Supramolecular Association Research Articles

Supramolecular associations between atypical oxidative phosphorylation complexes of Euglena gracilis

In vivo associations of respiratory complexes forming higher supramolecular structures are generally accepted nowadays. Supercomplexes (SC) built by complexes I, III and IV and the so-called respirasome (I/III2/IV) have been described in mitochondria from several model organisms (yeasts, mammals and green plants), but information is scarce in other lineages. Here we studied the supramolecular associations between the complexes I, III, IV and V from the secondary photosynthetic flagellate Euglena gracilis with an approach that involves the extraction with several mild detergents followed by native electrophoresis. Despite the presence of atypical subunit composition and additional structural domains described in Euglena complexes I, IV and V, canonical associations into III2/IV, III2/IV2 SCs and I/III2/IV respirasome were observed together with two oligomeric forms of the ATP synthase (V2 and V4). Among them, III2/IV SC could be observed by electron microscopy. The respirasome was further purified by two-step liquid chromatography and showed in-vitro oxygen consumption independent of the addition of external cytochrome c.

Metallo-Supramolecular Coordination Polymers Based on Amidopyridine Derivatives of Pillar[5]arene and Cu(II) and Pd(II) Cations: Synthesis and Recognition of Nitroaromatic Compounds.

Decasubstituted pillar[5]arenes containing amidopyridine fragments have been synthesized for the first time. As was shown by UV-vis spectroscopy, the pillar[5]arenes with p-amidopyridine fragments form supramolecular associates with Cu(II) and Pd(II) cations in methanol in a 2:1 ratio. Using a sol-gel approach these associates are transformed into metallo-supramolecular coordination polymers (supramolecular gels) which were characterized as amorphous powders by scanning electron microscopy (SEM) and dynamic light scattering (DLS). The powders are able to selectively adsorb up to 46% of nitrophenols from water and were incorporated into an electrochemical sensor to selectively recognize them in aqueous acidic solution.

Single-Point Hessian Calculations for Improved Vibrational Frequencies and Rigid-Rotor-Harmonic-Oscillator Thermodynamics.

The calculation of harmonic vibrational frequencies (HVF) to interpret infrared (IR) spectra and to convert molecular energies to free energies is one of the essential steps in computational chemistry. A prerequisite for accurate thermostatistics so far was to optimize the molecular input structures in order to avoid imaginary frequencies, which inevitably leads to changes in the geometry if different theoretical levels are applied for geometry optimization and frequency calculations. In this work, we propose a new method termed single-point Hessian (SPH) for the computation of HVF and thermodynamic contributions to the free energy within the modified rigid-rotor-harmonic-oscillator approximation for general nonequilibrium molecular geometries. The key ingredient is the application of a biasing potential given as Gaussian functions expressed with the root-mean-square-deviation (RMSD) in Cartesian space in order to retain the initial geometry. The theory derived herein is generally applicable to quantum mechanical (QM), semiempirical QM, and force-field (FF) methods. Besides a detailed description of the underlying theory including the important back-correction of the biased HVF, the SPH approach is tested for reaction paths, molecular dynamics snapshots of crambin, and supramolecular association free energies in comparison to high-level density functional theory (DFT) values. Furthermore, the effect on IR spectra is investigated for organic dimers and transition-metal complexes revealing improved spectra at low theoretical levels. On average, DFT reference free energies are better reproduced by the newly developed SPH scheme than by conventional calculations on freely optimized geometries or without any relaxation.

Formation and evolution of the nanoparticle environmental corona: The case of Au and humic acid

Studying the behaviour of nanomaterials after their release into natural water is essential to understand the risk associated to their environmental exposure. In particular, the interaction and adsorption of dissolved organic matter onto nanoparticles strongly influence the behaviour and fate of nanomaterials in natural water systems. We herein study the interaction of Au and Ag nanoparticles and humic acids, the principal component of natural dissolved organic matter. Physicochemical characterization results showed the formation of an organic matter corona, consisting of two layers: a “hard” one, firmly bound to the nanoparticle surface, and a “soft” one, in dynamic equilibrium and, consequently, highly dependent on the media organic matter concentration. The extent of the electro-steric stabilization of the so called environmental corona depends on the size of the supramolecular association of humic acid (which depends on its hydrophilic and lipophilic moieties), the nanoparticle size, the total concentration of organic matter in the media, and the ratio between them. Interestingly, environmental coronas can eventually prevent Ca2+ and Mg2+ induced aggregation at concentrations range present in most of the freshwater bodies. The humic coating formed on top of the Au or control Ag nanoparticles presented a similar profile, but the corrodibility of Ag led to a more natural detachment of the corona. These results were further confirmed by exposing the nanoparticles to a model of natural water and standard mud (LUFA 2.2 dispersion). In the latter case, after several days, nanoparticle sedimentation was observed, which was attributed to interactions with macro organic and inorganic matter (fraction larger than particulate matter).

Adamantane Functionalized Poly(2-oxazoline)s with Broadly Tunable LCST-Behavior by Molecular Recognition.

Smart or adaptive materials often utilize stimuli-responsive polymers, which undergo a phase transition in response to a given stimulus. So far, various stimuli have been used to enable the modulation of drug release profiles, cell-interactive behavior, and optical and mechanical properties. In this respect, molecular recognition is a powerful tool to fine-tune the stimuli-responsive behavior due to its high specificity. Within this contribution, a poly(2-oxazoline) copolymer bearing adamantane side chains was synthesized via triazabicyclodecene-catalyzed amidation of the ester side chains of a poly(2-ethyl-2-oxazoline-stat-2-methoxycarbonylpropyl-2-oxazoline) statistical copolymer. Subsequent complexation of the pendant adamantane groups with sub-stoichiometric amounts (0–1 equivalents) of hydroxypropyl β-cyclodextrin or β-cyclodextrin enabled accurate tuning of its lower critical solution temperature (LCST) over an exceptionally wide temperature range, spanning from 30 °C to 56 °C. Furthermore, the sharp thermal transitions display minimal hysteresis, suggesting a reversible phase transition of the complexed polymer chains (i.e., the β-cyclodextrin host collapses together with the polymers) and a minimal influence by the temperature on the supramolecular association. Analysis of the association constant of the polymer with hydroxypropyl β-cyclodextrin via 1H NMR spectroscopy suggests that the selection of the macrocyclic host and rational polymer design can have a profound influence on the observed thermal transitions.

Turning Rubber into a Glass: Mechanical Reinforcement by Microphase Separation.

Supramolecular associations provide a promising route to functional materials with properties such as self-healing, easy recyclability or extraordinary mechanical strength and toughness. The latter benefit especially from the transient character of the formed network, which enables dissipation of energy as well as regeneration of the internal structures. However, recent investigations revealed intrinsic limitations in the achievable mechanical enhancement. This manuscript presents studies of a set of telechelic polymers with hydrogen-bonding chain ends exhibiting an extraordinarily high, almost glass-like, rubbery plateau. This is ascribed to the segregation of the associative ends into clusters and formation of an interfacial layer surrounding these clusters. An approach adopted from the field of polymer nanocomposites provides a quantitative description of the data and reveals the strongly altered mechanical properties of the polymer in the interfacial layer. These results demonstrate how employing phase separating dynamic bonds can lead to the creation of high-performance materials.

Influence of molecular geometry on the formation, architecture and dynamics of H-bonded supramolecular associates in 1-phenyl alcohols

Combination of calorimetric, dielectric, infrared, diffraction studies and quantum DFT computations was used to analyze the impact of the molecular architecture of a set of four 1-phenyl alcohols (1-phenylethanol, 1-phenyl-1-propanol, 1-phenyl-1-butanol and 2-methyl-1-phenyl-1-propanol) on their glass transition temperature, molecular dynamics, relaxation processes, hydrogen-bonding pattern and intermolecular association. We showed that all these alcohols form H-bonded supramolecular nanoassociates even at room temperature, despite containing a steric hindrance in the form of the phenyl ring in the most disfavored position. However, the concentration and the size of the H-bonded structures as well as the mutual arrangement of molecules in these clusters are tremendously affected by the molecular architecture. In linear-shaped 1-phenyl alcohols, i.e., 1-phenylethanol, 1-phenyl-1-propanol, 1-phenyl-1-butanol, the intermolecular O-H···O bonds organize themselves into chain-like patterns. Moreover, these alcohols are characterized by similar strength of intermolecular H bonds at each temperature and similar glass transition temperature. In turn, the globular molecular shape of 2-methyl-1-phenyl-1-propanol leads to a weakening of H bonds in this system, an increase in the glass transition temperature and the formation of supramolecular clusters in which O-H···O connections imply ring-like organization of molecules. Finally, these studies clearly show that unlike the glass transition temperature, the molecular dynamics of the 1-phenyl alcohols in the liquid state is not only affected by the molecular architecture and hydrogen bond strength but also by the morphology of the associates composed of H-linked molecules.

Cyclodextrins: promising scaffolds for MRI contrast agents.

Magnetic resonance imaging (MRI) is a powerful tool for non-invasive, high-resolution three-dimensional medical imaging of anatomical structures such as organs and tissues. The use of contrast agents based on gadolinium chelates started in 1988 to improve the quality of the image, since researchers and industry focused their attention on the development of more efficient and stable structures. This review is about the state of the art of MRI contrast agents based on cyclodextrin scaffolds. Chemical engineering strategies are herein reported including host–guest inclusion complexation and covalent linkages. It also offers descriptions of the MRI properties and in vitro and in vivo biomedical applications of these emerging macrostructures. It highlights that these supramolecular associations can improve the image contrast, the sensitivity, and the efficiency of MRI diagnosis by targeting cancer tumors and other diseases with success proving the great potential of this natural macrocycle.

Different Detergent Stability of ATP Synthase from Pea, Winter Wheat and Maize Mitochondria

Mitochondrial ATP synthase is a macromolecular nanomachine, which produces most of the ATP in the cell. This enzyme is located in inner mitochondrial membrane in the form of dimers, which assemble into long rows at the cristae rims. Dimers of ATP synthase are sensitive to detergent treatment in many organisms, as a result of which they mainly dissociate into monomers. Plant enzyme is also very detergent-sensitive, nevertheless, it can be assumed that the detergent-sensitivity or, vice versa, detergent-stability of the enzyme under the treat-ment may vary in different plant species. In this regard, the aim of this work was to study the detergent-stability, as well as the activity of various forms of ATP synthase, solubilized from the mitochondria of different plant species. For this purpose, we used organelles isolated from etiolated pea, winter wheat, and maize shoots. These species belong to different families (Poaceae and Fabaceae), clades (monocots and dicots) and, in addition, differ in their low temperature tolerance. For the solubilization of organelles, a mild non-ionic detergent digitonin was used, which preserved and stabilized the supramolecular associations of membrane proteins. Using 1D BN-PAGE followed by ingel enzyme activity assay, it was shown that ATP synthase in all studied species was solubilized mainly as monomers Va and Vb, dimer Vb2, supercomplex IV1Va2, and minor subcomplex F1. In the course of the study, for the first time, differences in the detergent-stability of dimeric and monomeric forms of the enzyme between the studied species were revealed. It was found that the dimeric form in maize and the monomeric form in winter wheat were the most stable; while, pea ATP synthase had the highest activity. The relationship between the revealed features and the life strategy of the species is assumed and discussed.

Capturing the dynamic association between a tris-dipicolinate lanthanide complex and a decapeptide: a combined paramagnetic NMR and molecular dynamics exploration.

In the realm of biomolecules, peptides can present a large diversity of structures. Our study sheds new light on the structural interplay between a tris-dipicolinate lanthanide probe and a decapeptide SASYKTLPRG. Although a rather trivial, electrostatically driven interaction was expected, the combination of paramagnetic NMR and molecular dynamics simulations reveals a highly dynamic association process and allows for providing extensive insights into the interaction sites and their occupancy. This study highlights the importance of a large conformational sampling to reconcile characteristic time in NMR with molecular dynamics simulations, where sampling in the microsecond range is needed. This study opens the door for a detailed mechanistic elucidation of the early steps of lanthanide complex-peptide or lanthanide complex-protein interaction or self-assembly processes.

Supramolecular Association and Nanostructure Formation of Liquid Crystals and Polymers for New Functional Materials

AbstractWe here describe our various concepts and achievements for material science, which have been introduced through liquid-crystalline (LC) and polymer chemistry. They have resulted in the development of new classes of functional organic, polymer, and hybrid materials. Supramolecular LC complexes and polymers with well-defined structures were found to be built through complimentary hydrogen bonding between carboxylic acid and pyridine. Since then, a variety of intermolecular interactions such as hydrogen bonding, ionic interactions, ion-dipolar interactions, and halogen bonding were used for the formation of supramolecular liquid crystal organic materials and polymers. The nanosegregation in molecular assemblies in liquid crystals leads to the various 1D, 2D and 3D self-assembled nanostructures. These strategy and material designs lead to the development of new dynamically functional materials, which exhibit stimuli-responsive properties, photoluminescence, transport of charge, ions, and molecules, electro-optic properties, and templates. We also show new hybrid liquid crystals, biomineral-inspired nanorod and nanodisk liquid crystals. These nanomaterials form colloidal LC solutions, which exhibit stimuli-responsive properties.

STRUCTURAL-GROUP COMPOSITION AND GROWTH-REGULATING ACTIVITY OF D-GLUCOSE–M-AMINODENZOIC ACID CONDENSATION PRODUCTS

Structural-group composition is studied, mechanisms of formation are proposed and assessment of plant growth activity of condensation products in D-glucose–m-aminobenzoic acid (m-ABA) system is carried out. Solid product of complete reaction system, formed from initial components as a result of complex reaction combination is fractionated with water, nondialysable component is isolated from water-soluble fraction, studied by methods of elemental analysis, electronic and vibrational spectroscopy, as well as tested as growth regulating agent. According to IR-Fourier spectroscopy, undialysable water-soluble products are characterized by structural-group compositions close to natural humic substances: mainly aliphatic backbone including C=C, C=O, C–O, OH-functions and bounded arylamine fragments (m-ABA). The profile of the electron spectra confirms the presence of sufficiently long chromophores in the structure. Such functionalization provided the necessary ratio in the product structure of the active groups and the aromatic component for the development of humic products growth activity at low concentrations due to optimal polar-hydrophobic interactions at supramolecular association level, which was confirmed experimentally by the evaluation of cucumber seeds growth indices of the "Nezhinsky" variety. Additional spectral studies of seed seedlings allowed to justify the mumbling effect of synthesized products, the maximum effect of which was observed in the area of low (0.0008%) solutions concentrations, which is also characteristic of natural humate’s stimulating influence. Further studies are planned in the direction of studying the effect of synthesized products on individual phases of plant development, as well as estimation of their ecotoxicity and biodegradation ability. The results obtained supposed to be the basis of technological scheme for production of processed humin-like products on an industrial scale.

Effect of the Enantiomeric Ratio of Eutectics on the Results and Products of the Reactions Proceeding with the Participation of Enantiomers and Enantiomeric Mixtures

This perspective is focused on the main parameters determining the results of crystallization of enantiomers or enantiomeric mixtures. It was shown that the ratio of supramolecular and helical associations depends on the eutectic composition of the corresponding enantiomeric mixture. The M and P ratios together with the self-disproportionation (SDE) of enantiomers define the reaction of the racemic compound with the resolving agent. Eventually, each chiral molecule reacts with at least two conformers with different degrees of M and P helicity. The combined effect of the configuration, charge distribution, constituent atoms, bonds, flexibility, and asymmetry of the molecules influencing their behavior was also summarized.

Supramolecular association and quantification of intermolecular interactions of 4′-functionalized 2,2′:6′,2″-terpyridines: Experimental observation and theoretical studies

Three versatile 4′-substituted 2,2′:6′,2″-terpyridine compounds (1–3) having different substitutions (4-ethoxyphenyl, 4-methoxyphenyl and pyridyl) at 4′-position of the central pyridine ring have been synthesized and structurally characterized. Three representative crystal structures have been determined through single crystal X-ray diffraction analysis. X-ray crystallography revels that the structures are stabilized through C–H···π and π–π stacking interactions. In the solid-state, the supramolecular assemblies of the title compounds have been explored in detail. Compounds (1) and (3) exhibits both C–H···π and π–π interactions in building supramolecular assemblies whereas compound (2) exhibit π–π interaction only. All the intermolecular interactions that are involved within the structures are quantified through Hirshfeld surface analyses. The weak noncovalent interactions that played significant role in building supramolecular assemblies are further characterized by Bader's theory of ‘atoms-in-molecules’ (AIM). Finally, the supramolecular networks are characterized by theoretical ‘Noncovalent Interaction’ (NCI) plot index.The supramolecular solid-state frameworks of three 4′-functionalized 2,2′:6′,2″-terpyridine derivatives have been quantified which are further characterized theoretically by the Bader's theory of ‘atoms-in-molecules’(AIM) and ‘noncovalent interaction’ (NCI) plot index.

Humic acid enhances heat stress tolerance via transcriptional activation of Heat-Shock Proteins in Arabidopsis

Humic acid (HA) is composed of a complex supramolecular association and is produced by humification of organic matters in soil environments. HA not only improves soil fertility, but also stimulates plant growth. Although numerous bioactivities of HA have been reported, the molecular evidences have not yet been elucidated. Here, we performed transcriptomic analysis to identify the HA-prompted molecular mechanisms in Arabidopsis. Gene ontology enrichment analysis revealed that HA up-regulates diverse genes involved in the response to stress, especially to heat. Heat stress causes dramatic induction in unique gene families such as Heat-Shock Protein (HSP) coding genes including HSP101, HSP81.1, HSP26.5, HSP23.6, and HSP17.6A. HSPs mainly function as molecular chaperones to protect against thermal denaturation of substrates and facilitate refolding of denatured substrates. Interestingly, wild-type plants grown in HA were heat-tolerant compared to those grown in the absence of HA, whereas Arabidopsis HSP101 null mutant (hot1) was insensitive to HA. We also validated that HA accelerates the transcriptional expression of HSPs. Overall, these results suggest that HSP101 is a molecular target of HA promoting heat-stress tolerance in Arabidopsis. Our transcriptome information contributes to understanding the acquired genetic and agronomic traits by HA conferring tolerance to environmental stresses in plants.

Interplay between structural static and dynamical parameters as a key factor to understand peculiar behaviour of associated liquids

In this article, we have addressed fundamental relationships between the chemical structure, intermolecular order, degree of the association and the dynamical properties, including the nature of dielectric response function, the variation of the glass transition temperature and the Kirkwood factor in three homologues phenyl derivatives of monohydroxy alcohols: 1-phenyl-2-butanol, 4-phenyl-1-butanol, and 4-phenyl-2-butanol. Dielectric data supported by infrared and diffraction investigations allowed us to certify that the Debye relaxation can be detected not only in aliphatic but also aromatic monohydroxy alcohols, suggesting its universal character, irrespectively of the chemical structure and steric hindrance. Moreover, we discovered that besides water, 4-phenyl-1-butanol is a next H-bonded system that exhibits the Debye-like relaxation process and no sign of the diffraction pre-peak being a fingerprint of the medium-range intermolecular order. This finding alters our understanding of the molecular origin of the scattering pre-peak and Debye-type process in diffractograms and dielectric loss spectra, respectively. Finally, we revealed that the activation volume, which is a measure of the volume required for reorientational motions of molecules to occur, is the greatest for the system with the highest Kirkwood factor at the glass transition temperature. It means that except the static parameters characterising the size of the supramolecular associates, their morphology, and the degree of intermolecular order, also dynamical quantity related to the volume of relaxing supramolecular structures is required to understand the fluctuations in the Kirkwood factor, and generally, the behaviour of associating liquids at varying thermodynamic conditions.

Synthesis and Binding of Mannose-Specific Synthetic Carbohydrate Receptors.

Synthetic carbohydrate receptors (SCRs) that selectively recognize cell-surface glycans could be used for detection, drug delivery, or as therapeutics. Here we report the synthesis of seven new C2h symmetric tetrapodal SCRs. The structures of these SCRs possess a conserved biaryl core, and they vary in the four heterocyclic binding groups that are linked to the biaryl core via secondary amines. Supramolecular association between these SCRs and five biologically relevant C1 -O-octyloxy glycans, α/β-glucoside (α/β-Glc), α/β-mannoside (α/β-Man), and β-galactoside (β-Gal), was studied by mass spectrometry, 1 H NMR titrations, and molecular modeling. These studies revealed that selectivity can be achieved in these tetrapodal SCRs by varying the heterocyclic binding group. We found that SCR017 (3-pyrrole), SCR021 (3-pyridine), and SCR022 (2-phenol) bind only to β-Glc. SCR019 (3-indole) binds only to β-Man. SCR020 (2-pyridine) binds β-Man and α-Man with a preference to the latter. SCR018 (2-indole) binds α-Man and β-Gal with a preference to the former. The glycan guests bound within their SCR hosts in one of three supramolecular geometries: center-parallel, center-perpendicular, and off-center. Many host-guest combinations formed higher stoichiometry complexes, 2:1 glycan⋅SCR or 1:2 glycan⋅SCR, where the former are driven by positive allosteric cooperativity induced by glycan-glycan contacts.

(Sub)micron particles forming in aqueous dispersions of amorphous solid dispersions of the poorly soluble drug ABT-199: A combined particle optical counting and field-flow fractionation study

The dispersive behavior of three different amorphous solid dispersion (ASD) formulations of the poorly soluble ABT-199 (Venetoclax) were studied in aqueous and biomimetic media and spontaneously forming supramolecular associates and particles analysed. To this end, the aqueous dispersions were fractionated into a submicron (colloidal) and micrometer-sized particle-fraction by bench-top centrifugation. The submicron fraction was characterized by Asymmetric Flow Field-Flow Fractionation in conjunction with Multi-angle Laser Light Scattering (AF4-MALLS), Dynamic Light Scattering (DLS) and zeta potential analysis. The micron particle fraction was characterized by Single Particle Optical Sensing (SPOS) and light microscopy. Furthermore, drug contents were monitored in terms of total dispersed drug and apparently dissolved drug in the submicron fraction. Despite the fact, that all three formulations showed decent dispersive behavior with almost the complete drug content rapidly dispersed, substantial differences were identified between two of the formulations and the third one: ABT-199/12 and ABT-199/20 showed pronounced precipitation of the drug in form of micrometer particles, a phenomenon described as glass liquid phase separation (GLPS) and only a marginal fraction of the drug was found in the submicron-fraction, i.e. associated with 3 to 4 different supramolecular assemblies (micelles), irrespective whether buffer or fasted state simulated intestinal fluid (FaSSIF) were used as dispersion media. In contrast, ABT-199/40 showed pronounced formation of a wide variety of supramolecular assemblies (micelles) along with substantial association of the drug with all of these, but reduced glass liquid phase separation.

Measuring the Stability of Supramolecular Complexes in the Proximity of Single-Walled Carbon Nanotubes.

Invited for this month's cover is Emilio M. Pérez from IMDEA Nanociencia in Madrid. The cover picture shows the supramolecular association of an ammonium guest to a crown-ether host which is covalently attached to a SWNT. In our manuscript, we show that the corresponding "KPOW!!" would be significantly louder for the binding of the free species in solution, in the absence of the SWNT. Read the full text of their Communication at 10.1002/open.202000018.

Non-covalent protein-based adhesives for transparent substrates-bovine serum albumin vs. recombinant spider silk.

Protein-based adhesives could have several advantages over petroleum-derived alternatives, including substantially lower toxicity, smaller environmental footprint, and renewable sourcing. Here, we report that non-covalently crosslinked bovine serum albumin and recombinant spider silk proteins have high adhesive strength on glass (8.53 and 6.28 MPa, respectively) and other transparent substrates. Moreover, the adhesives have high visible transparency and showed no apparent degradation over a period of several months. The mechanism of adhesion was investigated and primarily attributed to dehydration-induced reorganization of protein secondary structure, resulting in the supramolecular association of β-sheets into a densely hydrogen-bonded network.