Many proteins form paralogous multimers - molecular complexes in which evolutionarily related proteins are arranged into specific quaternary structures. Little is known about the mechanisms by which they acquired their stoichiometry (the number of total subunits in the complex) and heterospecificity (the preference of subunits for their paralogs rather than other copies of the same protein). Here we use ancestral protein reconstruction and biochemical experiments to study historical increases in stoichiometry and specificity during the evolution of vertebrate hemoglobin (Hb), a α2β2 heterotetramer that evolved from a homodimeric ancestor after a gene duplication. We show that the mechanisms for this evolutionary transition was simple. One hydrophobic substitution in subunit β after the gene duplication was sufficient to cause the ancestral dimer to homotetramerize with high affinity across a new interface. During this same interval, a single-residue deletion in subunit α at the older interface conferred specificity for the heterotetrameric form and the trans-orientation of subunits within it. These sudden transitions in stoichiometry and specificity were possible because the interfaces in Hb are isologous - involving the same surface patch on interacting subunits, rotated 180° relative to each other - but the symmetry is slightly imperfect. This architecture amplifies the impacts of individual mutations on stoichiometry and specificity, especially in higher-order complexes, and allows single substitutions to differentially affect heteromeric vs homomeric interactions. Many multimers are isologous, and symmetry in proteins is always imperfect; our findings therefore suggest that elaborate and specific molecular complexes may often evolve via simple genetic and physical mechanisms.

In this study, both practical and theoretical aspects of the solubility of edaravone (EDA) in Deep Eutectic Solvents (DESs) were considered. The solubility of edaravone in some media, including water, can be limited, which creates the need for new efficient and environmentally safe solvents. The solubility of EDA was measured spectrophotometrically and the complex intermolecular interactions within the systems were studied with the COSMO-RS framework. Of the four studied DES systems, three outperformed the most efficient classical organic solvent, namely dichloromethane, with the DES comprising choline chloride and triethylene glycol, acting as hydrogen bond donor (HBD), in a 1:2 molar proportion yielding the highest solubility of EDA. Interestingly, the addition of a specific amount of water further increased EDA solubility. Theoretical analysis revealed that in pure water or solutions with high water content, EDA stacking is responsible for self-aggregation and lower solubility. On the other hand, the presence of HBDs leads to the formation of intermolecular clusters with EDA, reducing self-aggregation. However, in the presence of a stoichiometric amount of water, a three-molecular EDA-HBD-water complex is formed, which explains why water can also act as a co-solvent. The high probability of formation of this type of complexes is related to the high affinity of the components, which exceeds all other possible complexes.

Theoretical investigation of thermodynamic stability and bonding features of possible isomers of the molecular and ionic complexes of pyridine with molecular iodine and iodine monochloride IX (X = I,Cl) is presented. M06-2X DFT functional is found to provide bond distances and dissociation energies which are close to those obtained at high-level ab initio CCSD(T)/aug-cc-pvtz//CCSD/aug-cc-pvtz benchmark computations for the most stable isomers, formed via donation of a lone pair of nitrogen atom of pyridine to the iodine atom. These isomers are by 23-33 kJ mol-1 (in case of I2) and by 39-56 kJ mol-1 (in case of ICl) more stable than other molecular complexes. T-shaped π-σ* bonded isomers turn out to be energetically comparable with van der Waals bound compounds. Among the ionic isomers, structures featuring [IPy2]+ cation with I3 - or ICl2 - counterions are more stable. Oligomerization favors ionic isomers starting from the tetrameric clusters of the composition (IX)4Py4.

In recent years, the non-covalent interactions between chalcogen centers have aroused substantial research interest because of their potential applications in organocatalysis, materials science, drug design, biological systems, crystal engineering, and molecular recognition. However, studies on π-hole-type chalcogen∙∙∙chalcogen interactions are scarcely reported in the literature. Herein, the π-hole-type intermolecular chalcogen∙∙∙chalcogen interactions in the model complexes formed between XO2 (X = S, Se, Te) and CH3YCH3 (Y = O, S, Se, Te) were systematically studied by using quantum chemical computations. The model complexes are stabilized via one primary X∙∙∙Y chalcogen bond (ChB) and the secondary C-H∙∙∙O hydrogen bonds. The binding energies of the studied complexes are in the range of -21.6~-60.4 kJ/mol. The X∙∙∙Y distances are significantly smaller than the sum of the van der Waals radii of the corresponding two atoms. The X∙∙∙Y ChBs in all the studied complexes except for the SO2∙∙∙CH3OCH3 complex are strong in strength and display a partial covalent character revealed by conducting the quantum theory of atoms in molecules (QTAIM), a non-covalent interaction plot (NCIplot), and natural bond orbital (NBO) analyses. The symmetry-adapted perturbation theory (SAPT) analysis discloses that the X∙∙∙Y ChBs are primarily dominated by the electrostatic component.

New developments in the field of Lewis acidity are highlighted, with the focus of novel Lewis acids and Lewis superacids of group 2, 13, 14, and 15 elements. Several important basics, illustrated by modern examples (classification of Donor-Acceptor (DA) complexes, amphoteric nature of any compound in terms of DA interactions, reorganization energies of main group Lewis acids and the role of the energies of frontier orbitals) are presented and discussed. It is emphasized that the Lewis acidity phenomena are general and play vital role in different areas of chemistry: from weak \"atomophilic\" interactions to the complexes of Lewis superacids.

The impact of intermolecular copigmentation between five phenolic acids, two flavonoid and three amino acids with R. arboreum anthocyanins (ANS) and its isolated cyanidin-3-O-monoglycosides were investigated through experimental and theoretical approach. On addition of different copigments, phenolic acid induced strong hyperchromic (0.26-0.55 nm) and bathochromic shift (6.6-14.2 nm). The color intensity and stability of ANS with, storage at 4 °C & 25 °C, sunlight, oxidation and heat were evaluated by chromaticity, anthocyanin content, kinetic and structural simulation analysis. The strongest copigmentation reaction was observed with narningin (NA) and also showed high thermostability and highest half-life i.e. 3.39 h-1.24 h at 90-160 °C. The cyanidin-3-O-monoglycosides were analysed for their copigmentation effect and observations revealed that NA displayed best copigmentation effect to cyanidin-3-O-arabinoside (B) followed by cyanidin-3-O-galactoside (A), and cyanidin-3-O-rhamnoside (C). Additionally, structural simulation and steered molecular dynamics insights NA is the most favourable co-pigment involving π-π stacking and H-bonding.

The complex formation of uracil and cytosine with glycyl-L-glutamic acid (β-endorphin 30-31), γ-L-glutamyl-L-cysteinyl-glycine (glutathione reduced), α-L-alanyl-L-tyrosine, and α-L-alanyl-α-L-alanine in a buffered saline has been studied using dissolution calorimetry. The values of the reaction constant, the change in Gibbs energy, enthalpy, and entropy were obtained. It is shown that the ratio of the enthalpy and entropy factors depends on the charge of the peptide ion, and the number of H-bond acceptors in the peptide structure. The contributions of interaction between charged groups and polar fragments, hydrogen bonding, and stacking interaction are discussed, taking into account the effect of solvent reorganization around the reactant molecules.

The advances made in the field of stimuli-responsive catalysis during the last five years with a focus on the novel recently-emerged directions and applications have been surveyed. Metal-free catalysts and organometallic complexes, as well as biomimetic systems and extended structures, which display switchable catalytic activity for a variety of organic transformations, are discussed. Light-activated systems comprised of photochromic molecules capable of modulating reaction rate, yield, or enantioselectivity based on geometric and electronic changes associated with photoisomerization are the focus of the detailed discussion. Alternative stimuli, including pH and temperature, which could be applied either alone or in combination with light, are also addressed. Recent advances clearly demonstrate that the capability to finely tune catalyst behavior via an external stimulus is a powerful tool that could alter the landscape of sustainable chemistry.

Recently an enhancement of the sensitivity of colorectal cancer (CRC) cells by 5-fluorouracil (5FU) due to the concurrent treatment with epigallocatechin-3-gallate (EGCG) has been found. In the present paper, to investigate on this aspect, adenocarcinoma cells HT29 were treated with 5FU, EGCG and an equimolar mixture of 5FU and EGCG ([5FU+EGCG]) and cell viability was determined. While 5FU exhibits a clear activity, EGCG alone does not express any activity. However by treating the cells with [5FU+EGCG] a strong effect of EGCG is evidenced: the sensitivity of HT29 cells to 5FU was increased by 12-fold. A simulation of the behavior of [5FU+EGCG] in different compartments of the gastrointestinal digestion model was also performed. 5FU and EGCG solubilized into a mixture of digestive fluids analyzed by mass spectrometry did not lead to signals of 5FU, EGCG and the related complex, while by diluting the solution they become detectable. On the contrary, when 5FU and EGCG are submitted to the step-by-step digestion model procedure, the analysis did not show the presence of 5FU, EGCG and [5FU+EGCG]. This behaviour could be ascribed to the instability of these compounds due to the too severe digestion conditions and/or to the complexity of the matrix which could lead in ESI conditions to the suppression of the signals of the analytes of interest.

The provitamin A activity of β-carotene is of primary interest to address one of the world\'s major malnutrition concerns. β carotene is a fat-soluble compound and its bioavailability from natural sources is very poor. Hence, studies have been focused on the development of specific core/shell micro- or nano-structures that encapsulate β-carotene in order to allow its dispersion in liquid systems and improve its bioavailability. One key objective when developing these structures is also to accomplish β-carotene stability. The aim of this review is to collect kinetic data (rate constants, activation energy) on the degradation of encapsulated β-carotene in order to derive knowledge on the possibility for these systems to be scaled-up to the industrial production of functional foods. Results showed that most of the nano- and micro-structures designed for β-carotene encapsulation and dispersion in the water phase provide better protection with respect to a natural matrix, such as carrot juice, increasing the β-carotene half-life from about 30 d to more than 100 d at room temperature. One promising approach to increase β-carotene stability was found to be the use of wall material, surfactants, or co-encapsulated compounds with antioxidant activity. Moreover, a successful approach was the design of structures, where the core is partially or fully solidified; alternatively, either the core or the interface or the outer phase are gelled. The data collected could serve as a basis for the rational design of structures for β-carotene encapsulation, where new ingredients, especially the extraordinary natural array of hydrocolloids, are applied.