Conformational Structure Research Articles

Investigating Benzoic Acid Derivatives as Potential Atomic Layer Deposition Inhibitors Using Nanoscale Infrared Spectroscopy

Area-selective atomic layer deposition (AS-ALD) is a technique utilized for the fabrication of patterned thin films in the semiconductor industry due to its capability to produce uniform and conformal structures with control over thickness at the atomic scale level. In AS-ALD, surfaces are functionalized such that only specific locations exhibit ALD growth, thus leading to spatial selectivity. Self-assembled monolayers (SAMs) are commonly used as ALD inhibiting agents for AS-ALD. However, the choice of organic molecules as viable options for AS-ALD remains limited and the precise effects of ALD nucleation and exposure to ALD conditions on the structure of SAMs is yet to be fully understood. In this work, we investigate the potential of small molecule carboxylates as ALD inhibitors, namely benzoic acid and two of its derivatives, 4-trifluoromethyl benzoic acid (TBA), and 3,5-Bis (trifluoromethyl)benzoic acid (BTBA) and demonstrate that monolayers of all three molecules are viable options for applications in ALD blocking. We find that the fluorinated SAMs are better ALD inhibitors; however, this property arises not from the hydrophobicity but the coordination chemistry of the SAM. Using nanoscale infrared spectroscopy, we probe the buried monolayer interface to demonstrate that the distribution of carboxylate coordination states and their evolution is correlated with ALD growth, highlighting the importance of the interfacial chemistry in optimizing and assessing ALD inhibitors.

Structural Conformation and the Binding of Factor VIII R2159C (FVIII-Ise) Mutated in the C1 Domain to Phospholipid.

We previously identified a factor (F)VIII molecular defect associated with an R2159C mutation in the C1 domain (named "FVIII-Ise") together with undetectable FVIII antigen (FVIII:Ag) levels measured by two-site sandwich ELISA using an anti-C2 domain alloantibody (alloAb). The patient had clinically mild hemophilia A, and his reduced FVIII:C correlated with FVIII:Ag measured by ELISA using monoclonal antibodies (mAbs) with A2 and A2/B domain epitopes, suggesting that the R2159C mutation modified C2 domain antigenicity. To investigate functional and structural characteristics of the FVIII-R2159C mutant. ELISAs using a previous anti-C2 domain alloAb confirmed that the antigen level of recombinant FVIII-R2159C mutant prepared in BHK cells was 56% lower relative to wild-type (WT), consistent with our earlier reports. This anti-C2 domain alloAb competitively inhibited FVIII and anti-C1 domain mAb binding, indicating the involvement of specificity for C1 and C2 epitopes. The K m for FVIII-R2159C with FIXa or FX in the tenase complex was similar to that of FVIII-WT. Thrombin- and FXa-catalyzed cleavage reactions of FVIII-R2159C were similar to those of WT. The K d for FVIII-R2159C binding to phospholipids was moderately greater than for FVIII-WT, however, while there were no significant differences in von Willebrand factor binding. In silico molecular dynamic simulation analyses revealed subtle differences between FVIII-WT and FVIII-R2159C. The FVIII-R2159C mutation was not different from FVIII-WT in interactions with FIXa, FX, and thrombin, but reduced binding potential to phospholipids and to an anti-C1/C2 domain alloAb was evident apparently due to subtle changes in conformational structure.

Biosynthesis of 10-Hydroxy-2-Decenoic Acid in Escherichia coli.

10-hydroxy-2-decenoic acid (10-HDA), a unique unsaturated fatty acid present in royal jelly, has attracted considerable interest due to its potential medical applications. However, its low concentration in royal jelly and complex conformational structure present challenges for large-scale production. In this study, we designed and constructed a de novo biosynthetic pathway for 10-HDA in Escherichia coli. Initially, we introduced the heterologous thioesterase UaFatB1 to hydrolyze trans-2-decenoyl ACP to produce trans-2-decenoic acid, a key precursor for 10-HDA. Subsequently, we employed the bacterial cytochrome P450 enzyme CYP153AMaq to catalyze the terminal hydroxylation of trans-2-decenoic acid. Furthermore, through redox partner engineering and directed evolution, we identified the optimal combination for 10-HDA production: CYP153AMaq Q129R/V141L mutant with redox partner FdR0978/Fdx0338. Finally, we optimized the fermentation conditions and achieved a 10-HDA titer of 18.8 mg/L using glucose as primary carbon source. Our work establishes a platform for producing α,β-unsaturated fatty acids and its derivatives, facilitating more study of these compounds.

Revealing the Solution Conformation and Hydration Structure of Type I Tropocollagen Using X-ray Scattering and Molecular Dynamics Simulation.

Hydration plays a crucial role in regulating the dispersion behavior of biomolecules in water, particularly in how pH-sensitive hydration water network forms around proteins. This study explores the conformation and hydration structure of Type-I tropocollagen using small- and wide-angle X-ray scattering (SWAXS) and molecular dynamics (MD) simulations. The results reveal that tropocollagen exhibits a significant softening conformation in solution, transitioning from its rod-like structure in tissues to a worm-like conformation, characterized by a reduced radius of gyration of 50 nm and a persistent length of 34 nm. The SWAXS-supported MD calculations further establish a hydration water network characterized by a 2.8 Å free-water exclusion zone where water molecules are largely hydrogen-bonded to the densely distributed polar groups on the tropocollagen surfaces. These first-layer water molecules are bridged by outer water molecules extending up to 4 Å from the protein surfaces, forming a major hydration shell that encapsulates the protein.

On the substrate turnover rate of NBCe1 and AE1 SLC4 transporters: structure-function considerations.

A transport protein's turnover rate (TOR) is the maximum rate of substrate translocation under saturating conditions. This parameter represents the number of transporting events per transporter molecule (assuming a single transport site) per second (s). From this standpoint, a transporter's TOR is similar to an enzyme's catalytic constant. Knowledge of a transporter's TOR allows comparison of the transport capacity of various transporters at the molecular level as well as the total transport per cell and whole organ levels. Despite this, there is currently a very limited number of transporters, for which TOR has been determined experimentally. In the SLC4 transporter family of CO3 2-/HCO3 - transporters, erythrocyte AE1 (eAE1; SLC4A1) is the only member, for which TOR has been determined (∼50,000 s-1). Whether other SLC4 family members have similar TOR values is currently unknown. Here we report TOR measurements of the electrogenic Na+-CO3 2- cotransporter NBCe1-A (SLC4A4) and the kidney specific AE1 splice variant, kAE1, that play important roles in renal bicarbonate absorption and are mutated in proximal and distal renal tubular acidosis respectively. We have also remeasured the eAE1 TOR value for comparison. NBCe1-A had a TOR value of ∼30,400 s-1 whereas kAE1 and eAE1 had significantly higher values (62,000 s-1 and 60,500 s-1 respectively). We modeled the inward-facing (IF) conformation of NBCe1-A to determine conformational changes during its transport cycle. Comparison of this IF model with our previously determined cryoelectron microscopy (cryoEM) outward-facing (OF) conformation structure, demonstrates that NBCe1-A has an elevator-type transport mechanism with a small vertical ∼5 Å shift of the ion coordination site as we have previously shown for AE1. We speculate that this very small vertical movement plays an important role in contributing to the very high TOR numbers of SLC4 transporters.

Accurate Enthalpies of Formation for Bioactive Compounds from High-Level Ab Initio Calculations with Detailed Conformational Treatment: A Case of Cannabinoids.

Our recently developed approach based on the local coupled-cluster with single, double, and perturbative triple excitation [LCCSD(T)] model gives very efficient means to compute the ideal-gas enthalpies of formation. The expanded uncertainty (95% confidence) of the method is about 3 kJ·mol-1 for medium-sized compounds, comparable to typical experimental measurements. Larger compounds of interest often exhibit many conformations that can significantly differ in intramolecular interactions. Although the present capabilities allow processing even a few hundred distinct conformer structures for a given compound, many systems of interest exhibit numbers well in excess of 1000. In this study, we investigate how to reduce the number of expensive LCCSD(T) calculations for large conformer ensembles while controlling the error of the approximation. The best strategy found was to correct the results of the lower-level, surrogate model (density functional theory, DFT) in a systematic manner. It was also found that the error in the conformational contribution introduced by a surrogate model is mainly driven by a systematic (bias) rather than a random component of the DFT energy deviation from the LCCSD(T) target. This distinction is usually overlooked in DFT benchmarking studies. As a result of this work, the enthalpies of formation for 20 cannabinoid and cannabinoid-related compounds were obtained. Comprehensive uncertainty analysis suggests that the expanded uncertainties of the obtained values are below 4 kJ·mol-1.

Characterization of Hemoglobin Variants by Capillary Electrophoresis, UV-Vis, and FTIR Spectroscopy.

Hemoglobinopathies, hereditary disorders affecting the structure or production of hemoglobin, were detected by routine HbA1c measurements by capillary electrophoresis (CE) at the University Hospital Motol, Prague. The potential of ultraviolet-visible (UV-Vis) and Fourier-transform infrared (FTIR) spectroscopy for the detection and characterization of hemoglobinopathies was investigated. FTIR spectra were recorded with a very high resolution (0.5cm-1) with 128 scans. The broad amide I peak, located at 1700-1600cm-1, can be formed by superimposition of the conformational structures of hemoglobin. These secondary protein structures were subjected to mathematical analysis. The application of band narrowing techniques, followed by curve fitting and integration processes, provided the basis for the quantitative estimation of protein secondary structure. As a result, unambiguous differences in UV-Vis spectra among patients with presumably normal hemoglobin, an HbC or a hemoglobin S/hemoglobin G (HbS/HbG)-Philadelphia variant could not be demonstrated. However, FTIR spectra indicated slight differences in α-helix, β-turns, β-sheet, or random coil secondary hemoglobin structures for these mutations. In the spectral wavenumber range of 950-850cm-1, there were some obvious FTIR differences at specific wavenumbers between patients with normal hemoglobin and those with the HbC variant. Further investigations are needed with a sufficient number of hemoglobin variants to elucidate the potency of FTIR spectroscopy for the characterization of hemoglobinopathies.

Synthesis, Structure and Biological Activity of 2-Methyl-5-nitro-6-phenylnicotinohydrazide-Based Hydrazones.

The synthetic availability and wide range of biological activity of hydrazides and hydrazones make them attractive subjects for investigation. In this study, we focused on synthesis of 2-methyl-5-nitro-6-phenylnicotinohydrazide-based hydrazones derived from the corresponding substituted aldehydes. The structure of the obtained compounds was studied using NMR spectroscopy and DFT calculations. After repeated recrystallization, all the synthesized compounds remained as mixtures of isomers. As a result of a detailed analysis, we found that the duplication and bifurcation of signals in the 1H NMR spectra for some atoms is a consequence of the existence of four isomers, namely Z-I, Z-II, E-I and E-II. Duplicate proton signals with a chemical shift difference of 0.1-0.2 ppm and in a ratio of about 2:1 were noticed in the experimental data. By modeling the structures of individual configurations and conformations, Gibbs free energy values were obtained, which allowed us to estimate the approximate content of rotamers for the E-isomer equal to 3:2, which coincided with experimental data. We also tested the antibacterial and antifungal activity of the synthesized compounds.

Conformational Selectivity and Chiral Self-Assembly Structures of Crown Ethers on Metal Surfaces.

Crown ethers (CEs), macrocyclic polyethers, have attracted significant attention in supramolecular chemistry. It is known that they have many isomers due to their flexibility. It is challenging to select some exact conformation and tune the following self-assembly structure of CEs, and it has rarely been reported to date. Herein, by choosing 18-crown-6-ether and dibenzo-18-crown-6-ether for study, we report an effective stereoisomeric selectivity of CEs by a strategy of both chemical modification and CEs hosting Na/K ions. The conformational difference in CEs can further tune the molecular interactions, resulting in the chiral self-assembly structures of CEs. By the combination of scanning tunneling microscopy, density functional theory, and X-ray photoelectron spectroscopy, this study reveals the underlying mechanism of CEs in both conformational selectivity and the formation of chiral assembly structures.

Fine-tuning the molecular conformation and packing structures of coumarin-based luminogens to achieve distinct piezochromic properties upon mechanical grinding and under hydrostatic pressures.

Organic luminogens (OLs) exhibiting piezochromic (PC) properties have drawn much attention owing to their great application potentials. Both mechanical grinding (MG) and hydrostatic pressures (HP) can induce PC behaviors of OLs, and it is highly desirable to combine the two strategies to study the PC properties of OLs for comprehensively exploring their application scopes and deeply understanding the intrinsic PC mechanisms. In this work, four coumarin derivatives with different substituents at 3- or 4-positions are designed and synthesized to investigate their PC properties by MG and under HP. By MG, two materials show PL shifts, and the PL of the other two molecules barely change. In contrast, under HP, these molecules all exhibit PL shifts, but with different pressure coefficients. In addition, they show different reversibility of PL change after releasing HP. The different molecular conformation and packing structure changing manners of the materials, indicated by single-crystal and powder X-ray diffraction patterns, and in situ PL lifetime analysis, are anticipated to induce distinct PC behaviors upon disparate force stimulus. Our study indicates that fine-tuning the functionalization position of coumarin derivatives is a powerful strategy to engineer their molecular conformation and packing structures, thus developing versatile pressure-responsive OLs.

Interaction of starch nanoparticles with digestive enzymes and its effect on the release of polyphenols in simulated gastrointestinal fluids.

This study investigates the interaction of amino-modified starch nanoparticles (NH2-SNPs) and unmodified SNPs with pepsin and trypsin and the influence of the formation of protein coronas on the release of polyphenols. We discovered that NH2-SNPs bound loosely to pepsin, while they bound tightly to trypsin, by quartz crystal microbalance with dissipation monitoring and zeta potential measurement. SNPs did not easily bind to the two digestive enzymes. In addition, the influence of NH2-SNPs on digestive enzymes was investigated by ultraviolet-visible spectrophotometry, and circular dichroism spectroscopy, showing that the addition of NH2-SNPs had no effect on the conformational structure of pepsin and trypsin. Using NH2-SNPs and SNPs to load four polyphenols revealed that the nanoparticles had a slow-release effect on the polyphenols, but the presence of protein coronas had little effect on the release. The release was mainly related to the destruction of the starch-based carrier by the amylase in digestive enzymes.

Reconfigurable spin-decoupled conformal metasurface: 3D-printing with independent beam shaping and multi-focusing dual-channel reconfigurability techniques

This paper describes a 3D-printed conformal reconfigurable spin-decoupled metasurface and supports both independent beam shaping and dual-channel reconfigurability. The increasing complexity of metasurface structures and reconfigurable spin-decoupling among conformal structures are rarely reported due to their challenging properties. In this paper, a reconfigurable metasurface based on 3D-printing technology is proposed for reconfigurable spin-decoupled curved structures at 13.5–14.5 GHz. Curved surface spin-decoupling is realized for the first time and verified by simulation and experiment. Beam deflection (20° and 35°) and near-field focusing (100 mm and 150 mm) were achieved at different circularly polarized wave incidences. Switching the beam between the two states was achieved by incorporating the water-based metasurface. As a proof of concept, metasurfaces that have anomalous reflections in both channels were fabricated and measured. Furthermore, reconfigurable spin-decoupling was achieved using a water-based metasurface. This work extends the phase engineering approach in metasurfaces and may have a wide range of applications in communications, sensing, imaging, and camouflage.

Determining structures of RNA conformers using AFM and deep neural networks.

Much of the human genome is transcribed into RNAs1, many of which contain structural elements that are important for their function. Such RNA molecules-including those that are structured and well-folded2-are conformationally heterogeneous and flexible, which is a prerequisite for function3,4, but this limits the applicability of methods such as NMR, crystallography and cryo-electron microscopy for structure elucidation. Moreover, owing to the lack of a large RNA structure database, and no clear correlation between sequence and structure, approaches such as AlphaFold5 for protein structure prediction do not apply to RNA. Therefore, determining the structures of heterogeneous RNAs remains an unmet challenge. Here we report holistic RNA structure determination method using atomic force microscopy, unsupervised machine learning and deep neural networks (HORNET), a novel method for determining three-dimensional topological structures of RNA using atomic force microscopy images of individual molecules in solution. Owing to the high signal-to-noise ratio of atomic force microscopy, this method is ideal for capturing structures of large RNA molecules in distinct conformations. In addition to six benchmark cases, we demonstrate the utility of HORNET by determining multiple heterogeneous structures of RNase P RNA and the HIV-1 Rev response element (RRE) RNA. Thus, our method addresses one of the major challenges in determining heterogeneous structures of large and flexible RNA molecules, and contributes to the fundamental understanding of RNA structural biology.

Octaethyl vs Tetrabenzo Functionalized Ru Porphyrins on Ag(111): Molecular Conformation, Self-Assembly and Electronic Structure.

Metalloporphyrins on interfaces offer a rich playground for functional materials and hence have been subjected to intense scrutiny over the past decades. As the same porphyrin macrocycle on the same surface may exhibit vastly different physicochemical properties depending on the metal center and its substituents, it is vital to have a thorough structural and chemical characterization of such systems. Here, we explore the distinctions arising from coverage and macrocycle substituents on the closely related ruthenium octaethyl porphyrin and ruthenium tetrabenzo porphyrin on Ag(111). Our investigation employs a multitechnique approach in ultrahigh vacuum, combining scanning tunneling microscopy, low-energy electron diffraction, photoelectron spectroscopy, normal incidence X-ray standing wave, and near-edge X-ray absorption fine structure, supported by density functional theory. This methodology allows for a thorough examination of the nuanced differences in the self-assembly, substrate modification, molecular conformation and adsorption height.

Conformational changes in DNAand protein biomolecules in the pathogenesis of ischemic stroke

The study assessed conformational changes in DNA and protein biomolecules during ischemic stroke (IS) of varying severity using RAMAN spectroscopy. In patients with IS, the conformational structure of hemoporphyrin changes and, as a consequence, the ratio (I1355/I1550)/(I1375/I1580) (the affinity of hemoglobin for ligands) increases and an increase in I1375/I1172 (change in the conformation of pyrroles) is recorded. Changes in the spectra of genomic DNA are also observed at frequencies caused by stretching vibrations of primary amines (3400 cm–1), secondary amines and hydroxyls involved in hydrogen bonding (3100 cm–1), CH2 groups of sugar phosphates (2900 cm–1) , vibrations of vibrational bonds between nitrogenous bases and sugars (1400 cm–1). During IS, significant changes are observed in the spectra of genomic DNA and hemoglobin, which indicate conformational rearrangements of these molecules. In severe IS, the severity of the detected changes in the spectra of DNA and hemoglobin was maximum.

Continuously superior-strong carbon nanofibers by additive nanostructuring and carbonization of polyacrylonitrile jetting

Carbon nanofibers show the advantages of scale effects on electrical and mechanical properties for applications such as aerospace1,2, automotive3,4, and energy5,6, but have to confront the challenge of maximizing the role of scale effects. Here, a method of additive nanostructuring and carbonization of polyacrylonitrile (PAN) jetting for the nano-forming of carbon fibers is developed by understanding the electrostatic submicro-initiation of a PAN jetting, altering the microstructure of PAN-based jetting fibers at the nanoscale and implementing subsequent carbonization of PAN jetting nanofiber. Using this method of additive nanostructuring and carbonization in combination with the radial distribution pattern of shear stress, we find that the conformation of some molecular chains inside the PAN nanofibers is transformed into the zigzag conformation. The ability to materialize and carbonize such PAN nanofibers with various conformational structures in the form of arrays on diverse micro-structures and macro-substrates enables the forming of continuous carbon nanofibers with a diameter of ~20 nm and allows the tensile strength of carbon fibers to be enhanced to 212 GPa through the combination of zigzag conformation and nanoscale effects. These advantages create opportunities for the application of maximizing nanoscale effects that have not previously been technically possible.

DFT investigations on the influence of stacking on the electronic structure, absorption, and non-linear optical properties of 3,5-bis[4-(4-methylphenylcarbonyloxy)phenyl]-1,2,4-oxadiazole.

1,2,4-Oxadiazole serves as a fundamental building block driving advancements across diverse scientific and technological arenas, contributing to the creation of innovative materials for various applications including devices, sensors, medications, agrochemicals, and biomedical instruments. Employing density functional theory (DFT) methods, we investigate the impact of different conformers of an oxadiazole substituted derivative, specifically 3,5-bis[4-(4-methylphenylcarbonyloxy)phenyl]-1,2,4-oxadiazole, in both monomeric and stacked configurations (dimeric and tetrameric). We analyze the electronic structures of various conformers, including assessment of HOMO-LUMO energy gaps, to detect the influence of diverse substituents and stacking arrangements. We have also explored the stability of stacked structure in explicit solvent environment. Additionally, we examine absorption spectra, non-linear optical properties, and electronic circular dichroism to evaluate the potential applications of these molecules in optoelectronic devices. Our calculations showed that all the conformers were thermodynamically stable within an energy difference of 2.64kcalmol-1. The study also suggests possible application of the material in optical and electronic devices. DFT calculations were carried out using the CAM-B3LYP and wB97XD functionals with a 6-31 + G* all-electron basis set, paired with the SCRF/PCM solvation model, implemented in the Gaussian 09 package. Equilibrium structure was achieved by performing NPT and NVT simulations using the Gromacs package.

Chlorine Substitution Effect on the S1 Relaxation Dynamics of Chlorobenzene and Chlorophenols.

The S1 state relaxation dynamics of chlorobenzene (CB), 3-chlorophenol (3-CP), 3-CP·H2O, and 2-chlorophenol·H2O (2-CP·H2O) have been investigated by means of picosecond time-resolved pump-probe spectroscopy in a state-specific manner. For CB, the S1 state relaxes via the S1-S0 internal conversion in the low internal energy region (<2000 cm-1), whereas the direct C-Cl bond dissociation channel mediated by the upper-lying repulsive πσCCl* state is opened to give the rather sharp increase of the S1 relaxation rate in the high internal energy region (>2000 cm-1). A similar dynamic feature has been observed for 3-CP in terms of the lifetime behavior with an increase in the S1 internal energy, suggesting that the H atom tunneling dissociation reaction from OH might contribute less compared to the internal conversion, although it is not clear at the present time whether or not the sharp increase of the S1 relaxation rate in the high internal energy region of 3-CP (>1500 cm-1) is entirely due to that of the internal conversion. The fact that the internal conversion is facilitated by the Cl substitution implies that the energetic location of the S1/S0 conical intersection should have been strongly influenced by chlorine substitution on the aromatic ring. The approximate energetic location of the saddle point of the S1(ππ*)/πσCCl* conical intersection along the seam coordinate for CB or 3-CP could be inferred from the energy-dependent S1 lifetime measurements. It is discussed in comparison with the dynamic role of the S1(ππ*)/πσCCl* conical intersection, which is strongly influenced by the O-H···Cl intramolecular hydrogen bond in the rather complicated yet ultrafast S1 relaxation dynamics of the cis-2-CP. The S1 lifetimes of 3-CP·H2O and 2-CP·H2O reveal the importance of the conformational structures, especially in terms of the intramolecular hydrogen bonding.

Discovery of anti-SARS-CoV-2 S2 protein antibody CV804 with broad-spectrum reactivity with various beta coronaviruses and analysis of its pharmacological properties in vitro and in vivo.

The SARS-CoV-2 pandemic alerted the potential for significant harm due to future cross-species transmission of various animal coronaviruses to human. There is a significant need of antibody-based drugs to treat patients infected with previously unseen coronaviruses. In this study, we generated CV804, an antibody that binds to the S2 domain of SARS-CoV-2 spike protein, which is highly conserved across the coronavirus family and less susceptible to mutations. CV804 demonstrated broad cross-reactivities not only disease-associated human beta coronaviruses including SARS-CoV, MERS-CoV, HCoV-OC43, HCoV-HKU1 and with existing mutant strains of SARS-CoV-2 and but also with 20 representative animal-origin coronaviruses. CV804 exhibits strong antibody-dependent cellular cytotoxicity (ADCC) to SARS-CoV-2 spike protein expressed on cells in vitro, while completely lacks virus-neutralization activity. In animal models, CV804 suppressed disease progression caused by SARS-CoV-2 infection. Structural studies using HDX-MS combined with reactivity analysis with point mutants of recombinant spike proteins revealed that CV804 binds to a unique conformational epitope within the S2 domain of the spike proteins that is highly conserved among various coronaviruses. Overall, obtained data suggest that the non-neutralizing CV804 antibody recognizes the conformational structure of the spike protein displayed on the surface of infected cells and weakens the viral virulence by supporting the host immune cells' attack through ADCC activity in vivo. The CV804 epitope information revealed in this study is useful for designing pan-corona antibody therapeutics and universal coronavirus vaccines for preparing potential future pandemics.

Development of a New Salt of Piperine with Toluene Sulfonic Acid and Its Anti-Inflammation Effect In Vivo.

Piperine (PPN) is a natural compound with an anti-inflammation effect and low solubility. Hence, some molecular modifications have improved its solid-state character, including cocrystal formation. However, the salt structure has yet to be widely studied. In this research, PPN was reacted with toluene sulfonic acid (TSA), which was expected to increase its solubility and anti-inflammatory effects. This experiment used solid-state reactions and analysis, including thermal analysis, infrared spectroscopy, and powder X-ray diffractometry, to characterize the new multicomponent solid phase. Next, single crystal R-ray diffractometry was used to determine the final three-dimensional conformation structure. After that, the salt, which can be reproduced by wet grinding, was tested for improved stability and anti-inflammatory effects. As a result, the PPN-TSA multicomponent solid was confirmed as a solid salt with monoclinic packing, exhibiting better solubility and anti-inflammation effects. Thus, this new organic salt has the potential for further phytochemical compound development.