shell and anion responsive outer corona. The self-assembling behavior of thermal- and anion-response from shell and corona were respectively investigated by change of temperature and addition of (CF3SO2)2N−. The results showed the hybrid NPs retained a stable dispersion beyond the lower critical solution temperature (LCST) because of the space or electrostatic protecting by outer PMMPImB. However, with increasing concentration of (CF3SO2)2N−, the micellization of self-assembling PMMPImB-b-PNIPAAm-@-Au NPs was induced to form micellar structure containing the core with hydrophobic PMMPImB-(CF3SO2)2N− surrounded by composite shell of Au NPs-PNIPAAm via the anionresponsive properties of ILBCs. These results indicated that the block copolymers protected plasmonic nanoparticles remain self-assembling properties of block copolymers when phase transition from outer corona polymer.

Development of Ionic Liquid-Tagged Carbohydrate Building Block for Electrochemical Glycosylation

Recently we have developed an electrochemical method for oligosaccharide synthesis based on the automated electrochemical assembly (AEA) of carbohydrate building blocks. This method enables us to access fully protected oligosaccharides rapidly in a preparative scale; however, the assembly of building blocks is one of the steps of oligosaccharide synthesis. In order to increase efficiency of the entire process, it is important to introduce a strategy which facilitates separation and purification of oligosaccharides thus-obtained. Separation tags are small molecules which are covalently attached to the substrates to make the separation step easier and faster. There are several tags including a fluorous tag, an ionic liquid tag, and others which have already been introduced into oligosaccharide synthesis. In this study, we introduced an ionic liquid tag to the building block for electrochemical glycosylation, because we presume that an ionic liquid tag works not only as a separation tag but also as an electrolyte and a reservoir of the counter anion for the reactive intermediate of glycosylation. Here we report the development of a novel ionic liquid tag and its application for electrochemical glycosylation. The developed benzyl ether-type ionic liquid tags were prepared from the corresponding precursors that can be prepared in a single step by the reaction of tertiary amines and introduced to a thioglycoside building block also in a single step with high yields. Electrochemical glycosylation of the thioglycoside equipped with the ionic liquid tag affords the corresponding disaccharides which can be purified easily by washing with water and organic solvent sequentially. In the presence of palladium carbon under the hydrogen gas atmosphere, removal of the tag and benzyl protecting groups of hydroxyl groups can be performed to obtain the fully deprotected disaccharides.

(Invited) Polymerized Ionic Liquid Block Copolymers As Solid-State Electrolytes in Alkaline Fuel Cells

Alkaline fuel cells (AFCs) that employ solid-state anion exchange membranes (AEMs) as the electrolyte separator are of great interest as they produce high power densities at low operating temperatures (< 200 °C) and enable the use of non-platinum electrodes (e.g., nickel), significantly reducing cost relative to proton exchange membrane fuel cells. Several challenges limiting the wide scale use of membrane-based AFCs is the alkaline chemical stability and ion transport of polymers used as AEMs. Recently, polymerized ionic liquid (PIL) block copolymers with a range of chemically stable heterocyclic cations have become candidates to investigate for AFCs. PIL block copolymers constitute an emerging class of polymers and a distinct set of block copolymers that synergistically combine the advantageous properties of both PILs and block copolymers and are synthetically highly versatile with numerous cation and anion chemistries available. Specifically, the unique physiochemical properties of PILs, such as high solid-state ionic conductivity, high chemical, thermal and electrochemical stability, and widely tunable physical properties (e.g., via anion exchange), are incorporated in the block copolymer architecture, which allows for self-assembly into a range of nanostructures, where morphology type and domain size are tunable. In this talk, the synthesis, alkaline chemical stability, and ion transport of numerous PIL block copolymers developed in our research group will be discussed. More specifically, both the cation and backbone chemistry have a significant effect on alkaline chemical stability and various chemistries and chain architectures have a significant impact on ion conductivity. The AFC performance of PIL block copolymers as both the electrolyte and ionomer in the catalyst layer will also be discussed.

An electrostatic mechanism for Ca(2+)-mediated regulation of gap junction channels.

Gap junction channels mediate intercellular signalling that is crucial in tissue development, homeostasis and pathologic states such as cardiac arrhythmias, cancer and trauma. To explore the mechanism by which Ca2+ blocks intercellular communication during tissue injury, we determined the X-ray crystal structures of the human Cx26 gap junction channel with and without bound Ca2+. The two structures were nearly identical, ruling out both a large-scale structural change and a local steric constriction of the pore. Ca2+ coordination sites reside at the interfaces between adjacent subunits, near the entrance to the extracellular gap, where local, side chain conformational rearrangements enable Ca2+chelation. Computational analysis revealed that Ca2+-binding generates a positive electrostatic barrier that substantially inhibits permeation of cations such as K+ into the pore. Our results provide structural evidence for a unique mechanism of channel regulation: ionic conduction block via an electrostatic barrier rather than steric occlusion of the channel pore.

Optimization of structural and dielectric properties of CdSe loaded poly(diallyl dimethyl ammonium chloride) polymer in a desired frequency and temperature window

In the present paper, investigations of CdSe loaded poly(diallyl dimethyl ammonium chloride) (PDADMAC) nanocomposites and pure PDADMAC synthesized by wet chemical technique have been carried out. Fourier transform infrared and X-ray diffraction analysis have been performed to reveal the structural details of pure polymer and polymer nanocomposite (PNC). The dielectric behavior of pure polymer and PNC has been recorded, which results in higher value of the real and imaginary part of dielectric constant for PNC, as compared with pure PDADMAC. The increase is attributed to the addition of CdSe quantum dots to the pure polymer. The contribution of ionic and electronic polarization has been observed at higher frequency. The theoretical fitting of Cole-Cole function to the experimental data of dielectric constant of PNC and pure PDADMAC results in the determination of relaxation time and conductivity of space charge carriers. The CdSe loaded polymer nanocomposite has been used as an electrolyte in the battery fabrication with configuration Al/PNC/Ag2O. The ac conductivity measurements have been carried out for both samples in a frequency window of 1 kHz–5 MHz and at different temperatures varying from 298 K to 523 K. Activation energy (Ea) has been determined for pure polymer as well as PNC and is found to be less for PNC, as compared with pure polymer. Further, impedance measurement at different temperatures results in two frequency ranges corresponding to ionic conduction and blocking electrode effect. The value of bulk resistance for pure polymer and PNC has been found to be 3660 Ω and 442 Ω, respectively, at 298 K temperature. Electric modulus has been determined and is observed to support the dielectric constant data; it further reveals the deviation from Debye behavior at a higher frequency.

Strong and tuneable wet adhesion with rationally designed layer-by-layer assembled triblock copolymer films.

In this study the wet adhesion between Layer-by-Layer (LbL) assembled films of triblock copolymer micelles was investigated. Through the LbL assembly of triblock copolymer micelles with hydrophobic, low glass transition temperature (Tg) middle blocks and ionic outer blocks, a network of energy dissipating polymer chains with electrostatic interactions serving as crosslinks can be built. Four triblock copolymers were synthesized through Atom Transfer Radical Polymerisation (ATRP). One pair had a poly(2-ethyl-hexyl methacrylate) middle block with cationic or anionic outer blocks. The other pair contained the same ionic outer blocks but poly(n-butyl methacrylate) as the middle block. The wet adhesion was evaluated with colloidal probe AFM. To our knowledge, wet adhesion of the magnitude measured in this study has not previously been measured on any polymer system with this technique. We are convinced that this type of block copolymer system grants the ability to control the geometry and adhesive strength in a number of nano- and macroscale applications.

Protein separations via thermally responsive ionic block copolymer brush layers

Thermoresponsive materials were prepared via multi-step surface-initiated ATRP. Because of the hydrophobic/hydrophilic transitions in the materials, proteins are adsorbed and eluted by simply changing the column temperature.

Anhydrous Proton Transport in Polymerized Ionic Liquid Block Copolymers: Roles of Block Length, Ionic Content, and Confinement

Anhydrous proton transport has been investigated in a series of proton conducting polystyrene-block-polymerized ionic liquid (PS-b-PIL) copolymers spanning a range of molecular weights and compositions. The PIL is a macromolecular analogue of imidazolium bis(trifluoromethane sulfonimide) (ImTFSI), a well-known proton conducting ionic liquid, and consists of imidazole linked to a polymer backbone via the 5-carbon. In contrast to prior work on nitrogen-linked imidazolium PILs, carbon-linked imidazolium has two nitrogens which can both function as proton donor/acceptors and participate in Grotthus mechanism conduction. The conductivity of the PIL block is shown to be dramatically impacted upon confinement by a PS block and can exceed the conductivity of the homopolymer in the range of 30–130 °C for PIL-rich block copolymer composition. At high temperature the conductivities track with ionic content while at room temperature the conductivities are nonmonotonic. X-ray scattering reveals a suppression of the pe...

Building Less Tortuous Ion-Conduction Pathways Using Block Copolymer Electrolytes with a Well-Defined Cubic Symmetry

We investigated the effects of morphology on the ion transport properties of polymer electrolytes. A single sulfonated block copolymer displayed a series of ordered morphologies with three-dimensional symmetry, i.e., cubic, Fddd (O70), and Fm3m (fcc) phases, upon the addition of ionic liquids. The unique phase behavior was understood on the basis of the selective swelling of the sulfonated blocks by ionic liquids and the changes in segregation strength with the modulation of the ionic interactions in the ionic phases. The type of three-dimensional lattice was revealed to play an important role in determining the ion transport properties of ionic liquid-containing sulfonated block copolymers. For example, the sample with disordered spherical lattices exhibited the highest tortuosity (∼2) for ion conduction, indicative of the considerable diffusion barriers in the conducting phases. On the contrary, the samples with well-defined orthorhombic and face-centered cubic symmetries, i.e., O70 and fcc phases, rev...

Human induced pluripotent stem cell-derived versus adult cardiomyocytes: an in silico electrophysiological study on effects of ionic current block.

Background and PurposeTwo new technologies are likely to revolutionize cardiac safety and drug development: in vitro experiments on human‐induced pluripotent stem cell‐derived cardiomyocytes (hiPSC‐CMs) and in silico human adult ventricular cardiomyocyte (hAdultV‐CM) models. Their combination was recently proposed as a potential replacement for the present hERG‐based QT study for pharmacological safety assessments. Here, we systematically compared in silico the effects of selective ionic current block on hiPSC‐CM and hAdultV‐CM action potentials (APs), to identify similarities/differences and to illustrate the potential of computational models as supportive tools for evaluating new in vitro technologies.Experimental Approach In silico AP models of ventricular‐like and atrial‐like hiPSC‐CMs and hAdultV‐CM were used to simulate the main effects of four degrees of block of the main cardiac transmembrane currents.Key ResultsQualitatively, hiPSC‐CM and hAdultV‐CM APs showed similar responses to current block, consistent with results from experiments. However, quantitatively, hiPSC‐CMs were more sensitive to block of (i) L‐type Ca2+ currents due to the overexpression of the Na+/Ca2+ exchanger (leading to shorter APs) and (ii) the inward rectifier K+ current due to reduced repolarization reserve (inducing diastolic potential depolarization and repolarization failure).Conclusions and Implications In silico hiPSC‐CMs and hAdultV‐CMs exhibit a similar response to selective current blocks. However, overall hiPSC‐CMs show greater sensitivity to block, which may facilitate in vitro identification of drug‐induced effects. Extrapolation of drug effects from hiPSC‐CM to hAdultV‐CM and pro‐arrhythmic risk assessment can be facilitated by in silico predictions using biophysically‐based computational models.

Solvent controlled ion association in structured copolymers: Molecular dynamics simulations in dilute solutions.

Tailoring the nature of individual segments within ion containing block co-polymers is one critical design tool to achieve desired properties. The local structure including the size and distribution of the ionic blocks, as well as the long range correlations, are crucial for their transport ability. Here, we present molecular dynamics simulations on the effects of varying the concentrations of the ionizable groups on the conformations of pentablock ionomer that consist of a center block of ionic sulfonated styrene tethered to polyethylene and terminated by a bulky substituted styrene in dilute solutions. Sulfonation fractions f (0 ≤ f ≤ 0.55), spanning the range from ionomer to polyelectrolytes, were studied. Results for the equilibrium conformation of the chains in water and a 1:1 mixture of cyclohexane and heptane are compared to that in implicit poor solvents with dielectric constants ε = 1.0 and 77.73. In water, the pentablock collapses with the sulfonated groups on the outer surface. As f increases, the ionic, center block increasingly segregates from the hydrophobic regions. In the 1:1 mixture of cyclohexane and heptane, the flexible blocks swell, while the center ionic block collapses for f > 0. For f = 0, all blocks swell. In both implicit poor solvents, the pentablock collapses into a nearly spherical shape for all f. The sodium counterions disperse widely throughout the simulation cell for both water and ε = 77.73, whereas for ε = 1.0 and mixture of cyclohexane and heptane, the counterions largely condense onto the collapsed pentablock.

Development and Characterization of Highly Conducting Nonfluorinated Di and Triblock Copolymers for Polymer Electrolyte Membranes

To achieve stable polymer electrolyte membranes (PEMs) with efficient ionic nano-channels, novel fully aromatic AB or ABA copolymers composed of poly(fluorenyl ether sulfone biphenyl)s (PFESBs) and poly(arylene ether sulfone)s (PAESs) were synthesized via polymerization and post-sulfonation methods, and were explored as fuel cell membranes. The structural analysis of synthesized copolymers and the corresponding membranes were ascertained by gel permeation chromatography (GPC), Fourier transform infrared (FTIR), and 1H nuclear magnetic resonance (NMR) techniques. Thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) analysis showed that the prepared membranes were thermally stable, so that elevated temperature fuel cell operation would be possible. High hydrophilic and hydrophobic nano-phase separation and obvious ionic aggregate block morphology was observed in both triblock and diblock copolymers in atomic force microscopy (AFM) phase images, which may be highly related to their proton transport ability. A sulfonated AB diblock copolymer membrane with an ion-exchange capacity (IEC) of 2.06 meq g−1 has a maximum proton conductivity of 184 mS cm−1, which is higher than that of a perfluorosulfonic acid membrane under the same measurement conditions.

Bromide and Hydroxide Conductivity–Morphology Relationships in Polymerized Ionic Liquid Block Copolymers

A polymerized ionic liquid (PIL) diblock copolymer, poly(MMA-b-MEBIm-Br), was synthesized at various compositions from an ionic liquid monomer, (1-[(2-methacryloyloxy)ethyl]-3-butylimidazolium bromide) (MEBIm-Br), and a nonionic monomer, methyl methacrylate (MMA), via the reverse addition–fragmentation chain transfer (RAFT) polymerization technique. A hydroxide-conducting PIL diblock copolymer, poly(MMA-b-MEBIm-OH), was also prepared via anion exchange metathesis of the bromide-conducting block copolymer. In a former study, the conductivity and morphology of the bromide- and hydroxide-conducting PIL diblock copolymer were examined at one fixed PIL composition: 17.3 mol %. In this study, additional PIL compositions of (6.6, 11.9, and 26.5 mol %) were explored to fully understand the previous unusual conductivity results. Both bromide and hydroxide conductivities were higher in the PIL block copolymer at PIL compositions of 11.9, 17.3, and 26.5 mol % compared to the PIL homopolymer under the same experiment...

Optimization of Block Copolymer Electrolytes for Lithium Metal Batteries

Safety is one of the most important criteria for electrochemical energy storage devices used in large scale applications such as wind or solar farms. In this context, solid polymer electrolytes based on nanostructured block copolymer electrolytes (BCEs) are promising because their properties can be finely tuned by adjusting simultaneously their block chemistries and polymer architectures. However, there is a need to rationalize the different properties of BCE that are optimal for battery applications. We produced by controlled radical polymerization a large number of BCEs based on either (1) linear poly(ethylene oxide) (PEO) or (2) comb PEO as the ionic conductor block, and polystyrene as the structural block. We varied the molecular weight of the PEO-based block, the composition, and the architecture (diblock vs triblock). We performed a systematic analysis of their thermodynamic, ionic transport, and mechanical properties. To verify the potential of BCEs as electrolytes, we evaluated their electrochemical stabilities. Laboratory scale batteries comprising the best BCEs and LiFePO4 as a positive active material were cycled at different rates and temperatures. This process allows the selection of the best architectures and compositions that had been successfully tested in battery prototypes and cycled for more than 600 cycles at high rates without any dendritic growth.

Synthesis and self-assembly of temperature and anion double responsive ionic liquid block copolymers

In this paper, double hydrophilic ionic liquid block copolymers (ILBCs), poly(N-isopropylacrylamide)-block-poly[1-methyl-3-(2-methacryloyloxy propylimidazolium bromine)] (PNIPAM-b-PMMPImB), were polymerized by two-step reversible addition-fragmentation chain transfer (RAFT) process. The composition and molecular weight distributions of ILBCs were characterized using 1HNMR and gel permeation chromatography (GPC). The self-assembly and temperature- and anion-responsive behaviors of ILBCs were investigated by UV-Vis spectroscopy, TEM and dynamic light scattering (DLS). With increasing the concentration of (CF3SO2)2N−, the micellization of self-assembling PNIPAM-b-PMMPImB was induced to form a core—shell structure containing the core with hydrophilic PMMPIm-(CF3SO2)2N− surrounded by the shell of PNIPAM via the anion-responsive properties of ILBCs. However, upon temperature increasing, PNIPAM-b-PMMPImB formed the micelles composing of PNIPAM core and PMMPImB shell. The ionic liquid segment with strong hydrophilic property enhanced the hydrogen bonding interaction which expanded the temperature range of phase transition and increased the lower critical solution temperature (LCST) of the system. These results indicate that ILBCs prepared in this paper have excellent temperature and anion double responsive properties, and may be applied as a kind of potential environmental responsive polymer nanoparticles.

Novel multi-responsive polymer materials: When ionic liquids step in

This review is focused on a novel family of multi-responsive polymer materials with the participation of ionic liquids (ILs-MRPMs). Substituting part or all the responsive elements in conventional multi-responsive polymer materials (MRPMs) with ionic liquids (ILs) by doping, grafting, and polymerization can render the polymer with significant advantages inheriting the properties of ion pairs. This approach may endow MRPMs with different responsive features, establishing a new route to building MRPMs with “ionic blocks”. Most recent studies related to the ILs-MRPMs are classified with their advantages and properties in this review. This review provides a basis to develop state-of-art MRPMs with more comprehensive and practical applications in the future.

Investigation of the colloidal Cr2O3 removal possibilities from aqueous solution using the ionic polyamino acid block copolymers

Disposal of the environmentally dangerous metal oxide suspensions from the waste water is an essential problem. The polymers adsorption can be one of the most effective and suitable methods. In the presented paper the ionic diblock copolymers impact on the Cr2O3 suspensions was investigated. The copolymer adsorption layers structure was determined on the basis of the adsorption and electrokinetic (surface charge density and zeta potential) tests. The polymers adsorption amount was measured using the static method from aqueous solutions. Additionally, the application of the turbidimetric method enabled determination of the interactions between the system constituents. Analysis of this data allows the estimation of the most probable stabilization (or destabilization) mechanism of the Cr2O3 suspensions in the presence of the studied macromolecular compounds. Hence, the Cr2O3 suspensions are unstable in the presence of the anionic copolymer at pH 3 and the cationic one in the alkaline medium.

Nanopore-Based Assay for Detection of Methylation in Double-Stranded DNA Fragments

DNA methylation is an epigenetic modification of DNA in which methyl groups are added at the 5-carbon position of cytosine. Aberrant DNA methylation, which has been associated with carcinogenesis, can be assessed in various biological fluids and potentially can be used as markers for detection of cancer. Analytically sensitive and specific assays for methylation targeting low-abundance and fragmented DNA are needed for optimal clinical diagnosis and prognosis. We present a nanopore-based direct methylation detection assay that circumvents bisulfite conversion and polymerase chain reaction amplification. Building on our prior work, we used methyl-binding proteins (MBPs), which selectively label the methylated DNA. The nanopore-based assay selectively detects methylated DNA/MBP complexes through a 19 nm nanopore with significantly deeper and prolonged nanopore ionic current blocking, while unmethylated DNA molecules were not detectable due to their smaller diameter. Discrimination of hypermethylated and unmethylated DNA on 90, 60, and 30 bp DNA fragments was demonstrated using sub-10 nm nanopores. Hypermethylated DNA fragments fully bound with MBPs are differentiated from unmethylated DNA at 2.1- to 6.5-fold current blockades and 4.5- to 23.3-fold transport durations. Furthermore, these nanopore assays can detect the CpG dyad in DNA fragments and could someday profile the position of methylated CpG sites on DNA fragments.