ATP binding to Nerve Growth Factor (NGF) and pro-Nerve Growth Factor (proNGF): an endogenous molecular switch modulating neurotrophins activity.

ATP has recently been reconsidered as a molecule with functional properties which go beyond its recognized role of the energetic driver of the cell. ATP has been described as an allosteric modulator as well as a biological hydrotrope with anti-aggregation properties in the crowded cellular environment. The role of ATP as a modulator of the homeostasis of the neurotrophins (NTs), a growth factor protein family whose most known member is the nerve growth factor (NGF), has been investigated. The modulation of NTs by small endogenous ligands is still a scarcely described area, with few papers reporting on the topic, and very few reports on the molecular determinants of these interactions. However, a detailed atomistic description of the NTs interaction landscape is of urgent need, aiming at the identification of novel molecules as potential therapeutics and considering the wide range of potential pharmacological applications for NGF and its family members. This mini-review will focus on the unique cartography casting the interactions of the endogenous ligand ATP, in the interaction with NGF as well as with its precursor proNGF. These interactions revealed interesting features of the ATP binding and distinct differences in the binding mode between the highly structured mature NGF and its precursor, proNGF, which is characterized by an intrinsically unstructured domain. The overview on the recent available data will be presented, together with the future perspectives on the field.

Molecular insights into dicationic versus monocationic ionic liquids as a high hydrophobic alternative for the separation of phenol from waters.

The hydrophobic nature of an extractant is particularly critical in the treatment of wastewater. Considering that dicationic ionic liquids (DILs) are likely to be more hydrophobic, a comparative study of the separation of phenol from waters using [NTf2]- based monocationic ionic liquids (MILs) and DILs is carried out both from experimental and theoretical analysis perspectives. Experimental results revealed that DILs exhibited superior extraction ability compared to MILs, with extraction efficiencies of 93.7% and 97.4% using [BMIM][NTf2] and [C6(MIM)2][NTf2]2 as extractants, respectively. The microscopic examination through theoretical calculations elucidated the higher hydrophobicity and extraction efficiency of DILs over MILs. The results indicated that the DIL showed stronger hydrophobicity than the MIL because the hydrogen bond strength between the DIL and water was lower than that of the MIL. Although the hydrogen bond strength between the DIL and phenol was lower than that of the MIL, the stronger van der Waals forces existed between DIL and phenol, so DIL was more efficient in extracting phenol. In addition, the experimental parameters were optimized to provide basic data for application, such as mass ratio of ILs to water, extraction time and temperature, pH, and initial phenol content. Finally, the DILs were recovered using rotary evaporation apparatus, and the results demonstrated that DILs had good recovery and reuse performance. In brief, this work could provide an effective method for the treatment of phenol-containing wastewater. And the revelation of molecular mechanism is expected to positively impact the design of high-performance task-specific ILs.

Interlayer Interactions and Macroscopic Property Calculations of Squaric-Acid-Linked Zwitterionic Covalent Organic Frameworks: Structures, Photocatalytic Carrier Transport, and a DFT Study.

Squaric-acid-linked zwitterionic covalent organic frameworks (Z-COFs), assembled through interlayer interactions, are emerging as potential materials in the field of photocatalysis. However, the study of their interlayer interactions has been largely overlooked. To address this, this work systematically calculated interlayer interactions via density functional theory (DFT) and analyzed the differences in interlayer interactions of different structures of Z-COFs through interlayer slippage, planarity, and an independent gradient model based on the Hirshfeld partition (IGMH). Furthermore, it revealed the relationship between the interactions and the macroscopic photocatalytic carrier transport performance of the material. The results indicated that both preventing interlayer slippage and enhancing planarity can enhance the interlayer interactions of Z-COFs, thereby improving their macroscopic carrier transport performance in photocatalysis.

Efficient and Selective Construction of 41 2 Metalla-links Using Weak C-H⋠⋠⋠Halogen Interactions.

Through a coordination-driven self-assembly method, four 4 1 2 ${4_1^2 }$ metalla-links and one tetranuclear monocycle were constructed with high selectivity and yield by adjusting the substituent species of the building blocks, as evidenced using X-ray crystallographic analysis, electrospray ionization-time-of-flight/mass spectrometry (ESI-TOF/MS), elemental analysis and detailed solution-state nuclear magnetic resonance (NMR) spectroscopy. Based on X-ray crystallographic analysis and independent gradient model analysis, a significant factor leading to the formation of 4 1 2 ${4_1^2 }$ metalla-links was the introduction of F, Cl, Br and I atoms, which generated additional weak C-H⋅⋅⋅X (X=F, Cl, Br and I) interactions. Furthermore, the dynamic conversion of 4 1 2 ${4_1^2 }$ metalla-links to monocyclic rings in methanol solution was systematically investigated using quantitative 1H NMR techniques.

Structural Engineering of Red Luminogens to Realize High Emission Efficiency through ACQ-to-AIE Transformation.

Deep red/near-infrared (NIR, >650 nm) emissive organic luminophores with aggregation-induced emission (AIE) behaviours have emerged as promising candidates for applications in optoelectronic devices and biological fields. However, the molecular design philosophy for AIE luminogens (AIEgens) with narrow band gaps are rarely explored. Herein, we rationally designed two red organic luminophores, FITPA and FIMPA, by considering the enlargement of transition dipole moment in the charge-transfer state and the transformation from aggregation-caused quenching (ACQ) to AIE. The transition dipole moments were effectively enhanced with a "V-shaped" molecular configuration. Meanwhile, the ACQ-to-AIE transformation from FITPA to FIMPA was induced by a methoxy-substitution strategy. The experimental and theoretical results demonstrated that the ACQ-to-AIE transformation originated from a crystallization-induced emission (CIE) effect because of additional weak interactions in the aggregate state introduced by methoxy groups. Owing to the enhanced transition dipole moment and AIE behaviour, FIMPA presented intense luminescence covering the red-to-NIR region, with a photoluminescence quantum yield (PLQY) of up to 38 % in solid state. The promising cell-imaging performance further verified the great potential of FIMPA in biological applications. These results provide a guideline for the development of red and NIR AIEgens through comprehensive consideration of both the effect of molecular structure and molecular interactions in aggregate states.

Infrared Spectroscopy Evidence of Weak Interactions in Frustrated Lewis Pairs Formed by Tris(pentafluorophenyl)borane.

Frustrated Lewis pairs (FLPs) have been widely investigated as promising catalysts due to their metal-free feature and ability to activate small molecules. Since their discovery, many works have been investigating how these Lewis pairs (intermolecular pairs) are held together in an encounter complex. This prompted several studies based on theoretical investigations, but experimental ones are limited yet. In this communication we show evidence of weak intermolecular interactions between Lewis acids and Lewis bases, distinguishing the Lewis adduct from FLPs, by probing fluorine-carbon vibrational modes using infrared spectroscopy. The main evidence is based on the band shifts occurring in FLPs due to weak hydrogen bonds between the hydrogen atoms of the Lewis base and the fluorine atoms of Lewis acid.

A Theoretical Analysis of Interaction Energies and Intermolecular Interactions between Amphotericin B and Potential Bioconjugates Used in the Modification of Nanocarriers for Drug Delivery.

Amphotericin B (AmB) is an antibiotic with a wide spectrum of action and low multidrug resistance, although it exhibits self-aggregation, low specificity, and solubility in aqueous media. An alternative for its oral administration is its encapsulation in polymers modified with bioconjugates. The aim of the present computational research is to determine the affinity between AmB and six bioconjugates to define which one could be more suitable. The CAM-B3LYP-D3/6-31+G(d,p) method was used for all computational calculations. The dimerization enthalpy of the most stable and abundant systems at pH = 7 allows obtaining this affinity order: AmB_1,2-distearoyl-sn-glycerol-3-phosphorylethanolamine (DSPE) > AmB_γ-cyclodextrin > AmB_DSPEc > AmB_retinol > AmB_cholesterol > AmB_dodecanol, where DSPEc is a DSPE analog. Quantum theory of atoms in molecules, the non-covalent interactions index, and natural bond orbital analysis revealed the highest abundance of noncovalent interactions for AmB-DSPE (51), about twice the number of interactions of the other dimers. Depending on the interactions' strength and abundance of the AmB-DSPE dimer, these are classified as strong: O-H---O (2), N-H---O (3) and weak: C-H---O (25), H---H (18), C-H---C (3). Although the C-H---O hydrogen bond is weak, the number of interactions involved in all dimers cannot be underestimated. Thus, non-covalent interactions drive the stabilization of copolymers, and from our analysis, the most promising candidates for encapsulating are DSPE and γ-cyclodextrin.

Nickel-Catalyzed Asymmetric Hydrogenation of α-Substituted Vinylphosphonates and Diarylvinylphosphine Oxides.

Chiral α-substituted ethylphosphonate and ethylphosphine oxide compounds are widely used in drugs, pesticides, and ligands. However, their catalytic asymmetric synthesis is still rare. Of the only asymmetric hydrogenation methods available at present, all cases use rare metal catalysts. Herein, we report an efficient earth-abundant transition-metal nickel catalyzed asymmetric hydrogenation affording the corresponding chiral ethylphosphine products with up to 99 % yield, 96 % ee (enantiomeric excess) (99 % ee, after recrystallization) and 1000 S/C (substrate/catalyst); this is also the first study on the asymmetric hydrogenation of terminal olefins using a nickel catalyst under a hydrogen atmosphere. The catalytic mechanism was investigated via deuterium-labelling experiments and calculations which indicate that the two added hydrogen atoms of the products come from hydrogen gas. Additionally, it is believed that the reaction involves a NiII rather than Ni0 cyclic process based on the weak attractive interactions between the Ni catalyst and terminal olefin substrate.

Narrow-Pore Engineering of Vinylene-Linked Covalent Organic Frameworks with Weak Interaction-Triggered Multiple Responses.

Vinylene-linked covalent organic frameworks (COFs) are emerging as promising crystalline materials, but their narrow pore engineering is severely impeded by the weak reversibility of the carbon-carbon double bond formation reaction, which has led to less exploration of their ultramicroporous structures and properties. Herein, we developed a single aromatic ring-based tetratopic monomer, tetramethylpyrazine, which undergoes a smooth Knoevenegal condensation at its four arylmethly carbon atoms with linear aromatic dialdehyde monomers upon the self-catalyzed activation of pyridine nitrogen-containing monomers in the presence of an organic anhydride. This has resulted in the formation of two vinylene-linked COFs, which both crystallized in orthorhombic lattices, and layered in AA stacking fashions along the vertical directions. They exhibit high surface areas and well-tailored ultramicropore sizes up to 0.5 nm. The unique cross-linking mode at two pairs of para-positions of each pyrazine unit through carbon-carbon double bonds afford them with π-extended conjugation over the in-plane backbones and substantial semiconducting characters. The resultant COFs can be well-dispersed in water to form stable sub-microparticles with negative charges (zeta potentials: ca. -30 mV), and exhibiting tunable aggregation behaviors through protonation/deprotonation. As a consequence, they exhibit pore-size-dependent colorimetric responses to various anions with different pKa values in high selectivity.

Influence of conventional hydrogen bonds in the intercalation of phenanthroline derivatives with DNA: The important role of the sugar and phosphate backbone.

The influence of hydrogen bonds in model intercalated systems between guanine-cytosine and adenine-thymine DNA base pairs (bps) was analyzed with the popular intercalator 1,10-phenanthroline (phen) and derivatives obtained by substitution with OH and NH2 groups in positions 4 and 7. Semiempirical and Density Functional Theory (DFT) methods were used both including dispersion effects: PM6-DH2, M06-2X and B3LYP-D3 along with the recently developed near linear-scaling coupled cluster method DLPNO-CCSD(T) for benchmark calculations. Our results given by QTAIM and non-covalent interaction analysis confirmed the existence of hydrogen bonds created by OH and NH2 . The trends in the energy decomposition analysis for the interaction energy, ΔEint , showed that the ΔEelstat contributions are equal or even a little bit higher than the values for ΔEdisp . Such important ΔEelstat attractive contribution comes mainly from the conventional hydrogen bonds formed by OH and NH2 functional groups with DNA not only with bps but specially with the sugar and phosphate backbone. This behavior is very different from that of phen and other classical intercalators that cannot form conventional hydrogen bonds, where the ΔEdisp is the most important attractive contribution to the ΔEint . The inclusion of explicit water molecules in molecular dynamics simulations showed, as a general trend, that the hydrogen bonds with the bps disappear during the simulations but those with the sugar and phosphate backbone remain in time, which highlights the important role of the sugar and phosphate backbone in the stabilization of these systems.

An Incremental System To Predict the Effect of Different London Dispersion Donors in All-meta-Substituted Azobenzenes.

Predictive models based on incremental systems exist for many chemical phenomena, thus allowing easy estimates. Despite their low magnitude in isolated systems London dispersion interactions are ubiquitous in manifold situations ranging from solvation to catalysis or in biological systems. Based on our azobenzene system, we systematically determined the London dispersion donor strength of the alkyl substituents Me, Et, iPr up to tBu. Based on this data, we were able to implement an incremental system for London dispersion for the azobenzene scheme. We propose an equation that allows the prediction of the effect of change of substituents on London dispersion interactions in azobenzenes, which has to be validated in similar molecular arrangements in the future.

Current Trends in Computational Quantum Chemistry Studies on Antioxidant Radical Scavenging Activity.

The antioxidative nature of chemicals is now routinely studied using computational quantum chemistry. Scientists are constantly proposing new approaches to investigate those methods, and the subject is evolving at a rapid pace. The goal of this review is to collect, consolidate, and present current trends in a clear, methodical, and reference-rich manner. This paper is divided into several sections, each of which corresponds to a different stage of elaborations: preliminary concerns, electronic structure analysis, and general reactivity (thermochemistry and kinetics). The sections are further subdivided based on methodologies used. Concluding remarks and future perspectives are presented based on the remaining elements.

A Selenide Catalyst for the Activation of Alkenes through Se⋠⋠⋠π Bonding.

Chalcogen bonding catalysis with divalent chalcogenides required using heteroatoms as electron donors to give reactivity, while the activation of hydrocarbons such as alkenes by this concept remains an unresolved challenge. Herein, we discovered a powerful selenide catalyst that showed unprecedented capability in the activation of alkenes. The Se⋅⋅⋅π interactions were capable of catalyzing a broad range of transformations, including intermolecular cyclization and coupling reactions. Significantly, the Se⋅⋅⋅π bonding activation mode can be exploited to achieve intermolecular enyne cyclizations and controlled cross-coupling of triple alkenes. The activation of alkenes by divalent selenides opens up a new avenue for supramolecular catalysis.

Interactions in Ternary Aqueous Solutions of NMA and Osmolytes-PARAFAC Decomposition of FTIR Spectra Series.

Intermolecular interactions in aqueous solutions are crucial for virtually all processes in living cells. ATR-FTIR spectroscopy is a technique that allows changes caused by many types of such interactions to be registered; however, binary solutions are sometimes difficult to solve in these terms, while ternary solutions are even more difficult. Here, we present a method of data pretreatment that facilitates the use of the Parallel Factor Analysis (PARAFAC) decomposition of ternary solution spectra into parts that are easier to analyze. Systems of the NMA-water-osmolyte-type were used to test the method and to elucidate information on the interactions between N-Methylacetamide (NMA, a simple peptide model) with stabilizing (trimethylamine N-oxide, glycine, glycine betaine) and destabilizing osmolytes (n-butylurea and tetramethylurea). Systems that contain stabilizers change their vibrational structure to a lesser extent than those with denaturants. Changes in the latter are strong and can be related to the formation of direct NMA-destabilizer interactions.

New Insights on the Interaction of Phenanthroline Based Ligands and Metal Complexes and Polyoxometalates with Duplex DNA and G-Quadruplexes.

This work provides new insights from our team regarding advances in targeting canonical and non-canonical nucleic acid structures. This modality of medical treatment is used as a form of molecular medicine specifically against the growth of cancer cells. Nevertheless, because of increasing concerns about bacterial antibiotic resistance, this medical strategy is also being explored in this field. Up to three strategies for the use of DNA as target have been studied in our research lines during the last few years: (1) the intercalation of phenanthroline derivatives with duplex DNA; (2) the interaction of metal complexes containing phenanthroline with G-quadruplexes; and (3) the activity of Mo polyoxometalates and other Mo-oxo species as artificial phosphoesterases to catalyze the hydrolysis of phosphoester bonds in DNA. We demonstrate some promising computational results concerning the favorable interaction of these small molecules with DNA that could correspond to cytotoxic effects against tumoral cells and microorganisms. Therefore, our results open the door for the pharmaceutical and medical applications of the compounds we propose.

Temporal stability vs. community matrix measures of stability and the role of weak interactions.

Relationships between different measures of stability are not well understood in part because empiricists and theoreticians tend to measure different aspects and most studies only explore a single form of stability. Using time-series data from experimental plankton communities, we compared temporal stability typically measured by empiricists (coefficient of variation in biomass) to stability measures typically measured by theoreticians derived from the community matrix (asymptotic resilience, initial resilience and intrinsic stochastic invariability) using first-order multivariate autoregressive models (MAR). Community matrices were also used to derive estimates of interaction strengths between plankton groups. We found no relationship between temporal stability and stability measures derived from the community matrix. Weaker interaction strengths were generally associated with higher stability for community matrix measures of stability, but were not consistently associated with higher temporal stability. Temporal stability and stability measures derived from the community matrix stability appear to represent different aspects of stability reflecting the multi-dimensionality of stability.

Disentanglement of orthogonal hydrogen and halogen bonds via natural orbital for chemical valence: A charge displacement analysis.

As known, the electron density of covalently bound halogen atoms is anisotropically distributed, making them potentially able to establish many weak interactions, acting at the same time as halogen bond donors and hydrogen bond acceptors. Indeed, there are many examples in which the halogen and hydrogen bond coexist in the same structure and, if a correct bond analysis is required, their separation is mandatory. Here, the advantages and limitations of coupling the charge displacement analysis with natural orbital for chemical valence method (NOCV-CD) to separately analyze orthogonal weak interactions are shown, for both symmetric and asymmetric adducts. The methodology gives optimal results with intermolecular adducts but, in the presence of an organometallic complex, also intramolecular interactions can be correctly analyzed. Beyond the methodological aspects, it is shown that correctly separate and quantify the interactions can give interesting chemical insights about the systems.

Shedding Light on the Interactions of Hydrocarbon Ester Substituents upon Formation of Dimeric Titanium(IV) Triscatecholates in DMSO Solution.

The dissociation of hierarchically formed dimeric triple lithium bridged triscatecholate titanium(IV) helicates with hydrocarbyl esters as side groups is systematically investigated in DMSO. Primary alkyl, alkenyl, alkynyl as well as benzyl esters are studied in order to minimize steric effects close to the helicate core. The 1 H NMR dimerization constants for the monomer-dimer equilibrium show some solvent dependent influence of the side chains on the dimer stability. In the dimer, the ability of the hydrocarbyl ester groups to aggregate minimizes their contacts with the solvent molecules. Due to this, most solvophobic alkyl groups show the highest dimerization tendency followed by alkenyls, alkynyls and finally benzyls. Furthermore, trends within the different groups of compounds can be observed. For example, the dimer is destabilized by internal double or triple bonds due to π-π repulsion. A strong indication for solvent supported London dispersion interaction between the ester side groups is found by observation of an even/odd alternation of dimerization constants within the series of n-alkyls, n-Ω-alkenyls or n-Ω-alkynyls. This corresponds to the interaction of the parent hydrocarbons, as documented by an even/odd melting point alternation.

Rivalry between Regium and Hydrogen Bonds Established within Diatomic Coinage Molecules and Lewis Acids/Bases.

A theoretical study of the complexes formed by Ag2 and Cu2 with different molecules, XH (FH, ClH, OH2 , SH2 , HCN, HNC, HCCH, NH3 and PH3 ) that can act as hydrogen-bond donors (Lewis acids) or regium-bond acceptors (Lewis bases) was carried out at the CCSD(T)/CBS computational level. The heteronuclear diatomic coinage molecules (AuAg, AuCu, and AgCu) have also been considered. With the exception of some of the hydrogen-bonded complexes with FH, the regium-bonded binary complexes are more stable. The AuAg and AuCu molecules show large dipole moments that weaken the regium bond (RB) with Au and favour those through the Ag and Cu atoms, respectively.

Nanoparticle Mobility over a Surface as a Probe for Weak Transient Disordered Peptide-Peptide Interactions.

Weak interactions form the core basis of a vast number of biological processes, in particular, those involving intrinsically disordered proteins. Here, we establish a new technique capable of probing these weak interactions between synthetic unfolded polypeptides using a convenient yet efficient, quantitative method based on single particle tracking of peptide-coated gold nanoparticles over peptide-coated surfaces. We demonstrate that our technique is sensitive enough to observe the influence of a single amino acid mutation on the transient peptide-peptide interactions. Furthermore, the effects of buffer salinity, which are expected to alter weak electrostatic interactions, are also readily detected and examined in detail. The method presented here has the potential to evaluate, in a high-throughput manner, weak interactions for a wide range of disordered proteins, polypeptides, and other biomolecules.