Chemical Interactions Research Articles

Self-Assembled Hydrogel Membranes with Structurally Tunable Mechanical and Biological Properties.

Using supramolecular self-assembled nanocomposite materials made from protein and polysaccharide components is becoming more popular because of their unique properties, such as biodegradability, hierarchical structures, and tunable multifunctionality. However, the fabrication of these materials in a reproducible way remains a challenge. This study presents a new evaporation-induced self-assembly method producing layered hydrogel membranes (LHMs) using tropocollagen grafted by partially deacetylated chitin nanocrystals (CO-g-ChNCs). ChNCs help stabilize tropocollagen's helical conformation and fibrillar structure by forming a hierarchical microstructure through chemical and physical interactions. The LHMs show improved mechanical properties, cytocompatibility, and the ability to control drug release using octenidine dihydrochloride (OCT) as a drug model. Because of the high synergetic performance between CO and ChNCs, the modulus, strength, and toughness increased significantly compared to native CO. The biocompatibility of LHM was tested using the normal human dermal fibroblast (NHDF) and the human osteosarcoma cell line (Saos-2). Cytocompatibility and cell adhesion improved with the introduction of ChNCs. The extracted ChNCs are used as a reinforcing nanofiller to enhance the performance properties of tropocollagen hydrogel membranes and provide new insights into the design of novel LHMs that could be used for various medical applications, such as control of drug release in the skin and bone tissue regeneration.

An Alkyne-bridged Covalent Organic Framework Featuring Interactive Pockets for Bromine Capture.

The high degree of corrosivity and reactivity of bromine, which is released from various sources poses a serious threat to the environment. Moreover, its coexistence with iodine forming an equilibrium compound, iodine monobromide (IBr) necessitates the selective capture of bromine from halogen mixtures. The electrophilicity of halogens to π-electron rich structures enabled us to strategically design a covalent organic framework for halogen capture, featuring a defined pore environment with localized sorption sites. The higher capture capacity of bromine (4.6gg-1) over iodine by ~41% shows its potential in selective capture. Spectroscopic results uncovering the preferential interaction sites are supported by theoretical investigations. The alkyne bridge is a core functionality promoting the selectivity in capture by synergistic physisorption, rationalized by the higher orbital overlap of bromine due to its smaller atomic size as well as reversible chemical interactions. The slip stacking in the structure has further promoted this phenomenon by creating clusters of molecular interaction sites with bromine intercalated between the layers. The inclusion of unsaturated moieties, i.e. triple bonds and the complementary pore geometry offer a promising design strategy for the construction of porous materials for halogen capture.

An Alkyne‐bridged Covalent Organic Framework Featuring Interactive Pockets for Bromine Capture

The high degree of corrosivity and reactivity of bromine, which is released from various sources poses a serious threat to the environment. Moreover, its coexistence with iodine forming an equilibrium compound, iodine monobromide (IBr) necessitates the selective capture of bromine from halogen mixtures. The electrophilicity of halogens to π‐electron rich structures enabled us to strategically design a covalent organic framework for halogen capture, featuring a defined pore environment with localized sorption sites. The higher capture capacity of bromine (4.6 g g‐1) over iodine by ~41 % shows its potential in selective capture. Spectroscopic results uncovering the preferential interaction sites are supported by theoretical investigations. The alkyne bridge is a core functionality promoting the selectivity in capture by synergistic physisorption, rationalized by the higher orbital overlap of bromine due to its smaller atomic size as well as reversible chemical interactions. The slip stacking in the structure has further promoted this phenomenon by creating clusters of molecular interaction sites with bromine intercalated between the layers. The inclusion of unsaturated moieties, i.e. triple bonds and the complementary pore geometry offer a promising design strategy for the construction of porous materials for halogen capture.

Coordination Defect‐Induced Lewis Pairs in Metal−Organic Frameworks Boosted Sulfur Kinetics for Bifunctional Photo‐Assisted Li−S Batteries

AbstractThe photo‐assisted strategy is regarded as a crucial approach to enhance the conversion kinetics of polysulfides in lithium–sulfur (Li–S) batteries. However, the development of photo‐assisted Li–S batteries still faces important challenges, such as the rapid recombination of photogenerated electron−holes on cathode and more severe shuttle effect. Herein, a breakthrough in overcoming the challenges has been made by constructing a promising photo‐assisted Li−S battery based on semiconducted metal−organic frameworks. During the discharging progress, the photoexcited electrons generated by H2BPDC ligand based on ligand‐to‐metal charge transfer (LMCT) effect, are injected into the Ti‐oxo clusters in Ti‐MOF, thereby facilitating the sulfur reduction to Li2S. And photoexcited holes are capable of promoting the decomposition kinetics of Li2S during charging. More importantly, the stronger chemical interaction between Ti‐BPDC‐d and polysulfides under light inhibits the polysulfides dissolution and shuttling, which fundamentally addresses the issue of light‐accelerated shuttling. As a result, the photo‐assisted Li–S batteries deliver a reversible capability of 1090.21 mAh g−1 at 0.2 C with a capacity retention of 82.91% over 150 cycles, and a superior rate capability of 673.58 mAh g−1 at 5 C. The findings are promising in advancing the design principles for photo‐rechargeable Li−S batteries.

Resist Thermal Shock Through Viscoelastic Interface Encapsulation in Perovskite Solar Cells

Enhancing the lifetime of perovskite solar cells (PSCs) is one of the essential challenges for their industrialization. Although the external encapsulation protects the perovskite device from the erosion of moisture and oxygen under various harsh conditions. However, the perovskite devices still undergo static and dynamic thermal stress during thermal and thermal cycling aging, respectively, resulting in irreversible damage to the morphology, component, and phase of stacked materials. Herein, the viscoelastic polymer polyvinyl butyral (PVB) material is designed onto the surface of perovskite films to form flexible interface encapsulation. After PVB interface encapsulation, the surface modulus of perovskite films decreases by nearly 50%, and the interface stress range under the dynamic temperature field (−40 to 85 °C) drops from −42.5 to 64.8 MPa to −14.8 to 5.0 MPa. Besides, PVB forms chemical interactions with FA+ cations and Pb2+, and the macroscopic residual stress is regulated and defects are reduced of the PVB encapsulated perovskite film. As a result, the optimized device's efficiency increases from 22.21% to 23.11%. Additionally, after 1500 h of thermal treatment (85 °C), 1000 h of damp heat test (85 °C & 85% RH), and 250 cycles of thermal cycling test (−40 to 85 °C), the devices maintain 92.6%, 85.8%, and 96.1% of their initial efficiencies, respectively.

Controlled Growth Lateral/Vertical Heterostructure Interface for Lithium Storage.

Artificial heterostructures with structural advancements and customizable electronic interfaces are fundamental for achieving high-performance lithium-ion batteries (LIBs). Here, we propose a design idea for a covalently bonded lateral/vertical black phosphorus (BP)-graphdiyne oxide (GDYO) heterostructure achieved through a facile ball-milling approach. Lateral heterogeneity is realized by the sp2-hybridized mode P-C bonds, which connects the phosphorus atoms at the edges of BP with the carbon atoms of the terminal acetylene in GDYO. The vertical connection of the heterojunction of BP and GDYO is connected by P-O-C bond. Experimental and theoretical studies demonstrate that BP-GDYO incorporates interfacial and structural engineering features, including built-in electric fields, chemical bond interactions, and maximized nanospace confinement effects. Therefore, BP-GDYO exhibits improved electrochemical kinetics and enhanced structural stability. Moreover, through ex- and in-situ studies, we clarified the lithiation mechanism of BP-GDYO, highlighting that the introduction of GDYO inhibits the shuttle/dissolution effect of phosphorus intermediates, hinders volume expansion, provides more reactive sites, and ultimately promotes reversible lithium storage. The BP-GDYO anode exhibits lithium storage performance with high-rate capacity and long-cycle stability (602.6 mAh g-1 after 1000 cycles at 2.0 A g-1). The proposed interfacial and structural engineering are universal and represents a conceptual advance in building high-performance LIBs electrode. This article is protected by copyright. All rights reserved.

Use of Alkaline-Activated Energy Waste Raw Materials in Geopolymer Concrete

Silica fly ash, Certyd aggregate, and an alkaline solution were used to produce lightweight geopolymer concretes. The compressive strength, water absorption, and bulk density results, along with SEM photos showing the structure of the obtained composite, were obtained. Tests conducted on the specifications of lightweight geopolymer concretes have revealed significant chemical interactions between the ash aggregate and the geopolymer mortar, particularly when the coarse aggregate surface has been pre-treated with an alkaline solution. A statistical analysis of the experimental data, which investigated the influence of three key variables on the compressive strength, water absorption, and bulk density of lightweight geopolymer concrete (LBG), identified the following factors as having the most substantial impact: the quantity of alkali used, the curing temperature, and the concentration of alkali in the mixture. The optimal test series exhibited a commendable compressive strength of 20.14 megapascals (MPa), accompanied by a water absorption rate of 14.72%, and a bulk density of 1486.6 kg per cubic meter (kg/m³). These findings underscore the importance of alkali content, curing temperature, and alkali concentration in tailoring the properties of lightweight geopolymer concrete to meet specific performance requirements.

Formulation development, characterization, and evaluation of bedaquiline fumarate – Soluplus® – solid dispersion

Bedaquiline fumarate (BQF) is classified as a BCS class II drug and has poor water solubility and dissolution rate, which ultimately compromises bioavailability. The objective of this study is to improve the biopharmaceutical properties of BQF through a solid dispersion system by using Soluplus®. Two solid dispersion systems were prepared i.e. binary solid dispersion (BSD) and ternary solid dispersion (TSD) where 14.31-fold and 20.43-fold increase in solubility of BQF was observed with BSD and TSD in comparison to BQF. In our previous research work, we explored the BSD and TSD of BQF with a crystalline polymer, poloxamer 188, which showed an increment in the solubility of BQF. In the current research, amorphous Soluplus® polymer was selected to formulate BSD and TSD with BQF and showed higher solubility than poloxamer 188. The various solid and liquid state characterization results confirmed the presence of an amorphous form of BQF inside solid dispersion. The Fourier transform infrared spectroscopy showed no chemical interactions between BQF and polymer. The cellular uptake results demonstrated higher uptake in Caco-2 cell lines. Pharmacokinetic studies showed enhanced solubility and bioavailability of TSDs. Hence, the present research shows a promising formulation strategy for enhancing the biopharmaceutical performance of BQF by increasing its solubility.

Self-assembly of nanocrystal checkerboard patterns via non-specific interactions

Checkerboard lattices—where the resulting structure is open, porous, and highly symmetric—are difficult to create by self-assembly. Synthetic systems that adopt such structures typically rely on shape complementarity and site-specific chemical interactions that are only available to biomolecular systems (e.g., protein, DNA). Here we show the assembly of checkerboard lattices from colloidal nanocrystals that harness the effects of multiple, coupled physical forces at disparate length scales (interfacial, interparticle, and intermolecular) and that do not rely on chemical binding. Colloidal Ag nanocubes were bi-functionalized with mixtures of hydrophilic and hydrophobic surface ligands and subsequently assembled at an air–water interface. Using feedback between molecular dynamics simulations and interfacial assembly experiments, we achieve a periodic checkerboard mesostructure that represents a tiny fraction of the phase space associated with the polymer-grafted nanocrystals used in these experiments. In a broader context, this work expands our knowledge of non-specific nanocrystal interactions and presents a computation-guided strategy for designing self-assembling materials.

Neutron scattering and neural-network quantum molecular dynamics investigation of the vibrations of ammonia along the solid-to-liquid transition

Vibrational spectroscopy allows us to understand complex physical and chemical interactions of molecular crystals and liquids such as ammonia, which has recently emerged as a strong hydrogen fuel candidate to support a sustainable society. We report inelastic neutron scattering measurement of vibrational properties of ammonia along the solid-to-liquid phase transition with high enough resolution for direct comparisons to ab-initio simulations. Theoretical analysis reveals the essential role of nuclear quantum effects (NQEs) for correctly describing the intermolecular spectrum as well as high energy intramolecular N-H stretching modes. This is achieved by training neural network models using ab-initio path-integral molecular dynamics (PIMD) simulations, thereby encompassing large spatiotemporal trajectories required to resolve low energy dynamics while retaining NQEs. Our results not only establish the role of NQEs in ammonia but also provide general computational frameworks to study complex molecular systems with NQEs.

Terrestrial Ecosystem Model in R (TEMIR) version 1.0: simulating ecophysiological responses of vegetation to atmospheric chemical and meteorological changes

Abstract. The newly developed offline land ecosystem model Terrestrial Ecosystem Model in R (TEMIR) version 1.0 is described here. This version of the model simulates plant ecophysiological (e.g., photosynthetic and stomatal) responses to varying meteorological conditions and concentrations of CO2 and ground-level ozone (O3) based on prescribed meteorological and atmospheric chemical inputs from various sources. Driven by the same meteorological data used in the GEOS-Chem chemical transport model, this allows asynchronously coupled experiments with GEOS-Chem simulations with unique coherency for investigating biosphere–atmosphere chemical interactions. TEMIR agrees well with FLUXNET site-level gross primary productivity (GPP) in terms of both the diurnal and monthly cycles (correlation coefficients R2>0.85 and R2>0.8, respectively) for most plant functional types (PFTs). Grass and shrub PFTs have larger biases due to generic model representations. The model performs best when driven by local site-level meteorology rather than reanalyzed gridded meteorology. Simulation using gridded meteorology agrees well for annual GPP in seasonality and spatial distribution with a global average of 134 Pg C yr−1. Application of Monin–Obukhov similarity theory to infer canopy conditions from gridded meteorology does not improve model performance, predicting an increase of +7 % in global GPP. Present-day O3 concentrations simulated by GEOS-Chem and an O3 damage scheme at high sensitivity show a 2 % reduction in global GPP with prominent reductions of up to 15 % in eastern China and the eastern USA. Regional correlations are generally unchanged when O3 is present and biases are reduced, especially for regions with high O3 damage. An increase in atmospheric CO2 concentration of 20 ppmv from the level in 2000 to the level in 2010 modestly decreases O3 damage due to reduced stomatal uptake, consistent with ecophysiological understanding. Our work showcases the utility of this version of TEMIR for evaluating biogeophysical responses of vegetation to changes in atmospheric composition and meteorological conditions.

Statistical Design and Optimization of Nano-Transfersomes Based Chitosan Gel for Transdermal Delivery of Cefepime

Objectives: This research aimed to overcome challenges posed by cefepime excessive elimination rate and poor patient compliance by developing transdermal delivery system using nano-transfersomes based chitosan gel. Methods: Rotary evaporation-sonication method and the Box-Behnken model were used to prepare cefepime loaded nano-transfersomes (CPE-NTFs). The physiochemical characterization of CPE-NTFs were analyzed including DLS, deformability index, DSC and antimicrobial study. Optimized CPE-NTFs loaded into chitosan gel and appropriately characterized. In vitro release, ex vivo and in vivo studies were performed. Results: The CPE-NTFs were physically stable with particle size 222.6 ± 1.8 nm, polydispersity index 0.163 ± 0.02, zeta potential -20.8 ± 0.1 mv, entrapment efficiency 81.4 ± 1.1% and deformability index 71 ± 0.2. DSC analysis confirmed successful drug loading and thermal stability. FTIR analysis showed no chemical interaction among the excipients of CPE-NTFs gel. The antibacterial activity demonstrated a remarkable reduction in the minimum inhibitory concentration of cefepime when incorporated into nano-transfersomes. CPE-NTFs based chitosan gel (CPE-NTFs gel) showed significant physicochemical properties. In vitro release studies exhibited sustained release behavior over 24 hours, and ex vivo studies indicated enhanced permeation and retention compared to conventional cefepime gel. In vivo skin irritation studies confirmed CPE-NTFs gel was non-irritating and biocompatible for transdermal delivery. Conclusion: This research showed nano-transfersomes-based chitosan gel is a promising approach for cefepime transdermal delivery and provides sustained release of cefepime.

Direct Observation of Enhanced Iodine Binding within a Series of Functionalized Metal-Organic Frameworks with Exceptional Irradiation Stability.

Optimization of active sites and stability under irradiation are important targets for sorbent materials that might be used for iodine (I2) storage. Herein, we report the direct observation of I2 binding in a series of Cu(II)-based isostructural metal-organic frameworks, MFM-170, MFM-172, MFM-174, NJU-Bai20, and NJU-Bai21, incorporating various functional groups (-H, -CH3, - NH2, -C≡C-, and -CONH-, respectively). MFM-170 shows a reversible uptake of 3.37 g g-1 and a high packing density of 4.41 g cm-3 for physiosorbed I2. The incorporation of -NH2 and -C≡C- moieties in MFM-174 and NJU-Bai20, respectively, enhances the binding of I2, affording uptakes of up to 3.91 g g-1. In addition, an exceptional I2 packing density of 4.83 g cm-3 is achieved in MFM-174, comparable to that of solid iodine (4.93 g cm-3). In situ crystallographic studies show the formation of a range of supramolecular and chemical interactions [I···N, I···H2N] and [I···C≡C, I-C═C-I] between -NH2, -C≡C- sites, respectively, and adsorbed I2 molecules. These observations have been confirmed via a combination of solid-state nuclear magnetic resonance, X-ray photoelectron, and Raman spectroscopies. Importantly, γ-irradiation confirmed the ultraresistance of MFM-170, MFM-174, and NJU-Bai20 suggesting their potential as efficient sorbents for cleanup of radioactive waste.

Adsorption and sensing characteristics of insulating gas C4F7N on 3d late transition metal‐phthalocyanine: Theoretical and experimental study

AbstractHeptafluoroisobutyronitrile (C4F7N) is being considered as a promising alternative to the greenhouse gas SF6 in the electrical industry. However, its biotoxicity necessitates the development of gas sensing technology to detect leaked C4F7N. A combination of density functional theory and experiments was employed to evaluate the adsorption and sensing performance of different metal‐phthalocyanines as potential sensing materials for C4F7N detection. The study included exploring adsorption configurations with adsorption energies, electron transfer, and adsorption distance, as well as comparisons of electronic properties, electron distribution, and density of states (DOS) among the MPcs. Furthermore, gas sensing experiments were conducted using different MPcs to detect 25–100 ppm C4F7N. The results revealed that Mn‐Pc, Fe‐Pc, Co‐Pc, and Zn‐Pc exhibited considerable chemical interactions, while Ni‐Pc and Cu‐Pc showed weaker adsorption strength. These findings were further elucidated based on the electron density and DOS of atomic orbitals. Moreover, gas sensing experiments indicated that Co‐Pc demonstrated a higher response compared to Fe‐Pc at the same concentration of C4F7N. Overall, the theoretical and experimental insights offer valuable guidance for C4F7N detection and provide a systematic approach to screen and explore organometallic polymer‐based gas sensors applicable in various fields.

Properties of polylactic acid/gelatin/acetyl tributyl citrate blend materials

AbstractThe inherent brittleness and high cost of polylactic acid (PLA) hinder its further application. Developing low‐cost, flexible, and biodegradable gelatin (GEL)‐modified PLA is a way to broaden the application prospects of PLA applications. Acetyl tributyl citrate (ATBC) was added to overcome the process difficulty of PLA/GEL melt blending and toughening the blends. Maleic anhydride (MAH) grafted PLA (PLA‐g‐MAH) was prepared to improve the compatibility of the PLA/GEL/ATBC. Because of the interface, physical and chemical interaction induced by PLA‐g‐MAH, the compatibility among PLA, GEL, and ATBC was enhanced, which significantly improved the plasticizing efficiency of ATBC. Results showed that the elongation at break of the blends can be improved by 491%, 68 times higher than that of pristine PLA. Moreover, the modified blends did not break under the conditions of notch impact, which exhibited excellent toughness. The blends possessed a high degradation rate owing to the hydrophilic gelatin and PLA‐g‐MAH, significantly accelerated the degradation process of PLA. The prepared PLA/GEL/ATBC/PLA‐g‐MAH biomass blended plastics exhibited good comprehensive performance, with true sustainability and environmental friendliness.

Anionic Effects on Concentrated Aqueous Lithium Ion Dynamics.

The dynamics, orientational anisotropy, diffusivity, viscosity, and density were measured for concentrated lithium salt solutions, including lithium chloride (LiCl), lithium bromide (LiBr), lithium nitrite (LiNO2), and lithium nitrate (LiNO3), with methyl thiocyanate as an infrared vibrational probe molecule, using two-dimensional infrared spectroscopy (2D IR), nuclear magnetic resonance (NMR) spectroscopy, and viscometry. The 2D IR, NMR, and viscosity results show that LiNO2 exhibits longer correlation times, lower diffusivity, and nearly 4 times greater viscosity compared to those of the other lithium salt solutions of the same concentration, suggesting that nitrite anions may strongly facilitate structure formation via strengthening water-ion network interactions, directly impacting bulk solution properties at sufficiently high concentrations. Additionally, the LiNO2 and LiNO3 solutions show significantly weakened chemical interactions between the lithium cations and the methyl thiocyanate when compared with those of the lithium halide salts.

Compatibility study of mirtazapine with several excipients used in pharmaceutical dosage forms employing thermal and non-thermal methods

AbstractMirtazapine is an atypical antidepressant used in the management of insomnia, post-traumatic stress disorder, anxiety or panic disorder, obsessive–compulsive disorder and migraines. It is used worldwide in pharmaceutical formulations alongside various excipients in its hemihydrate form. The objective of the study was the compatibility evaluation between MRTHH and ten pharmaceutical excipients. The presence of incompatibilities between the API and the selected excipients was evaluated using Fourier transform infrared spectroscopy performed on all pure samples and prepared mixtures at room temperature (23 ± 2 °C), as well as a complete thermal stress evaluation (TG—thermogravimetric/DTG—derivative thermogravimetric/DSC—differential scanning calorimetry). The results showed particularities for all analyzed mixtures, α-lactose monohydrate, starch, sorbitol, magnesium stearate, calcium lactate and magnesium citrate proving to be safe to use together with mirtazapine in binary mixtures at temperatures below 130 °C, while for polyvinylpyrrolidone K30 and aerosol precautions need to be considered at temperatures over 100 °C. The association of mirtazapine with D-mannitol or stearic acid proved to raise concerns even at room temperature, indicating possible interactions that may alter the chemical integrity of the active pharmaceutical ingredient and with it, its therapeutic effect. These findings should be taken into consideration during the selection of the technological procedures used in the manufacturing process of dosage forms that include mirtazapine alongside with any of these excipients so that unwanted chemical interactions could be avoided.

Evaluation of a novel depressant PMAA for the separation of fluorite from calcite using NaOl as a collector

It is challenging to separate fluorite from calcite due to their same calcium activated sites on their surfaces. The copolymer of maleic and acylic acid (PMAA) was used to inhibit the calcite in the flotation of fluorite. Micro-flotation results exhibited that sodium oleate (NaOl) had a good ability to collect fluorite and calcite in the scope of pH 7-10. The PMAA treatment prior to NaOl selectively depressed the floatability of calcite while allowed the flotation of fluorite, and the artificial minerals mixture plotted that fluorite/calcite could be effectively separated in the presence of PMAA/NaOl. Zeta potential results suggested that NaOl collector was absorbed on the PMAA-conditioned calcite surface but did not adsorb on the PMAA-conditioned fluorite surface. XPS results and calculational chemistry revealed the chemical interaction occurred between calcite surface and PMAA which was attributed to the calcium ions of calcite surface interacting with -COOH group of PMAA.

Computer-Aided Drug Discovery Approaches in the Identification of Anticancer Drugs from Natural Products: A Review.

Natural plant sources are essential in the development of several anticancer drugs, such as vincristine, vinblastine, vinorelbine, docetaxel, paclitaxel, camptothecin, etoposide, and teniposide. However, various chemotherapies fail due to adverse reactions, drug resistance, and target specificity. Researchers are now focusing on developing drugs that use natural compounds to overcome these issues. These drugs can affect multiple targets, have reduced adverse effects, and are effective against several cancer types. Developing a new drug is a highly complex, expensive, and time-consuming process. Traditional drug discovery methods take up to 15 years for a new medicine to enter the market and cost more than one billion USD. However, recent Computer Aided Drug Discovery (CADD) advancements have changed this situation. This paper aims to comprehensively describe the different CADD approaches in identifying anticancer drugs from natural products. Data from various sources, including Science Direct, Elsevier, NCBI, and Web of Science, are used in this review. In-silico techniques and optimization algorithms can provide versatile solutions in drug discovery ventures. The structure-based drug design technique is widely used to understand chemical constituents' molecular-level interactions and identify hit leads. This review will discuss the concept of CADD, in-silico tools, virtual screening in drug discovery, and the concept of natural products as anticancer therapies. Representative examples of molecules identified will also be provided.

Probing the Interaction Between Biomolecules Under Sub-Zero Temperature Conditions by Electrophoresis in Ice Grain Boundaries

BackgroundPsychrophiles can survive under cryogenic conditions because of various biomolecules. These molecules interact with cells, ice crystals, and lipid bilayers to enhance their functionality. Previous studies typically measured these interactions by thawing frozen samples and conducting biological assays at room temperature; however, studying these interactions under cryogenic conditions is crucial. This is because these biomolecules can function at lower temperatures. Therefore, a platform for measuring chemical interactions under sub-zero temperature conditions must be established. ResultsThe chemical interactions between biomolecules under sub-zero temperature conditions were evaluated within ice grain boundaries with a channel-like structure, which circumvents the need for thawing. An aqueous solution of sucrose was frozen within a microfluidic channel, facilitating the formation of freeze-concentrated solutions (FCSs) that functioned as size-tunable electrophoretic fields. Avidin proteins or single-stranded DNA (ssDNA) were introduced into the FCS in advance. Probe micro/nanospheres whose surfaces were modified with molecules complementary to the target analytes were introduced into the FCS. If the targets have functionalities under sub-zero temperature conditions, they interact with complementary molecules. The chemical interactions between the target molecules and nanospheres led to the aggregation of the particles. The size tunability of the diameter of the FCS channels enabled the recognition of aggregation levels, which is indicative of interaction reactivity. The avidin–biotin interaction and ssDNA hybridization served as models for chemical interactions, demonstrating interactivity under sub-zero temperature conditions. The results presented herein suggest the potential for in situ measurement of biochemical assays in the frozen state, elucidating the functionality of bio-related macromolecules at or slightly below 0°C. SignificanceThis is the first methodology to evaluate chemical interactions under sub-zero temperature conditions without employing the freeze-and-thaw process. This method has the advantage of revealing the chemical interactions only at low temperatures. Therefore, it can be used to screen and evaluate the functionality of cryo-related biomolecules, including cold-shock and antifreeze proteins.