Supramolecular Organization Research Articles

Reshaping the aggregation landscape of benzothiadiazole employing steroidal scaffolds and conformationally free alkyne tethers

In this study, we target the introduction of conformational freedom to BTD, aiming to unlock new solid-state arrangements that were previously inaccessible, while striving to maintain its high fluorescence quantum yield. Our approach is grounded in a detailed exploration of the conformational space of designed molecules, employing molecular mechanics to predict and evaluate the impact of structural modifications on solubility and solid-state behavior. By strategically flanking the BTD core with steroidal fragments through alkyne bridges, we not only introduce bulky elements that disrupt the native crystal-packing landscape of pristine BTD, but also ensure significant rotational freedom around the carbon-carbon triple bonds. This design strategy allows the molecules to explore a wide range of conformations, potentially facilitating the formation of novel solid-state supramolecular arrangements.The synthesis of these compounds revealed that they exhibit adequate processability in solution and form solids that prove crystalline by powder X-ray diffraction, but do not readily form macroscopic crystals as BTD normally does. The steroid fragments play a crucial role in determining the supramolecular organization of these compounds. Depending on the specific functional groups present on the steroid skeleton, primary interactions such as hydrogen bonding and secondary interactions related to facial amphiphilicity dictate the overall arrangement of molecules in the solid state.Remarkably, the modifications successfully preserve the intrinsic high fluorescence quantum yield of the BTD core. This achievement underscores the potential of incorporating conformational flexibility into molecular design to access new material properties while retaining desirable photophysical characteristics.

Exploration of crystal structure, supramolecular organization, and computational studies of a novel pyrazole derivative: A structural and theoretical perspectives

An eminent challenge in contemporary medicine and pharmacy is the identification of powerful, biologically active, and benign anti-COVID drugs. The objective of this work is to synthesize 3-chloro-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxylic acid to investigate its properties using different spectroscopic methods. The crystal structure of the compound is determined using single-crystal X-ray diffraction methodology. Hirshfeld surface analysis was employed to evaluate the impact of intermolecular interactions on crystal packing. The interactions were visually depicted using 2D fingerprint plots, which highlighted the specific surface area associated with each interactant. Indications suggest that the crystal packing is mostly governed by C-H...O and N-H...O interactions, resulting in the formation of S(7) self-motif and R44(24) synthon, which greatly improve crystal stability. Density functional theory (DFT) was employed to better examine the structural and electrical characteristics. Computations were conducted at the 6–311+G(d,p) level to determine the optimal geometry, total energy, HOMO-LUMO gap, and vibrational spectra. The results showed a HOMO-LUMO gap of 3.092 eV, suggesting a moderate amount of stability. Bader et al. employed reduced density gradient (RDG) techniques and topological analysis, taking into account the quantum theory of atoms in molecules (QTAIM), to examine noncovalent interactions. Additionally, the molecule satisfies Lipinski's rule of five and exhibits encouraging pharmacokinetic activities. Additional in-silico investigations, including molecular docking, were conducted on the SARS-CoV-2 spike protein variation to assist in the advancement of enhanced vaccines and therapeutics.

Structure and noncovalent interaction analysis of half-sandwich chiral-at-metal organoruthenium complexes with planar and η6-arene-metal axial chirality

The preparation of organometallic compounds has provided new molecular complexity in molecular science. The stereochemistry of organometallics has long been a great challenge due to the large atom radius and more valency. Herein, eight ruthenium piano-stool shaped Ru complexes 2a-d and 3a-d with η6-planar chirality and Ru-center chirality were successfully synthesized and resolved, and the absolute configurations were determined by X-ray diffraction analysis. Racemization experiment revealed the stability differences of the Ru complexes in various solvents. Furthermore, in asymmetric unit of complex 3b, there are two conformers bearing opposite η6-arene-Ru axial chirality. In the supramolecular organization, all of the Ru complexes are stabilized by hydrogen bonding, C-H···π and Cl/I···π interactions. π···π interaction was only observed in complex 3b. The Hirshfeld surface analysis and 2D fingerprint plot show that the eight complexes have a similar contribution composed of different noncovalent interactions to the stabilization of crystal packing. Interestingly, only complex 3b has 3.5% C···C interaction. The pairwise interaction energies were calculated using CE-B3LYP energy model and further visualized by 3D-energy framework, which show that the dominant interaction for all complexes is dispersion. Theoretical energies of each conformer of complex 2a-d and 3a-d with η6-arene rotated at different angles was calculated by DFT method, and the energy barrier between the two conformations was around 2-3 kcal/mol. Halide ligand exchange experiments on complex (SRu)-1a were performed and the plausible mechanism was proposed. These results have provided new evidence for the design of molecules with specific fine stereochemical information for potential applications in medicinal and material chemistry.

Comparative analysis of polysaccharide and cell wall structure in Aspergillus nidulans and Aspergillus fumigatus by solid-state NMR

Invasive aspergillosis poses a significant threat to immunocompromised patients, leading to high mortality rates associated with these infections. Targeting the biosynthesis of cell wall carbohydrates is a promising strategy for antifungal drug development and will be advanced by a molecular-level understanding of the native structures of polysaccharides within their cellular context. Solid-state NMR spectroscopy has recently provided detailed insights into the cell wall organization of Aspergillus fumigatus, but genetic and biochemical evidence highlights species-specific differences among Aspergillus species. In this study, we employed a combination of 13C, 15N, and 1H-detection solid-state NMR, supplemented by Dynamic Nuclear Polarization (DNP), to compare the structural organization of cell wall polymers and their assembly in the cell walls of A. fumigatus and A. nidulans, both of which are key model organisms and human pathogens. The two species exhibited a similar rigid core architecture, consisting of chitin, α-glucan, and β-glucan, which contributed to comparable cell wall properties, including polymer dynamics, water retention, and supramolecular organization. However, differences were observed in the chitin, galactosaminogalactan, protein, and lipid content, as well as in the dynamics of galactomannan and the structure of the glucan matrix.

Tetrapyrrolic macrocycles self-organization into floating layers and sensory properties of their Langmuir-Schaefer films

The influence of the chemical structure of the 5,10,15,20-tetraphenylporphyrin (I) and 2-aza-21-carba-5,10,15,20-tetraphenylporphyrin (II) on their supramolecular organization in floating layers at the air/water interface and sensor properties in Langmuir-Schaefer films has been investigated. It was shown that a minor change in the macrocycle structure (namely, the replacement of a single nitrogen atom from the center to the periphery of macrocycle) has a considerable effect on the surface properties and hysteresis processes of the floating layers. Using the Bruster angle microscopy, it was established that both porphyrins aggregate even before the compression of their floating layers begins. The aggregation is more pronounced in porphyrin I. The analysis of hysteresis loops showed that the formation of a floating layer by the modified porphyrin II requires approximately 100 times more energy than for the unmodified porphyrin I. Using the Langmuir-Schaefer (LS) method, the floating layers were transferred onto solid substrates and the resulting thin films were analyzed by atomic force microscopy, scanning electron microscopy, polarization optical microscopy, and spectrophotometry. The combination of these methods revealed a general tendency of the porphyrins to form 3D structures on the surface of LS-films. The study of the basic properties of the porphyrin's LS-films showed that both porphyrins are diprotonated. The protonation process in porphyrin II occurs at a concentration of HClO4 that is 1000 times lower than that observed in porphyrin I. The greater tendency to protonation of porphyrin II is caused by the availability of both nitrogen atoms (the external nitrogen atom located at the macrocycle periphery and the internal nitrogen atom, which becomes more assesible to interactions due to the distortion of the macrocycle). As for the sensor properties of LS-films for iodide ion in aqueous solutions, it was observed that the diprotonated form of porphyrin I exhibited higher sensitivity due to a more developed film surface because of the presence of a greater number of 3D aggregates. The data obtained can be used in the development of efficient pH-controlled thin-film sensor materials for halide ions.

Crystal Structure, Supramolecular Organization, Hirshfeld Analysis, Interaction Energy, and Spectroscopy of Two Tris(4-aminophenyl)amine-Based Derivatives

The use of tris(4-aminophenyl)amine (TAPA) as central to the synthesis of both polyimines and polyimides and covalent organic frameworks and inorganic cages, among others, has grown in the last few years. The resulting materials exhibit high performance in their area of application. In this contribution, the crystal structures of two TAPA derivatives, triethyl (nitrilotris(benzene-4,1-diyl))tricarbamate (1) and triethyl 2,2′,2″-((nitrilotris(benzene-4,1-diyl))tris(azanediyl))tris(2-oxoacetate) (2), are described. The molecular and supramolecular structures of both compounds were compared between them and with analogous compounds. The analyses of their vibrational and 13C-CPMAS NMR spectroscopies, as well as their thermal stability, were included and corelated with the crystal structure. Hirshfeld surface analysis on the crystal structures of both TAPA derivatives revealed the stabilization of the crystal network via the amide N—H∙∙∙O interactions of dispersive nature in the carbamate, whereas dispersive carbonyl–carbonyl interactions also played a competitive role in the supramolecular arrangement of the oxamate. Interaction energy DFT calculations performed at the B3LYP/6-31G(d,p) level allowed us to estimate the energy contributions and nature of several interactions in terms of the stability of both crystal lattices.

Membrane transport of rare earth metal ions N, N’-bisdioctylphosphorylmethyl-1,4-diaminobutane by the active transport mechanism

The method of membrane extraction for rare earth elements (REE) using the carrier N, N’-bisdioctylphosphorylmethyl-1,4-diaminobutane (DPDA-8) ions, leveraging an active transport mechanism, has been optimized. The distribution of DPDA-8 within the membrane pores was confirmed using scanning electron microscopy (SEM). Both light and heavy REE extractions from a simulated solution using DPDA-8 and trioctylphosphine oxide (TOPO) in 1,2-dichlorobenzene were explored. The influence of feed solution pH, carrier and anion concentration, supported liquid membrane (SLM) type and stability, and cell temperature, among other parameters, were meticulously examined. The results indicate a decrease in permeability with a decrease in feed solution pH attributed to competitive acid transport through the membrane. Additionally, the formation of H-complexes between carriers and perchloric or phosphoric acids was investigated using Fourier Transform Infrared (FTIR) spectroscopy and X-ray diffraction (XRD) techniques. Changes in the stretching bands of amino and phosphine oxide groups in DPDA-8 were monitored and characterized. XRD analysis of the crystal structures of salts DPDA-6·ClO4 and DPDA-12·H2PO4 revealed a two-dimensional layered supramolecular organization with varying anion positions relative to hydrophobic fragments. The DPDA-8 carrier demonstrated significantly higher permeability values compared to TOPO, with differences in permeability exceeding twofold for certain metals. FTIR spectroscopy identified the main coordination centers of DPDA-8 during the liquid–liquid extraction of specific REEs.

Supramolecular structure of epoxy oligomers

AbstractBased on the generalized results of experimental methods for studying the viscosity of oligomers—DSC, electron microscopy, NMR spin echo, x‐ray diffraction analysis, edge wetting angles, laser microinterference, atomic force microscopy, dynamic light scattering, plastic flow—an analysis of the features of the supramolecular organization of melts and solutions of epoxy oligomers was carried out. In terms of thermofluctuation approach, a qualitative assessment of the structural elements forming a macroscopic polymer body is given, and direct morphological evidence of their structure, thermodynamic stability, size evolution with temperature changes and elastic‐strain effects is presented. A mathematical apparatus has been developed to describe the destruction of domains in solutions and melts of oligomers. Analytical equations have been proposed for calculating the time of thermofluctuation relaxation of domains. Based on the analysis of the supramolecular structure of dian epoxy oligomers by transmission electron microscopy and translational mobility of oligomer macromolecules in the high temperature region (Tg + 150°C), it has been suggested that a structure such as “flickering clusters” of free volume elements is formed in the oligomer melts.Highlights Phase diagrams of aromatic and aliphatic epoxy oligomers have been constructed. The influence of molecular weight on the activation energy of diffusion of viscous flow is estimated. It has been shown that the supramolecular structure of epoxy oligomers in the melt contains “flickering clusters.” The lifetime of density fluctuations of epoxy oligomers domains in melts has been calculated.

Designing Highly Ordered Helical and Nonhelical Porous Crystalline and Disordered Nonhelical Columnar Liquid Crystalline Self-Organizations.

Helical self-organizations are equilibrium structures responsible for the assembly of nonequilibrium and equilibrium living and synthetic systems. Racemic helical columnar systems transform into one-handed systems with the help of enantiomerically rich or pure components. Racemic, enantiomerically rich, and enantiomerically pure helical periodic arrays of columns are analyzed by oriented fiber X-ray diffraction (XRD). With few exceptions, highly ordered helical 3-D organizations as generated from homochiral columns cannot be obtained from achiral, racemic, or enantiomerically rich helical columns. Here, we report an unprecedented class of nonhelical porous ordered, disordered nonhelical columnar liquid crystalline (LC) self-organizations and columnar liquids constructed from AB4 to AB9 isomeric terphenyls by molecular design unwinding of a 3-D helical organization. A library of 16 nonhelical porous ordered, disordered columnar and four liquids was designed by employing as a model a closely related achiral AB4 meta-terphenyl, which self-organizes one of the most perfect synthetic ordered columnar hexagonal helices known. A general molecular mechanism to unwind highly ordered 3-D helices into nonhelical porous columnar ordered LCs and liquids was elaborated to design this transformation, which provided unprecedented nonequilibrium synthetic systems. This methodology is expected to be general for transformation of helical macromolecular and supramolecular organizations into nonhelical crystals, LCs, and liquids.

Comparative Analysis of Polysaccharide and Cell Wall Structure in Aspergillus nidulans and Aspergillus fumigatus by Solid-State NMR.

Invasive aspergillosis poses a significant threat to immunocompromised patients, leading to high mortality rates associated with these infections. Targeting the biosynthesis of cell wall carbohydrates is a promising strategy for antifungal drug development and will be advanced by a molecular-level understanding of the native structures of polysaccharides within their cellular context. Solid-state NMR spectroscopy has recently provided detailed insights into the cell wall organization of Aspergillus fumigatus, but genetic and biochemical evidence highlights species-specific differences among Aspergillus species. In this study, we employed a combination of 13C, 15N, and 1H-detection solid-state NMR, supplemented by Dynamic Nuclear Polarization (DNP), to compare the structural organization of cell wall polymers and their assembly in the cell walls of A. fumigatus and A. nidulans, both of which are key model organisms and human pathogens. The two species exhibited a similar rigid core architecture, consisting of chitin, α-glucan, and β-glucan, which contributed to comparable cell wall properties, including polymer dynamics, water retention, and supramolecular organization. However, differences were observed in the chitin, galactosaminogalactan, protein, and lipid content, as well as in the dynamics of galactomannan and the structure of the glucan matrix.

Influence of chitosanon on the ability of LPS to interact with cells of the immune system

Complexes of lipopolysaccharide (LPS) from the bacterium Escherichia coli and chitosan (CN) with a molecular weight of 5 kDa were obtained and their supramolecular organization was studied. Using atomic force microscopy, it was shown that during the formation of complexes there is a transition from the micellar structure of the original LPS to linear network structures uniformly distributed over the surface of mica. The stability of LPS-CN complexes of various stoichiometries in biological media in the presence of serum proteins was investigated. It was shown that complexes with an LPS:CN ratio of 1:1 in the presence of serum proteins lost their surface charge and tended to aggregate; while complexes with maximum saturation of CN (1:5) did not aggregate under these conditions and maintained their surface charge. The effect of CNs of different molecular weights on the ability of LPS to interact with neutrophils in human whole blood was studied. It was observed that LPS-CN complexes were capable of binding to neutrophils and entering the cell, and this ability was enhanced in the presence of serum proteins. Chitosan exhibited the ability to suppress the synthesis of the proinflammatory cytokine TNF-α, induced by LPS, not only as part of the complex but also when cells were pretreated with a polycation.

Electron microscopy of stable electrophoretic fractions of natural humic acids – the key to the understanding of their structural organization

Transmission electron microscopy (TEM) with contrast staining by uranyl acetate solution was used to study morphological differences between soil humic acids (HAs) and their A, B and C + D fractions obtained using coupling preparative low-pressure size exclusion chromatography and analytical polyacrylamide gel electrophoresis. The electrophoretic mobility of fractions varied in order C + D B A. The distribution of various morphological elements between fractions showed that large structures such as vesicle-like formations 70–150 nm long and 30–80 nm wide with clear edges were found exclusively in fraction A and occupied ~55% of the TEM image area. On the other hand, long fibrils with a length of 60–100 nm, a width of 4–6 nm and a thickness of 2–3 nm, as well as their bundles with a length of 150 nm and a diameter of 30–70 nm were identified only in the C + D fraction and occupied ~59 % area of TEM images. Smaller morphological elements such as point particles with a diameter of 2–3 nm, ring particles with a diameter of 4–6 nm, worm-shaped short particles with a length of 20–30 nm, and spheroids with a diameter of 10– 30 nm were observed in all samples, but in varying quantities. Significant morphological differences between the fractions can be explained by their composition, previously established by using a few physico-chemical methods. The ratio Car(165–108 ppm)/Calk(108–0 ppm), or aromaticity index, calculated from 13C-NMR, could be one of the indicators of the various morphological structures formation. The obtained TEM results clearly confirm the supramolecular organization of soil HAs.

Facile preparation and study of supramolecular architecture of an efficient nanocomposite LB film AHSM/SA based on azo-functionalized hockey stick-shaped mesogen at air-water and air-solid interface

Hockey stick-shaped mesogens are fascinating thermotropic liquid crystal systems owing to their exceptional supramolecular assembly properties and shape anisotropy compared to conventional rod-and bent-shaped mesogens. In this article, we present an investigation of the supramolecular organization of a new azo-functionalized hockey stick-shaped mesogen with stearic acid at the air-water interface and air-solid interfaces by applying the Langmuir-Blodgett film deposition method. The incorporation of stearic acid can change the molecular organization of azo-functionalized hockey stick-shaped mesogen at an aqueous interface through hydrophobic-hydrophobic interactions and form a supramolecular nanostructure at the solid interface. The interfacial nature of the Langmuir monolayer was studied by recording the isotherm (surface pressure area, π–A), which was further analyzed by using Brewster angle microscopy. The significant reduction in molecular area, increased surface pressure, and lower isotherm slope of the AHSM/SA composite mixture indicate the hybrid AHSM/SA monolayer's greater stability compared to pure AHSM. BAM images of the AHSM/SA composite signify nanostructure aggregates formed by the interaction of AHSM and SA molecules at the air-water interface. Field emission scanning electron microscopic analysis of composite films revealed the formation of supramolecular domains. The impact of changing the surface pressure and the number of depositions on the morphology of the composite film surface was monitored using field emission scanning electron microscopy. The supramolecular H-type aggregation of azo-functionalized hockey stick-shaped mesogen and stearic acid molecules in the composite LB film was characterized using UV–visible absorption and steady-state fluorescence spectroscopy. The adsorption of stearic acid onto azo-functionalized hockey stick-shaped mesogen via hydrophobic interactions was confirmed by Fourier transform infrared spectroscopy of the composite Langmuir Blodgett film. Further, Raman spectroscopy of the LB films of the AHSM/SA composites is distinct from the pristine film components due to the merging of signals at similar wave numbers for both SA and AHSM with a lack of typical packing pattern further supported by PXRD studies of the films.

Study on the induced polymeric protein aggregation and immunoreactivity in biscuits enriched with peanut flour

This work deals with the study on the protein extractability of biscuits incurring different percentages of roasted peanut flour. The presence of two different flours influenced the rate of protein aggregation and protein extractability, according to the percentage of roasted peanut flour added to the formulation and assessing these features by testing the use of two buffers. Results showed that gluten network arrangement of biscuits was influenced by the flours mixture besides the baking, with possible different protein organizations. Protein extractability was affected, underlining a higher content of protein aggregates at high molecular weight especially with the addition of 20% of peanut flour, characterized by hydrophobic and reducible covalent bonds, as suggested by the higher extractability obtained with the buffer with chaotropic and reducing agents.These results suggested a possible induced supramolecular protein organization in these products, which could affect the immunoreactivity of the main allergens occurred in the formulation.

Chiral Nanostructured Glycerohydrogel Sol-Gel Plates of Chitosan L- and D-Aspartate: Supramolecular Ordering and Optical Properties.

A comprehensive study was performed on the supramolecular ordering and optical properties of thin nanostructured glycerohydrogel sol-gel plates based on chitosan L- and D-aspartate and their individual components in the X-ray, UV, visible, and IR ranges. Our comparative analysis of chiroptical characteristics, optical collimated transmittance, the average cosine of the scattering angle, microrelief and surface asymmetry, and the level of structuring shows a significant influence of the wavelength range of electromagnetic radiation and the enantiomeric form of aspartic acid on the functional characteristics of the sol-gel materials. At the macrolevel of the supramolecular organization, a complex topography of the surface layer and a dense amorphous-crystalline ordering of polymeric substances were revealed, while at the nanolevel, there were two forms of voluminous scattering domains: nanospheres with diameters of 60-120 nm (L-) and 45-55 nm (D-), anisometric particles of lengths within ~100-160 (L-) and ~85-125 nm (D-), and widths within ~10-20 (L-) and ~20-30 nm (D-). The effect of optical clearing on glass coated with a thin layer of chitosan L-(D-)aspartate in the near-UV region was discovered (observed for the first time for chitosan-based materials). The resulting nanocomposite shape-stable glycerohydrogels seem promising for sensorics and photonics.

Columnar Mesomorphism in a Methylthio-Decorated Triindole for Enhanced Charge Transport.

We report a semiconducting triindole-based discotic liquid crystal (TRISMe) functionalized with six p-methylthiophenyl groups at its periphery. While initially a crystalline solid at room temperature, TRISMe transitions to a columnar hexagonal mesophase upon heating and retains this supramolecular organization upon subsequent cooling, despite having only three flexible alkyl chains attached to the core's nitrogens. The incorporation of methylthio groups effectively hinders tight molecular packing, stabilizing the columnar arrangement of this disk-shaped molecule. Single crystal analysis confirmed the high tendency of this compound to organize into a columnar architecture and the role played by the methylthio groups in reinforcing such structure. The mesomorphic behavior of TRISMe provides an opportunity for processing from its molten state. Notably, our research reveals significant differences in charge transport depending on the processing method, whether solution drop-casting or melt-based. TRISMe shows hole mobility values averaging 3 × 10-1 cm2 V-1 s-1 when incorporated in diode-type devices from the isotropic melt and annealed at the mesophase temperature, estimated by SCLC (space-charge-limited current) measurements. However, when integrated into solution-processed organic field-effect transistors (OFETs), crystalline TRISMe exhibits a hole mobility of 3 × 10-4 cm2 V-1 s-1. The observed differences can be attributed to a beneficial supramolecular assembly achieved in the mesophase in spite of its lower order. These results emphasize the material's potential for applications in easy-to-process electronic devices and highlight the potential of methylthio moieties in promoting columnar mesophases.

Structure and distinct supramolecular organization of a PSII-ACPII dimer from a cryptophyte alga Chroomonas placoidea

Cryptophyte algae are an evolutionarily distinct and ecologically important group of photosynthetic unicellular eukaryotes. Photosystem II (PSII) of cryptophyte algae associates with alloxanthin chlorophyll a/c-binding proteins (ACPs) to act as the peripheral light-harvesting system, whose supramolecular organization is unknown. Here, we purify the PSII-ACPII supercomplex from a cryptophyte alga Chroomonas placoidea (C. placoidea), and analyze its structure at a resolution of 2.47 Å using cryo-electron microscopy. This structure reveals a dimeric organization of PSII-ACPII containing two PSII core monomers flanked by six symmetrically arranged ACPII subunits. The PSII core is conserved whereas the organization of ACPII subunits exhibits a distinct pattern, different from those observed so far in PSII of other algae and higher plants. Furthermore, we find a Chl a-binding antenna subunit, CCPII-S, which mediates interaction of ACPII with the PSII core. These results provide a structural basis for the assembly of antennas within the supercomplex and possible excitation energy transfer pathways in cryptophyte algal PSII, shedding light on the diversity of supramolecular organization of photosynthetic machinery.

Protein Ingredient Quality within Infant Formulas Impacts Plasma Amino Acid Concentrations in Neonatal Minipiglets

BackgroundInfant formulas (IFs), the only adequate substitute to human milk, are complex matrices that require numerous ingredients and processing steps that may impact protein digestion and subsequent amino acid (AA) absorption. ObjectivesThe objective was to understand the impact of the protein ingredient quality within IFs on postprandial plasma AA profiles. MethodsFour isonitrogenous and isocaloric IFs were produced at a semi-industrial scale using whey proteins from different origins (cheese compared with ideal whey) and denaturation levels (IF-A, -B, -C), and caseins with different supramolecular organizations (IF-C, -D). Ten Yucatan minipiglets (12- to 27-d-old) were used as a human infant model and received each IF for 3 d according to a Williams Latin square followed by a 2-d wash-out period. Jugular plasma was regularly sampled from 10 min preprandial to 4 h postprandial on the third day to measure free AAs, urea, insulin, and glucose concentrations. Data were statistically analyzed using a mixed linear model with diet (IFs), time, and sex as fixed factors and piglet as random factor. ResultsIFs made with cheese whey (IF-A and -B) elicited significantly higher plasma total and essential AA concentrations than IFs made with ideal whey (IF-C and -D), regardless of the pre- and postprandial times. Most of the differences observed postprandially were explained by AA homeostasis modifications. IFs based on cheese whey induced an increased plasma concentration of Thr due to both a higher Thr content in these IFs and a Thr-limiting degrading capability in piglets. The use of a nonmicellar casein ingredient led to reduced plasma content of AA catabolism markers (IF-D compared with IF-C). ConclusionsOverall, our results highlight the importance of the protein ingredient quality (composition and structure) within IFs on neonatal plasma AA profiles, which may further impact infant protein metabolism.

A comprehensive study on the intermolecular interactions and energy frameworks exist in crystal structures of Form-I, Form-II and Form-III polymorphs of Ethyl maltol

The present study serves as a comprehensive investigation into the molecular crystal structures of three polymorphic forms of ethyl maltol. Crystal structures of the polymorphs grown via slow evaporation and quench cooling crystallization processes were determined through single crystal X-ray diffraction (SCXRD) analysis. Through the utilization of SCXRD data CIF file as an input, we explored the nature and strength of intermolecular interactions, atom pair close contacts, interaction types, 2D fingerprint plots, surface characteristics and percentage of voids present within each polymorph of ethyl maltol. The comparative analysis involves the application of advanced methods, such as Hirshfeld surface analysis and 3D-energy frameworks using Crystal Explorer 17.5. In a supramolecular organization, intermolecular interaction between the carbonyl and hydroxyl groups is a collective structural motif employed among the three polymorphs. However the three polymorphs share common structural features, but the conformations within the crystal packing of each form are different from each other. Shape Index and Curvedness surfaces reveal π stacking interactions with varying properties on differing sides of the molecular moieties between the polymorph. Fingerprint analysis emphasizes that (H…H) is the predominant interaction whereas (O…H) and (H…O) interactions contribute more towards the generation of H-bond interactions in the structure of ethyl maltol polymorphs. The crystal structures of all the three ethyl maltol polymorphs stabilized by various intermolecular contacts within the Hirshfeld surface area was comparable. The interaction energy and the 3D-energy frameworks offer a visualization of the crystal packing topology, enhancing our understanding of the three-dimensional arrangement of molecules and their structural stability. The resulting overall average total energy values for Form-I, Form-II and Form-III polymorphs of ethyl maltol are -56.3 kJ /mol, -74 kJ /mol and -80.45 kJ /mol respectively which reveals that all the three polymorphs show a significant difference in their total energies and reveals further that Form-III polymorph of ethyl maltol is the most stable one while Form-I is the least stable and Form-II is metastable relatively. Moreover, the dispersion energy framework is predominant over the electrostatic energy framework. The void analysis reveals the percentage of volume occupied by the voids present in the unit cell of Form-I, Form-II, and Form-III polymorphs of ethyl maltol are found to be 7.20%, 6.55 %, and 9.43% respectively.

Pioglitazone Phases and Metabolic Effects in Nanoparticle-Treated Cells Analyzed via Rapid Visualization of FLIM Images.

Fluorescence lifetime imaging microscopy (FLIM) has proven to be a useful method for analyzing various aspects of material science and biology, like the supramolecular organization of (slightly) fluorescent compounds or the metabolic activity in non-labeled cells; in particular, FLIM phasor analysis (phasor-FLIM) has the potential for an intuitive representation of complex fluorescence decays and therefore of the analyzed properties. Here we present and make available tools to fully exploit this potential, in particular by coding via hue, saturation, and intensity the phasor positions and their weights both in the phasor plot and in the microscope image. We apply these tools to analyze FLIM data acquired via two-photon microscopy to visualize: (i) different phases of the drug pioglitazone (PGZ) in solutions and/or crystals, (ii) the position in the phasor plot of non-labelled poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs), and (iii) the effect of PGZ or PGZ-containing NPs on the metabolism of insulinoma (INS-1 E) model cells. PGZ is recognized for its efficacy in addressing insulin resistance and hyperglycemia in type 2 diabetes mellitus, and polymeric nanoparticles offer versatile platforms for drug delivery due to their biocompatibility and controlled release kinetics. This study lays the foundation for a better understanding via phasor-FLIM of the organization and effects of drugs, in particular, PGZ, within NPs, aiming at better control of encapsulation and pharmacokinetics, and potentially at novel anti-diabetics theragnostic nanotools.