Guest Molecules Research Articles

Novel Electrochemical Sensor Based on One-Step Encapsulation of Metal-Organic Framework (MOF) for Simultaneous Detection of SARS-CoV and SARS-CoV-2.

This study investigates three metal-organic frameworks (MOFs) with distinct Brunauer-Emmett-Teller (BET) surface areas and pore sizes: MOFZr (1274 m2/g, <0.7 nm), MOFAl (371 m2/g, 1.5 nm), and MOFCr (1917 m2/g, 2 nm). Methylene blue (MB, 1.4 × 0.7 × 0.2 nm3) and triferrocene (tri-FC, 1.2 × 0.9 × 0.3 nm3) were adsorbed onto these MOFs. Specific DNA segments targeting SARS-CoV-2 (PR and PO) were employed to block the pores of the MOFs, leading to the formation of DNA-gated MOFs: MOFX/MB/PR and MOFX/tri-FC/PO. These constructs were subsequently integrated with four-arm poly(ethylene glycol) amine (4-arm-PEG-NH2)-modified gold electrodes to create the corresponding sensors (MOFX/MB/PR+MOFX/tri-FC/PO@4-arm-PEG-NH2@Au NPs@GCE). The DNA-gated MOFAl system exhibited the highest loading capacity and a 3-fold increase in sensing efficiency following the introduction of SARS-CoV-2 target DNA, surpassing the performance of the other systems. This study highlights the enhancement of the DNA-gated MOFs when the three-dimensional structures of the guest molecules closely align with the pore sizes of the MOFs. It emphasizes a critical aspect of the traditional design approach for electrochemical sensors based on MOF encapsulation, which often prioritizes BET surface areas while neglecting the compatibility between the sizes of guest molecules and MOF pore diameters. Moreover, the sensor effectively discriminated between SARS-CoV-2 and SARS-CoV by precisely aligning the SARS-CoV-2 target DNA with PR and PO. In contrast, the specific genetic targets (SR) from SARS-CoV showed complete mismatches with PO and a three-base deviation with PR. This differentiation was achieved in a simple one-step assay, even in 5% serum, across a linear concentration range of 10-9 to 10-14 M. This range signifies an expansion of 2 to 3 orders of magnitude compared to sensors that inaccurately selected MOFs.

Dynamic Two-Dimensional Covalent Organic Frameworks with Large Solvent-Induced Lattice Expansion.

Dynamic covalent organic frameworks (COFs) can switch reversibly between crystalline phases with different unit cell parameters and porosities upon physisorption of guest molecules. While impressive changes in unit cell volumes have been realized for three-dimensional frameworks, the solvent-induced volume changes of two-dimensional (2D) COFs have remained comparably small. We have now developed a series of 2D COFs where we systematically varied the length of the interconnecting bridge units. The optimized materials achieve solvent-induced expansions of up to 85% relative to the volume of the solvent-free contracted COFs. These structural changes are fully reversible and the frameworks fully retain their high degree of crystalline order. This study introduces a versatile design strategy for dynamic 2D COFs, which could enable future applications of these materials in gas separation and sensing.

Mechanically Interlocked Macrocycles on Covalent Networks for Energy and Environmental Applications.

Macrocycles' unique properties of interacting with guest molecules have been an intriguing scientific endeavor for many decades. They are potentially practically useful for engineering applications, especially in energy and environmental applications. These applications are usually demanding, involving a high temperature, pH, voltage, etc., thus, finding suitable substrates that can endure working environments and sustain macrocycles' properties is highly desirable. In that sense, covalent networks are ideal as they are chemically/electrochemically/thermally stable and can be porous by design. Emerging porous materials, especially covalent organic frameworks (COFs), could be suitable as their porous spaces allow macrocycles to interact with guest species. In the past seven years, we have seen the rise of mechanically interlocked macrocycles on covalent networks (MIMc-CNs) that translate macrocycles' properties into macroscale materials. In this conceptual review, we first describe the idea of integrating MIMcs into COFs or conventional amorphous polymers. Next, we review the reported representative MIMc-CNs used in energy and environmental applications. We also provide a brief outlook for the future directions for the MIMc-CNs research.

Low-field MRI study of the 1H distribution and migration in porous sediments during natural gas conversion from methane hydrate

Gas hydrates, crystalline compounds formed from water and guest molecules like methane, are gaining attention as a promising clean energy source. While research has extensively focused on the extraction and transport of natural gas hydrates from offshore marine sediments, the dynamic processes in the porous sediments remain under explored. This study employs low-field Magnetic Resonance Imaging (MRI) to investigate the in-situ formation and dissociation of methane hydrate within a partially saturated stack of glass beads. By integrating advanced MRI techniques, including 1D dhk SPRITE, bulk T1 distribution, and 2D spatial T2 imaging, this research provides a comprehensive analysis of fluid distribution and migration during phase transitions in the porous sediments. Three key findings emerged from the study. First, SE-SPI measurements successfully quantified hydrate and residual water saturation, aligning with previous X-ray CT and high-field MRI studies and validating low-field MRI for hydrate research. Secondly, this study introduced a volumetric approach to T1 and T2 measurements, distinguishing between free and bound water, with characteristic relaxation times for each, confirming the technique's capability to differentiate types of residual water. Finally, spatially resolved T2 relaxation time distributions revealed vertical fluid migration within the pore spaces, identifying an equilibrium zone where inflow and outflow rates were balanced. Overall, this study underscores the effectiveness of low-field MRI as a noninvasive tool for analyzing hydrate-bearing sediments. The findings lay the groundwork for further exploration of hydrate in porous sediments, enhancing our understanding of gas production dynamics in hydrate-rich environments.

Organic doped red room-temperature afterglow materials based on 2,3,5-triarylfuro[3,2-b]pyridines through Förster-resonance energy transfer

A series of novel 2,3,5-triarylfuro[3,2-b]pyridines are designed and acquired to be used as the guest molecules in organic doped room-temperature phosphorescence (RTP) system. Phenyl(pyridin-2-yl)methanone which can provide the rigid and tight microenvironment is chosen as the host molecule, which enables the two-component doped materials to emit RTP emissions of 0.5–8 s with 41–565 ms phosphorescence lifetimes and 2.9–19.4 % phosphorescence quantum efficiencies through constricting the non-radiative decay of triplet excitons. Furthermore, using commercial dyes Erythrosin B sodium salt and Eosin Y sodium salt as the third component and energy acceptor, the three-component materials emit bright red afterglows of 2 s with delayed lifetimes of 252–286 ms and emission quantum yields of 5.1–5.6 %, which are demonstrated to come from the triplet-to-singlet Förster-resonance energy transfer (FRET) from phosphorescence emission of 2,3,5-triarylfuro[3,2-b]pyridine derivative to fluorescence emission of commercial dye. This work not only provides valuable reference for the development of furo[3,2-b]pyridine-based afterglow materials, but also proves that the strategy of the FRET process provides new possibilities for molecules that can only emit fluorescence to participate in constructing afterglow materials.

Stretch-Induced Ordering of Prochiral Dimethyl Sulfoxide in Anisotropic Hydrogels Analysed by 1H and 2H Nuclear Magnetic Resonance.

Nuclear spins in small molecules dissolved in stretched hydrogels typically have population-averaged residual interactions. The nuclear magnetic resonance (NMR) spectra of these systems often show additional peaks and splittings compared with free solutions. Residual dipolar couplings (RDCs) and quadrupolar couplings (RQCs) are observed for guest1H or2H nuclear spins, respectively. Dimethyl sulfoxide (DMSO) is an exquisitely sensitive probe of such biologically relevant environments since it is prochiral and becomes effectively chiral when embedded in anisotropic gelatin-based hydrogels. Measured1H RDCs and2H RQCs were used to estimate bond order parametersover a wide range of stretching extents.At the largest extent of stretching, the2H splittings were-73.0 and-9.4 Hz, similar to those found for guest molecules in liquid crystals. Inhomogeneous line broadening of the2H resonances was related to the size of the RQC due to a spatial distribution of RQCs, which was revealed using a one-dimensional slice selective imaging experiment along the stretching direction.1H NMR spectra exhibited homogeneous line broadening, with resonance integrals that indicated concealed multiplet structure. Understanding molecular bond ordering in mechanically oriented environments provides a conceptual framework for investigating more complex systems including zeolites and those foundin vivo.

Stimulating Chiral Selective Expression of Room Temperature Phosphorescence for Chirality Recognition.

Chiral recognition is crucial for applications in chiral purity assessment and biomedical fields. However, achieving chiral recognition through visible roomtemperature phosphorescence remains challenging. Here, two chiral molecules, designated as host and guest are synthesized, which possess similar structural configurations. A viable strategy involving a chiral configuration-dependent energy transfer process to enable selective phosphorescence expression is proposed, thereby enabling chiral recognition in a host-guest doping system. The chiral and structural similarity between host and guest facilitates efficient Dexter energy transfer due to the reduced spatial distance between the molecules. This mechanism significantly enhances the intensity of red phosphorescence from the guest molecule, characterized by an emission peak at 612nm and a prolonged lifetime of 32.7ms. This work elucidates the mechanism of chiral-dependent energy transfer, demonstrating its potential for selectively expressing phosphorescence in chiral recognition.

Hofmann Clathrates: A "Blue Box" Approach to Modulate Spin-Crossover Properties.

Hofmann coordination polymers (CPs) with cationic ligands provide an innovative strategy for recognizing π-electron-rich aromatic molecules - similar to the "little blue box". In this study, we demonstrate that hydroquinone molecules can be incorporated into these coordination polymers when redox-active bipyridinium derivatives are used as axial ligands. The insertion leads to a significant structural modification, resulting in a shift of the spin transition by 150 K and an approximate 23 % increase in volume, caused by the strong donor-acceptor π-π stacking interaction formed between the ligands and the guest molecule. These findings have been confirmed through temperature-dependent single crystal X-ray diffraction, magnetic measurements and optical reflectivity measurements.

Hofmann Clathrates: A “Blue Box” Approach to Modulate Spin‐Crossover Properties

AbstractHofmann coordination polymers (CPs) with cationic ligands provide an innovative strategy for recognizing π‐electron‐rich aromatic molecules – similar to the “little blue box”. In this study, we demonstrate that hydroquinone molecules can be incorporated into these coordination polymers when redox‐active bipyridinium derivatives are used as axial ligands. The insertion leads to a significant structural modification, resulting in a shift of the spin transition by 150 K and an approximate 23 % increase in volume, caused by the strong donor‐acceptor π‐π stacking interaction formed between the ligands and the guest molecule. These findings have been confirmed through temperature‐dependent single crystal X‐ray diffraction, magnetic measurements and optical reflectivity measurements.

Visible Light-Responsive Crystalline B←N Host Adducts with Solvent-Induced Allosteric Effect for Guest Release.

Photo-responsive organic crystals, capable of converting light energy into chemical energy to initiate conformational transitions, present an emerging strategy for developing lightweight and versatile smart materials. However, visible light-triggered tailored guests capture and release behaviors in all-organic solids are rarely reported. Here, we introduce a photoreactive crystalline boron-nitrogen (B←N) host adduct with the ability to undergo [2+2] photocycloaddition upon 447 nm light exposure. This process facilitates single-crystal-to-single-crystal (SCSC) photodimerization in the mother liquor, maintaining the original B←N host structure. Weakened intermolecular interactions within the photodimer host contribute to fast guest release in air under irradiation. Furthermore, the dynamic B←N bonds enable reversible transformations between organic host adducts and adduct cocrystals under the solvent-induced allosteric effect. As a result, four B←N host adduct crystals containing individual alkane guest are easily obtained and exhibited the ability of photo-controlled alkane release. Therefore, the integration of photo reactivity and structural transformation within B←N host adduct enables customized capture and release of guest molecules.

RP-HPLC Study of the Complexation of Acetamiprid, Imidacloprid and Carboxin Guest Molecules With Thiophosphorylated Calix [6] Arene in Dimethylformamide-Acetonitrile-Water Mobile Phase.

Reversed-phase high-performance liquid chromatography was used to study the host-guest complexation of thiophosphacalixarenes (TPC 1-3) with acetamiprid, imidacloprid and carboxin as guests. The Onyx Monolithic C 18 column (150 × 0.1mm) and Phenomenex® were used with UV detection at 254nm. The mobile phase consisted of dimethylformamide-acetonitrile-water. The association constant of the 1:1 guest-host complexes was determined from the relationship between the retention factor of the guest and concentration of the thiophosphacalix [6] arene host in the mobile phase. The stability constants are influenced by size, nature, position and quantity of substituents in the benzene ring of the calixarene skeleton. The detection limits for TPC 1, TPC 2 and TPC 3 are 0.95, 1.20 and 1.40μg/mL, while the quantification limits are 2.85, 3.60 and 4.20μg/mL for TPC 1, TPC 2 and TPC 3, respectively.

Visible Light‐Responsive Crystalline B←N Host Adducts with Solvent‐Induced Allosteric Effect for Guest Release

AbstractPhoto‐responsive organic crystals, capable of converting light energy into chemical energy to initiate conformational transitions, present an emerging strategy for developing lightweight and versatile smart materials. However, visible light‐triggered tailored guests capture and release behaviors in all‐organic solids are rarely reported. Here, we introduce a photoreactive crystalline boron‐nitrogen (B←N) host adduct with the ability to undergo [2+2] photocycloaddition upon 447 nm light exposure. This process facilitates single‐crystal‐to‐single‐crystal (SCSC) photodimerization in the mother liquor, maintaining the original B←N host structure. Weakened intermolecular interactions within the photodimer host contribute to fast guest release in air under irradiation. Furthermore, the dynamic B←N bonds enable reversible transformations between organic host adducts and adduct cocrystals under the solvent‐induced allosteric effect. As a result, four B←N host adduct crystals containing individual alkane guest are easily obtained and exhibited the ability of photo‐controlled alkane release. Therefore, the integration of photo reactivity and structural transformation within B←N host adduct enables customized capture and release of guest molecules.

Responsive Supramolecular Nanomicelles Formed through Self-Assembly of Acyclic Cucurbit[n]uril for Targeted Drug Delivery to Cancer Cells.

The supramolecular drug delivery systems (SDDSs) based on host-guest recognition through noncovalent interactions, capable of responsive behavior and dynamic switching to external stimuli, have attracted considerable attention in cancer therapy. In this study, a targeted dual-functional drug delivery system was designed and synthesized. A hydrophilic macrocyclic host molecule (acyclic cucurbit[n]uril ACB) was modified with folic acid (FA) as a targeting ligand. The guest molecule consists of a disulfide bond attached to adamantane (DA) and cannabidiol (CBD) at both ends of the response element of glutathione. Recognition and self-assembly of host and guest molecules successfully functionalize supramolecular nanomicelles (SNMs), targeting cancer cells and releasing drugs in a high glutathione environment. The interactions between host and guest molecules were investigated by using nuclear magnetic resonance (NMR), fluorescence titration, Fourier-transform infrared spectroscopy (FT-IR), and thermal analysis (TGA). Transmission electron microscopy (TEM) and dynamic light scattering (DLS) confirmed the nanostructure of the SNMs. Experimentation with 5,5'-dithiobis (2-nitrobenzoic acid) (DTNB) demonstrated the responsiveness of SNMs to glutathione (GSH). In vitro cytotoxicity assays demonstrated that SNMs had a greater targeting efficacy for four types of cancer cells (HeLa, HCT-116, A549, and HepG2) compared to normal 293T cells. Cellular uptake studies revealed that HeLa cells more readily absorbed SNMs, leading to their accumulation in the tumor cell cytoplasm. Fluorescence colocalization assays verified that SNMs efficiently accumulated in organelles related to energy metabolism and signaling, including mitochondria and the endoplasmic reticulum, affecting cellular metabolic death. Both flow cytometry and confocal nuclear staining assays confirmed that SNMs effectively induced apoptosis over time, ultimately resulting in the death of cancer cells. These findings demonstrate that SNMs exhibit excellent targeting ability, responsiveness, high bioavailability, and stability, suggesting significant potential in drug delivery applications.

Bjerrum defects in s-II gas hydrate

The energy and structure of Bjerrum defects in structure II gas hydrates were investigated by using first-principle calculations for finite-size clusters and periodic 3D lattice systems. The formation energies of these defects were calculated for the first time when the cages of the structure II structure were completely empty and the large cage was filled with a THF molecule. Analogous to findings in ice structures, one of the hydrogen atoms forming the D defect was noted to orient toward the cage. If the excess proton resides in the large cage, it acts as an attraction center for the polar guest molecule, i.e., THF. Therefore, the large cage guest THF molecule stabilizes the D/L defect pair and isolated D/L defect formation energies by forming hydrogen bonds with the D defect. In such cases, the defect structure representing a D/L defect pair containing a THF molecule interacting with one of the hydrogen atoms of the D defect mirrors the guest-induced ones. Notably, the classical Bjerrum defect and the guest-induced Bjerrum defect exhibit a similar phenomenon in defective structures. Contrary to existing literature, it is evident that guest-induced Bjerrum defects involve both the L and D components. The insights gained from this study could potentially offer an alternative perspective to understand various experimental observations, such as those related to dielectric and NMR properties.

Magnesium-Induced Rapid Nucleation of Tetrahydrofuran Hydrates.

Hydrates are ice-like crystalline structures of hydrogen-bonded water molecules that trap a guest molecule. Hydrates have several applications, including carbon sequestration, gas separation, desalination, etc. A classical major challenge associated with artificial hydrate formation is the very long induction time to nucleate hydrates. This has spurred the development of multiple chemical, mechanical, and electrical strategies to promote nucleation. Presently, we discover that magnesium can significantly promote the nucleation of tetrahydrofuran (THF) hydrates. While magnesium has been recently shown (by our group) to promote the formation of carbon dioxide hydrates (gas-liquid system), this study discovers that the benefits of magnesium extend to liquid-liquid hydrate systems as well. Experiments show that magnesium reduces the induction time for THF hydrate nucleation with deionized (DI) water and saltwater by six and eight times, respectively. Magnesium-induced nucleation rate enhancements for hydrate formation with DI water and saltwater were 12 and 99 times, respectively. Importantly, we demonstrate near-instantaneous nucleation when magnesium is introduced after the hydrate-forming system reaches suitable thermodynamic conditions. We conduct statistically significant measurements of nucleation and XPS analysis to identify the underlying mechanisms responsible for nucleation. We discuss multiple phenomena at play, including chemical and mechanistic promotion pathways. The formation of hydrogen bubbles and the presence of magnesium ions in solution are seen as important to magnesium-based nucleation promotion. Importantly, very low amounts of Mg are consumed in this process unlike in traditional chemical promotion techniques. Overall, our discovery can enable on-demand nucleation of liquid-liquid hydrate systems, which is critical to the development of several applications.

Oriented 1D Metal-Organic Frameworks for Selective Chemisorption by a Substitution-Insertion Mechanism.

Chemisorption on organometallic-based adsorbents is crucial for the controlled separation and purification of targeted systems. Herein, oriented 1D NH2-CuBDC·H2O metal-organic frameworks (MOFs) featuring accessible CuII sites are successfully fabricated by bottom-up interfacial polymerization. The prepared MOFs, as deliberately self-assembled secondary particles, exhibit a visually detectable coordination-responsive characteristic induced by the nucleophilic substitution and competitive coordination of guest molecules. As a versatile phase-change chemosorbent, the MOFs exhibit unprecedented NH3 capture (18.83 mmol g-1 at 298 K) and bioethanol dehydration performance (enriching ethanol from 99% to 99.99% within 10 min by direct adsorption separation of liquid mixtures of ethanol and water). Furthermore, the raw materials for preparing the 1D MOFs are inexpensive and readily available, and the facile regeneration with water washing at room temperature effectively minimizes the energy consumption and cost of recycling, enabling it to be the most valuable adsorbent for the removal and separation of target substances.

Synthesis and characterization of self-healable supramolecular hydrogel based on carboxymethyl cellulose for biomedical applications

Hydrogels have been widely used in biomedical fields including tissue engineering, drug delivery and cell delivery and 3D cell delivery due to abundant water content in their hydrophilic three-dimensional networks and having soft tissue similar to the human body. In recent years, supramolecular hydrogels (SHG) formed by the inclusion complex between polyethylene glycol (PEG) and macrocycles such as cyclodextrin (CD) have attracted much interest due to their excellent biocompatibility and great potential in biomedical. In this research, a carboxymethyl cellulose (CMC)-based graft copolymer was prepared by using acrylic acid (AA) and maleic anhydride functionalized β-CD (β-CD-MA) as comonomers and ammonium persulfate (APS) as initiator. Then, a self-healable supramolecular hydrogel was synthesized by formation of a host-guest inclusion complex between CMC-g-poly (AA-co-β-CD-MA) as host molecule and cytosine- and guanine-modified PEG as guest molecules. The prepared hydrogel was characterized by Scanning Electron Microscope (SEM), X-Ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), Nuclear magnetic resonance spectroscopy (1H NMR). The thermal stability of hydrogel was also determined by thermal gravimetric (TGA) and differential scanning calorimetry (DSC) methods. In addition, the loading and release profiles of metformin hydrochloride (MH) drug as a model on hydrogel was investigated. The results indicated that the drug release from the hydrogel peaks around 360 min and aligns with the Ritger-Peppas model. The hydrogel's self-healing property was examined at ambient temperature and 37 °C. It showed 70 % healing in 1.5 h and completed recovery after 9 h.

Ternary composite fluorescent films with tunable color and long lifetime based on efficient TS-FRET

Multi-color long-wavelength organic afterglow materials are of great significance in anti-counterfeiting, but their preparation is still challenging. In this paper, a series of room temperature phosphorescence (RTP) films were constructed with polyvinyl alcohol (PVA) as rigid matrix and 9,10-diaminophenanthrene (DAphe) as guest molecule. Surprisingly, by adjusting the doping content of DAphe, their RTP emission peak width could be adjusted accordingly, and the lifetime was up to 3.25 s. Their dopant content dependent and excitation wavelength dependent luminescence characteristics and theoretical calculation results indicated that the observed broad emission peaks of RTP might be attributed to multiple luminescence centers generated by the aggregation of guest molecules. Interestingly, by doping several suitable fluorescent dyes screened as energy acceptors, multi-color, long-lasting afterglow composite films from blue to red were obtained, achieving 0.42 s delayed fluorescence at 661 nm with a fluorescence quantum yield of 32.22 %. In addition, these adjustable afterglow materials had good molding processability, so several cryptographic patterns were achieved to demonstrate their good application prospects in advanced anti-counterfeiting technologies.

Exploring the interaction between derivatives of urea with resorcinol-based acridinedione dyes by employing fluorescence methods and molecular docking approach

Akyl urea derivatives, either symmetrical or unsymmetrical in nature possessing a free N-H or N-alkyl moieties in the molecular framework of urea governs the excited state properties of acridinedione dye (ADR1) which is a resorcinol-based derivative. Fluorescence enhancement (FE) of ADR1 dye is observed on the addition of unsymmetrical urea derivatives, whereas a decrease in the fluorescence intensity resulted upon the addition of symmetrical urea derivatives. The nature of the urea derivatives controls the suppression of photoinduced electron transfer (PET) via space, which is the cause of the FE. FQ results from the donor and acceptor moieties of ADR1 dye promoting the PET process. Urea (U), symmetrical and unsymmetrical urea derivatives (except Tetramethyl urea (TMU)) results no significant shift of the localized excited (LE) state emission of ADR1 dye. Studies of the ADR1 dye’s fluorescence lifetime in the presence of urea compounds show a significant increase in lifetime. This phenomenon is explained by a significant difference in the hydrogen-bonding (HB) pattern, which causes variationin the microenvironment created by thesolute molecules in the aqueous phase. Both the hydrophobic effects of the alkyl group substituents in the urea molecular framework and the HB interactions between the solute and solvent influence the excited state features of ADR1 dye. Further, the role of urea derivatives and ADR1 dye (both are considered as competitive guest molecules) energetics and molecular interactions were studied in the presence of host molecule, Human Serum Albumin (HSA). The binding energy (BE) and several bimolecular interactions driven by urea derivatives in the presence of ADR1-HSA complex in comparison with that of urea derivatives-HSA complex were investigated by molecular docking (Mol.Doc) methodology. Incorporating theoretical research along withsteady state and time-resolved fluorescence investigations proved to be an effective method to evaluate the interactions of competing solutes comprising bothhydrophobic and HB functional groups.

Microscopic study on the memory effect of methane hydrate in the presence of silica nanoparticles: Ⅰ. Dissociation mechanism & guest supersaturated hypothesis

As a key issue emerged in the exploitation of combustible ice resources, the memory effect inducing hydrate reformation in sand-containing dissociated-water system is still ambiguous. Among them, methane hydrate dissociation kinetics and guest supersaturated hypothesis for methane hydrate reformation are the primary issues to be addressed. A molecular dynamics simulation system where methane hydrate interacts with surface-hydroxylated silica nanoparticles was established to simulate dissociation process, which is necessary to construct hydrate reformation systems for further microscopic study on hydrate memory effect. The transportation mechanism of methane during hydrate dissociation in sand-containing aqueous system was elucidated. Based on this, hydrate-dissociated systems with methane supersaturated were captured, and molecular dynamics simulations were carried out to further study hydrate reformation mechanism regarding the guest supersaturated hypothesis. By analyzing the distribution and transportation of methane, hydrate clusters, and silica nanoparticles, it can be concluded that the hydrate-like orderly arrangement of methane that are dissolved in the solution or on the surface of nanobubbles are necessary to trigger hydrate memory effect by inducing the reformation of hydrate clusters, while the silica nanoparticles can inhibit the reformation of hydrate clusters by disturbing the arrangement of methane molecules and water molecules. Thence, the microscopic analysis indicated that supersaturated guest molecules is vital to the occurrence of hydrate memory effect and its effect varies between the supersaturated states.