Molecular Displacement Research Articles

Molecular displacement approach for the electrochemical detection of protein-bound propofol

Propofol is one of the principal drugs used for the sedation of patients undergoing mechanical ventilation in intensive care units. The correct dosage of such sedative drugs is highly important, but current methods of determining infusion rates are limited and there is a lack of suitable methods for directly determining patient blood propofol concentrations. A significant challenge for the development of propofol sensors is that propofol demonstrates very high protein binding, leading to a low free fraction in blood. Here we present a method for improving the efficacy of an electrochemical propofol sensor by increasing the free fraction via a molecular displacement approach. When used in conjunction with a carbon nanotube/graphene oxide/iron oxide nanoparticle functionalised screen-printed electrode, it was found that this approach dramatically improved the sensor's sensitivity towards propofol. Ibuprofen was found to be the most effective displacement agent, with an optimal concentration of 30 mM. The resultant sensitivity was 2.82 nA/μg/ml/mm2 with a coefficient of variation of 0.07, and the limit of detection was 0.2 μg/ml. This approach demonstrates high specificity towards drugs commonly administered to intensive care patients.

Investigating zero-point vibrations of solid hydrogen via statistical moment method

Zero-point vibrations of solid hydrogen are investigated by analyzing the molecular mean-squared displacement (MSD) and mean-squared relative displacement functions within the statistical moment method approach in statistical mechanics. Numerical computations of these thermodynamic properties were conducted for solid hydrogen from 0 K to its phase transition temperature using the Wigner-Kirkwood mean-field potential derived from the Buckingham exp-6 potential. We have shown that the quantum-mechanical zero-point vibrations play an important role at low temperature. And these thermodynamic quantities increase with temperature, suggesting that both thermal and quantum effects play a significant role near the liquid-solid phase transition. The favorable consistency between our findings and the recent experimental inelastic neutron scattering measurements of MSD attests to the potential of SMM as a novel approach for determining the atomic vibrations of solid hydrogen. This approach allows us to study these effects including the anharmonicity of lattice vibrations.

High‐temperature energy storage performance of polyetherimide all‐organic composites enhanced by hindering charge hopping and molecular motion

AbstractDielectric capacitors are widely used in aerospace, power systems, and other fields. Working environments with ever‐increasing temperatures pose a new challenge to energy storage performance. Polyetherimide (PEI) has gained extensive research for its good high‐temperature properties. In order to further improve its energy storage performance at high temperatures, many researchers have worked on PEI all‐organic composites doping with molecular semiconductors. Previous studies generally only considered the effect of introduced deep traps on macroscopic properties such as electrical conductivity, electrical breakdown, and energy storage performance. It has been shown that only qualitative analyses can be performed from the perspective of charge trapping, and it is difficult to obtain quantitative results. Therefore, this work proposes to study the macroscopic properties of polymer dielectrics by combining charge trapping with molecular displacement. A comprehensive conduction‐breakdown‐energy storage model was established to explain the influence mechanism of molecular semiconductors on the improved energy storage performance of PEI composites at high temperatures. The molecular semiconductor fillers increase the coefficient of friction between molecular chains, which restricts the movement of molecular chains and also limits charge hopping. Therefore, the dielectrics have higher breakdown strengths and smaller conduction losses, which synergistically enhance the energy storage performance.

Improved high temperature energy storage density and efficiency of polyimide nanocomposites via hindering charge and molecular motions

Electric vehicles and renewable energy consumption have huge demands for high-performance polymer dielectric capacitors. However, the resistivity and breakdown strength of existing polymer dielectrics deteriorate significantly at high temperatures, reducing the energy storage density and charge-discharge efficiency of capacitors below service requirements. The charge transport and molecular chain motion characteristics in linear polymers determine their conductivity, breakdown, and energy storage properties, but the quantitative relationship between them is not clear. An in-situ polymerization method was used to prepare polyimide/Al2O3 nanocomposites (PI/Al2O3 PNCs). Experimental results show that the resistivity, breakdown strength, energy storage density, and charge-discharge efficiency of PNCs increase initially and then decrease with increasing doping content, peaking at 3 wt%. The discharged energy density of PI/Al2O3-3 wt% PNCs at 180°C is 207.52 % higher than pure PI. A conductance-breakdown-energy storage co-simulation model based on charge transport and molecular chain displacement was used to simulate the voltage-current, breakdown, and energy storage characteristics of PNCs. The simulation results are consistent with the experiments. Comparative studies between simulation and experiments show that the independent interface zone between nanofillers and PI hinders charge transport and molecular chain movement, reducing electric field distortion and molecular chain spacing, thereby improving high-temperature breakdown and energy storage performance of PNCs.

Ceanothanes Derivatives as Peripheric Anionic Site and Catalytic Active Site Inhibitors of Acetylcholinesterase: Insights for Future Drug Design.

Alzheimer's disease (AD) is a multifactorial and fatal neurodegenerative disorder. Acetylcholinesterase (AChE) plays a key role in the regulation of the cholinergic system and particularly in the formation of amyloid plaques; therefore, the inhibition of AChE has become one of the most promising strategies for the treatment of AD, particularly concerning AChE inhibitors that interact with the peripheral anionic site (PAS). Ceanothic acid isolated from the Chilean Rhamnaceae plants is an inhibitor of AChE through its interaction with PAS. In this study, six ceanothic acid derivatives were prepared, and all showed inhibitory activity against AChE. The structural modifications were performed starting from ceanothic acid by application of simple synthetic routes: esterification, reduction, and oxidation. AChE activity was determined by the Ellmann method for all compounds. Kinetic studies indicated that its inhibition was competitive and reversible. According to the molecular coupling and displacement studies of the propidium iodide test, the inhibitory effect of compounds would be produced by interaction with the PAS of AChE. In silico predictions of physicochemical properties, pharmacokinetics, drug-likeness, and medicinal chemistry friendliness of the ceanothane derivatives were performed using the Swiss ADME tool.

Evaluating the biomolecular interaction between delamanid/formulations and human serum albumin by fluorescence, CD spectroscopy and SPR: Effects on protein conformation, kinetic and thermodynamic parameters

Delamanid is an anti-tuberculosis drug used for the treatment of drug-resistant tuberculosis. Since delamanid has a high protein bound potential, even patients with low albumin levels should experience high and rapid delamanid clearance. However, the interaction between delamanid and albumin should be better controlled to optimize drug efficacy. This study was designed to evaluate the binding characteristics of delamanid to human serum albumin (HSA) using various methods: fluorescence spectroscopy, circular dichroism (CD), surface plasmon resonance (SPR), and molecular docking simulation. The fluorescence emission band without any shift indicated the interaction was not affected by the polarity of the fluorophore microenvironment. The reduction of fluorescence intensity at 344 nm was proportional to the increment of delamanid concentration as a fluorescence quencher. UV-absorbance measurement at the maximum wavelength (λmax, 280 nm) was evaluated using inner filter effect correction. The HSA conformation change was explained by the intermolecular energy transfer between delamanid and HSA during complex formation. The study, which was conducted at temperatures of 298 K, 303 K, and 310 K, revealed a static quenching mechanism that correlated with a decreased of bimolecular quenching rate constant (kq) and binding constant (Ka) at increased temperatures. The Ka was 1.75–3.16 × 104 M−1 with a specific binding site with stoichiometry 1:1. The negative enthalpy change, negative entropy change, and negative Gibbs free energy change demonstrated an exothermic-spontaneous reaction while van der Waals forces and hydrogen bonds played a vital role in the binding. The molecular displacement approach and molecular docking confirmed that the binding occurred mainly in subdomain IIA, which is a hydrophobic pocket of HSA, with a theoretical binding free energy of −9.33 kcal/mol. SPR exhibited a real time negative sensorgram that resulted from deviation of the reflex angle due to ligand delamanid-HSA complex forming. The binding occurred spontaneously after delamanid was presented to the HSA surface. The SPR mathematical fitting model revealed that the association rate constant (kon) was 2.62 × 108 s−1M−1 and the dissociation rate constant (koff) was 5.65 × 10−3 s−1. The complexes were performed with an association constant (KA) of 4.64 × 1010 M−1 and the dissociation constant (KD) of 2.15 × 10−11 M. The binding constant indicated high binding affinity and high stability of the complex in an equilibrium. Modified CD spectra revealed that conformation of the HSA structure was altered by the presence of delamanid during preparation of the proliposomes that led to the reduction of secondary structure stabilization. This was indicated by the percentage decrease of α-helix. These findings are beneficial to understanding delamanid-HSA binding characteristics as well as the drug administration regimen.

High temperature electrical breakdown and energy storage performance improved by hindering molecular motion in polyetherimide nanocomposites

Polyetherimide (PEI) is widely used as a material for high temperature and high power energy storage capacitors in new energy vehicles and other fields. However, as the temperature increases, the electrical conductivity increases and the breakdown strength decreases, which greatly reduces the energy storage density of the capacitor and limits the application range. In order to clarify the influence mechanism of high temperature on the breakdown and energy storage performance of dielectrics, this paper established a charge capture and molecular displacement (CTMD) breakdown model based on the expansion motion of molecular segments to study the charge transport and molecular chain motion process of PEI nanocomposites (PNCs) at high temperature. The results show that at 100 °C, compared with pure PEI, the internal maximum molecular displacement of PEI PNCs with appropriate doping content (3 wt%) is reduced by 28.79 %, and the breakdown strength is increased by 11.20 %. Appropriate nano-doping can effectively increase the movement difficulty of molecular chains and reduce the activation volume that provides energy for charge transport. Thus, charge transport is inhibited, current density is reduced, and Joule heat accumulation is avoided. Finally, the high temperature breakdown and energy storage performance are improved.

Exploring the molecular basis of tucatinib interaction with human serum albumin: A spectroscopic and computational analysis

This study delves into the kinetics of interaction among anticancer drug tucatinib (TCT) and human serum albumin (HSA), a pivotal protein that transports substances in the bloodstream of humans. Employing biophysical techniques alongside in-silico approaches, the TCT-HSA complex formation is substantiated. This binding interaction is unequivocally confirmed by the inverse relationship between temperature and Stern-Volmer constant (KSV) and the hyperchromicity in UV–visible spectra. The binding constant (Kb) value (5.34 x 104 M−1) indicates a moderate affinity between TCT and HSA, with thermodynamic analysis pointing towards stabilization through hydrogen bonds and hydrophobic and van der Waals interactions. Moreover, despite causing alterations in the vicinity of Tyr and Trp amino acids, the introduction of TCT to HSA confers a substantial protective effect against the thermal denaturation of the protein. Circular dichroism unveils a decrease in the content of alpha helices upon TCT binding. At the same time, CD thermal analysis hints at a marginal increase in the melting temperature of HSA, indicating heightened stability at elevated temperatures. Molecular docking and competitive displacement assays confirm that the preferred binding site for TCT is subdomain IIA (Sudlow's site I) of HSA. Molecular dynamics simulations emphasize the stability of the TCT-HSA complex. This work sheds light on a detailed characterization of the HSA-TCT interaction, elucidating binding mechanisms and their consequential impact on HSA structure and stability.

Deciphering the binding mechanism of gingerol molecules with plasma proteins: implications for drug delivery and therapeutic potential

Ginger is a highly valued herb, renowned globally for its rich content of phenolic compounds. It has been traditionally used to treat various health conditions such as cardiovascular diseases, digestive issues, migraines, Alzheimer’s disease, tumor reduction and chronic inflammation. Despite its potential medicinal applications, the therapeutic effectiveness of ginger is hindered by its limited availability and low plasma concentration levels. In this study, we explored the interaction of ginger’s primary phenolic compounds, specifically 6-gingerol (6 G), 8-gingerol (8 G) and 10-gingerol (10 G), with plasma proteins which are human serum albumin (HSA) and α-1-acid glycoprotein (AGP). These two plasma proteins significantly influence drug distribution and disposition as they are key binding sites for most drugs. Fluorescence emission spectra indicated strong binding of 6, 8 and 10 G with HSA, with binding constants of 2.03 ± 0.01 × 104 M−1, 4.20 ± 0.01 × 104 M−1 and 6.03 ± 0.01 × 106 M−1, respectively. However, the binding of gingerols with AGP was found to be negligible. Molecular displacement by site-specific probes and molecular docking analyses revealed that gingerols bind at the IIA domain, with stability provided by hydrogen bonds, van der Waals forces, conventional hydrogen bonds, carbon-hydrogen bonds, alkyl and Pi–alkyl interactions. Further, the partial unfolding of the protein was observed upon binding the gingerol compound with HSA. In addition, molecular dynamic simulations demonstrated that gingerols remained stable in the subdomain IIA over 100 ns. This stability, coupled with Molecular Mechanics Generalized Born Surface Area indicating free energies of −43.765, −57.504 and −66.69 kcal/mol for 6, 8 and 10 G, respectively, reinforces the robust binding potential of these compounds. Circular dichroism studies suggested that the interaction of gingerols leads to the minimal transformation of HSA secondary structure, with the pattern being 10 G > 8 G > 6 G, a finding further substantiated by root mean square deviation and root mean square fluctuation fluctuations. These results propose that HSA has a stronger affinity to gingerols than AGP, which could have significant implications on the therapeutic circulating levels of gingerols. Communicated by Ramaswamy H. Sarma

A fluorescent "Turn-ON" probe with rapid and differential response to HSA and BSA: quantitative detection of HSA in urine.

The present study provides insight into the differential response of a benzimidazole-malononitrile fluorescent "Turn-ON" probe on interaction with two structurally similar proteins, BSA and HSA. Compound 6 shows more sensitivity towards the two SAs, which is completely lost in the case of compound 7, synthesized by substitution on 6. The aggregates of compound 6 show absorption maxima at 385 nm and weak emission maxima at 565 nm. Compound 6 forms a new emission band at 475 nm on gradual addition of BSA (200 μM) along with a slight increase in the emission band at 565 nm. However, on addition of HSA (50 μM), a new band at 475 nm is formed. In contrast to BSA, in the case of HSA, 50% quenching is observed in the emission band of compound 6 at 565 nm. The new band formed on the interaction of 6 with BSA shows four-fold more enhancement compared to HSA. Furthermore, the mechanism of interaction of 6 with serum albumin has been investigated through lifetime-fluorescence analysis, site-selective drug experiments, dynamic light scattering, FE-SEM, FT-IR, etc. Molecular docking studies and site marker drug displacement experiments reveal differential interactions of 6 towards the two structurally similar proteins. Aggregates of 6 with an average hydrodynamic size of 100-190 nm are disassembled on adding BSA and HSA, and the size of the serum albumin and 6 complex decreases to 10-20 nm, revealing the ligand's encapsulation in the serum albumin cavity. Practical applicability for the quantitative detection of HSA in human urine samples is also demonstrated. The high binding affinity, sensitivity, selectivity and differential response of probe 6 towards two serum albumins (HSA and BSA) and significant quantification of HSA in urine samples shows the potential ability of this probe in medical applications.

Shape memory and self-healing in a molecular crystal with inverse temperature symmetry breaking.

Mechanically responsive molecular crystals have attracted increasing attention for their potential as actuators, sensors, and switches. However, their inherent structural rigidity usually makes them vulnerable to external stimuli, limiting their usage in many applications. Here, we present the mechanically compliant single crystals of penciclovir, a first-line antiviral drug, achieved through an unconventional ferroelastic transformation with inverse temperature symmetry breaking. These crystals display a diverse set of self-restorative behaviors well above room temperature (385 K), including ferroelasticity, superelasticity, and shape memory effects, suggesting their promising applications in high-temperature settings. Crystallographic analysis reveals that cooperative molecular displacement within the layered crystal structure is responsible for these unique properties. Most importantly, these ferroelastic crystals manifest a polymer-like self-healing behavior even after severe cracking induced by thermal or mechanical stresses. These findings suggest the potential for similar memory and restorative effects in other molecular crystals featuring layered structures and provide valuable insights for leveraging organic molecules in the development of high-performance, ultra-flexible molecular crystalline materials with promising applications.

Distribution of CO2-CH4 in a nanoslit medium and the efficiency of displacement of CH4 by CO2

The replacement of CH4 with CO2 in reservoirs is crucial for natural gas exploitation and sequestration of CO2. Therefore, the states and distribution patterns of coexisting CO2 and CH4 and the dynamic patterns of CH4 displacement by CO2 in mineral slits must be understood. Here, we simulate the molecular dynamics and displacement efficiency of CH4 in gypsum, quartz, and illite mineral slit models. The results demonstrate that gas density is not uniform throughout the slits and prove that gypsum and quartz have a greater adsorption capacity for CO2 than for CH4 and illite has a greater adsorption capacity for CH4. We find that (1) the application of the same force to different mineral slits leads to dissimilar CH4 displacement efficiencies, whereas an increase in the applied force in the same mineral slit is positively correlated with the CH4 displacement efficiency; (2) the main factor affecting CH4 displacement efficiency is CO2 adsorption; (3) the greater the adsorption capacity of mineral slits for CO2 (such as for gypsum), the more difficult it is to displace the CH4 in the slit despite large applied force; and (4) CH4 displacement efficiencies of illite, quartz, and gypsum decrease under the same conditions. These results provide a reference for theoretical research and industrial applications related to geologic carbon sequestration.

Study on space charge accumulation characteristics of 320 kV cross-linked polyethylene cable joints

High-Voltage Direct Current (HVDC) cable accessories are the key equipment to connect HVDC cables, and also the weak link in the cable system. In order to investigate the transport characteristics of space charge in cable joints, a two-dimensional axisymmetric cable joint model was established using the bipolar charge transport model, and its space charge and electric field distribution were analyzed through numerical simulation. Furthermore, the effects of the trap depth based on molecular chain displacement and temperature field on interface charge distribution of cable joint were compared with the basic model, respectively. The results show that the stress cone root and the top of the high-voltage shield are easy to accumulate space charges, which will lead to electric field distortion. The trap depth based on molecular chain displacement is larger than that of basic model at the insulation interface, which hinders the charge transport. The model without considering the effect of temperature field accumulates less charge, and the electric field and space charge at the stress cone root and the top of the high-voltage shield change gently with time. The above research results can provide a reference for the design and optimization of cable joints.

Orthogonal activation of a DNA molecular reaction network for proteinase-free and highly specific mRNA imaging in live cells

Construction of artificial DNA molecular reaction networks (DMRNs) represents an effective approach in biosensing. Here we developed a reaction network consisting of a dual catalytic hairpin assembly-mediated tandem molecular circuit combined with strand displacement reaction (DCHA-SDR) for proteinase-free and highly specific mRNA imaging in living cells. The strand displacement reaction (SDR) was designed to be orthogonally activated in exact order by two fuel strands that separately split into inactive species and grafted into the dual catalytic hairpin assembly-mediated molecular tandem circuit (DCHA). The fuel strands can be activated only when the specific mRNA is introduced, and DCHA is initiated by using two different pieces of mRNA sequences as target. In this way, the target mRNA can be automatically matched twice to obtain an accurate and amplified recognition. Comparative analysis indicates that this orthogonal strategy for target identification is superior to the strategy consisting of single CHA-mediated molecular circuit and strand displacement reaction (SCHA-SDR). Moreover, we demonstrate that the DCHA-SDR system comes with the benefit of proteinase-free progress, which makes the approach suitable for operation in living cells. Final application in various cancer cells and normal cells reveals its enormous potential for highly specific mRNA imaging in biological systems.

Selective Molecular Recognition and Indicator Displacement Sensing of Neurotransmitters in Cellular Environments.

Flexible, water-soluble hosts are capable of selective molecular recognition in cellular environments and can detect neurotransmitters such as choline in cells. Both cationic and anionic water-soluble self-folded deep cavitands can recognize suitable styrylpyridinium dyes in cellular interiors. The dyes selectively accumulate in nucleotide-rich regions of the cell nucleus and cytoplasm. The hosts bind the dyes and promote their relocation to the outer cell membrane: the lipophilic cavitands predominantly reside in membrane environments but are still capable of binding suitable targets in other cellular organelles. Incubating the cells with structurally similar biomarkers such as choline, cholamine, betaine, or butyrylcholine illustrates the selective recognition. Choline and butyrylcholine can be bound by the hosts, but minimal binding is seen with betaine or cholamine. Varying the dye allows control of the optical detection method, and both "turn-on" sensing and "turn-off" sensing are possible.

Multiscale Acoustic Properties of Nanoporous Materials: From Microscopic Dynamics to Mechanics and Wave Propagation

Despite significant progress in deciphering the mechanical properties of nanoporous materials, the intimately related phenomenon of acoustic wave propagation in such solids remains largely unexplored at this vanishing length scale (i.e., the molecular scale). Here, we report a multiscale approach to estimate the acoustic properties of zeolites─a prototypical class of nanoporous materials─by combining molecular dynamics simulations and a rigorous upscaling approach using continuum mechanics. Two different zeolites are considered, i.e., RHO and JST zeolites; while they share a simple yet different crystallographic structure, the latter shows auxeticity. First, microscopic simulations are used to calculate the speed of sound from the phonon spectrum as obtained using molecular displacement and velocity data. As an alternate route, macroscopic mechanical constants of the materials are also determined to confirm the inferred acoustic velocities by solving the Kelvin–Christoffel equation. These mechanical constants are obtained either using the strain fluctuations in a simulation performed at equilibrium or from the slope of the stress–strain curve assessed using simple mechanical tests. Second, we propose a nano-to-macro modeling strategy in which the inputs for the continuum-level upscaled model are the specific outcomes from the molecular calculations (e.g., speeds of sound, mechanical parameters). This strategy allows determining the acoustic properties of an empty double porosity material formed by adding an extra scale of porosity to a nanoporous skeleton. Such an extra scale of porosity can represent larger pores, voids in between consolidated nanoporous grains, and/or possible large defects or microfractures in the nanoporous skeleton whose effects can be probed by acoustic waves. This work paves the way for further studies in the field of nanoscale acoustics─especially in the context of applications involving nanoporous materials.

Elucidation of binding mechanism of rhodanine derivative P4OC on bovine serum albumin

Rhodanine is an important scaffold in medicinal chemistry and it act as potent anticancer agent and other pharmacological effects. In pharmacokinetics and pharmacodynamics studies of the drug, the drug binding properties on serum protein is crucial for producing better drug. This study was designed to explore the binding interactions between the Rhodanine derivative (P4OC) on Bovine Serum Albumin (BSA). The interactions between P4OC and BSA were investigated using biophysical approach and molecular docking. The quenching mechanism and binding constants of P4OC on BSA were determined by biophysical approach through fluorescence spectroscopic experiments. Circular dichroism (CD) spectroscopy was used to study the secondary structural changes of BSA upon P4OC binding. The fluorescence experiments of P4OC binding on BSA show good drug binding with static quenching constants using stern Volmer plot and found the quenching constant value K P4OC = 1.12762 × 1013 M−1 with corresponding binding free energy (ΔG) −2.303 kcal/mol. The molecular displacement fluorescence emission on BSA–P4OC complex by site specific markers shows that P4OC binds at I A sub-domain of BSA further confirmed peak shift by synchronous fluorescence of P4OC on BSA with tyrosine, tryptophan and phenylalanine amino acids. Increasing concentration of P4OC on BSA found secondary structural changes, the percentage of α-helix was decreased as well increase percentage of β-sheet and random coil. The binding of P4OC to BSA was computationally studied by molecular docking methods. Thus, results obtained are in excellent agreement with experimental and theoretical results with respect to the binding mechanism and binding constant of P4OC on BSA. We concluded that, the rhodanine derivative P4OC possesses good drug binding properties on BSA. Further P4OC may be evaluated its potential pharmacological activities on clinical trial. Communicated by Ramaswamy H. Sarma

Zero-point motion of liquid and solid hydrogen

We present an inelastic neutron scattering study of liquid and solid hydrogen carried out using the wide Angular Range Chopper Spectrometer at Oak Ridge National Laboratory. From the observed dynamic structure factor, we obtained empirical estimates of the molecular mean-squared displacement and average translational kinetic energy. We find that the former quantity increases with temperature, indicating that a combination of thermal and quantum effects is important near the liquid-solid phase transition, contrary to previous measurements. We also find that the kinetic energy drops dramatically on melting of the crystals, a consequence of the large increase in molar volume together with the Heisenberg indeterminacy principle. Our results are compared with quantum Monte Carlo simulations based on different model potentials. In general, there is good agreement between our findings and theoretical predictions based on the Silvera-Goldman and Buck potentials.

Dynamic molecular ordering in multiphasic nanoconfined ionic liquids detected with time-resolved diffusion NMR

Molecular motion in nanosized channels can be highly complicated. For example, water molecules in ultranarrow hydrophobic nanopores move rapidly and coherently in a single file, whereas by increasing the pore size they organize into coaxial tubes, displaying stratified diffusion. Interestingly, an analogous complex motion is predicted in viscous charged fluids, such as room temperature ionic liquids (RTILs) confined in nanoporous carbon or silica; however, experimental evidence is still pending. Here, by combining 1H NMR diffusion experiments in different relaxation windows with molecular dynamics simulations, we show that the imidazolium-based RTIL [BMIM]+[TCM]−, entrapped in the MCM-41 silica nanopores, exhibits an intricate dynamic molecular ordering; adsorbed RTIL molecules form a fluctuating charged layer near the pore walls, while in the bulk pore space they diffuse discretely in coaxial tubular shells, with molecular mean square displacement following a nearly ∼τ0.5 time dependence, characteristic of single file diffusion.

Ultrasensitive electrochemical platform for the p53 gene via molecular beacon-mediated circular strand displacement and terminal deoxynucleotidyl transferase-mediated signal amplification strategy.

As an important tumor suppressor gene, the p53 gene is considered to be a typical biomarker for the early diagnosis and prognosis evaluation of severe cancer. Herein, an electrochemical biosensor was proposed for the ultrasensitive detection of the p53 gene based on molecular beacon-mediated circular strand displacement polymerization combined with terminal deoxynucleotide transferase-mediated template-free DNA extension. Firstly, the p53 gene opened the hairpin structure of the molecular beacon, thereby exposing the binding sequence region of the primer DNA. The circular strand displacement polymerization occurred in the presence of the primer DNA and phi29 DNA polymerase, subsequently resulting in the circulation of the p53 gene. With the catalysis of the terminal deoxynucleotide transferase, the 3'-OH terminal sequence of the molecular beacon elongated to produce long single-stranded DNA under the template-free DNA extension. Methylene blue bound with such DNA strands generated a strong differential pulse voltammetry (DPV) signal with a peak potential of -0.28 V. Under the optimal detection conditions, the DPV signal of methylene blue showed good linear relationships with the logarithm value of the p53 gene in two concentration ranges of 0.05 fM to 3 pM and 5 fM to 100 fM, and the detection limit of the p53 gene was as low as 0.018 fM. This electrochemical biosensor possessed high recognition ability for the p53 gene in its analogues and was successfully applied for p53 gene analysis in human serum samples.