A.E. Arbuzov Institute of Organic and Physical Chemistry

In this focus article, we provide a scrutinizing analysis of transmission electron microscopy (TEM) and dynamic light scattering (DLS) as the two common methods to study the sizes of nanoparticles with focus on the application in pharmaceutics and drug delivery. Control over the size and shape of nanoparticles is one of the key factors for many biomedical systems. Particle size will substantially affect their permeation through biological membranes. For example, an enhanced permeation and retention effect requires a very narrow range of sizes of nanoparticles (50-200 nm) and even a minor deviation from these values will substantially affect the delivery of drug nanocarriers to the tumour. However, amazingly a great number of research papers in pharmaceutics and drug delivery report a striking difference in nanoparticle size measured by the two most popular experimental techniques (TEM and DLS). In some cases, this difference was reported to be 200-300%, raising the question of which size measurement result is more trustworthy. In this focus article, we primarily focus on the physical aspects that are responsible for the routinely observed mismatch between TEM and DLS results. Some of these factors such as concentration and angle dependencies are commonly underestimated and misinterpreted. We convincingly show that correctly used experimental procedures and a thorough analysis of results generated using both methods can eliminate the DLS and TEM data mismatch completely or will make the results much closer to each other. Also, we provide a clear roadmap for drug delivery and pharmaceutical researchers to conduct reliable DLS measurements.

This review gives a survey of the synthetically useful addition reactions of phosphorus(III) esters (phosphites, phosphonites, phosphinites, amidophosphites, etc. and their thio-analogues) with systems containing carbon-carbon, carbon-oxygen, carbon-nitrogen, nitrogen-nitrogen, nitrogen-oxygen, and nitrogen-sulphur multiple bonds. Products of these reactions are the corresponding derivatives of phosphorus(V) esters (phosphates, phosphonates, phosphinates, etc. and their thio-analogues). Emphasis has been placed on results published within the last ten years. 1. Introduction 2. Addition Reactions to C=C-Systems 2.1. Derivatives of α,β-Unsaturated Carboxylic Acids 2.2.α,β-Unsaturated Carbonyl Compounds 2.3. 1-Alkenephosphonates 2.4. α,β-Unsaturated Nitro Compounds 2.5. Alkenes, Ethynyl Esters, and Halodienes 3. Addition Reactions to C≡C-Systems 4. Addition Reactions to C=O-Systems 4.1. Aldehydes and Ketones 4.2. Activated Carbonyl Compounds 4.3. Carbonyl Compounds and Amines 5. Addition Reactions to C=N- and -C≡N-Systems 5.1. Imines 5.2. Isocyanates and Isothiocyanates 5.3. Cyanides and Isocyanides 6. Addition Reactions to -N=N-, O=N-, and S=N- Systems

-1,4-linked d-galacturonic acid and α-1,2-l-rhamnose units, as well as a variety of neutral sugars such as arabinose, galactose, and lesser amounts of other sugars. Currently, native pectins have been compared to modified ones due to the development of natural medicines and health products. In this review, the results of a study of the bioactivity of pectic polysaccharides, including its various pharmacological applications, such as its immunoregulatory, anti-inflammatory, hypoglycemic, antibacterial, antioxidant and antitumor activities, have been summarized. The potential of pectins to contribute to the enhancement of drug delivery systems has been observed.

Density functional theory methods in combination with vibrational spectroscopy are used to investigate possible variants of molecular structure of the ion pairs of several imidazolium-based ionic liquids (ILs). Multiple stable structures are determined with the anion positioned (a) near to the C2 atom of the imidazolium ring, (b) between N1 and C5, (c) between N3 and C4, and (d) between C4 and C5. Chloride and bromide anions in vacuum also occupy positions above or below the imidazolium ring, but in the condensed state these positions are destabilized. In comparison with the halides that almost equally occupy the positions (a-d), tetrafluoroborate and hexafluorophosphate anions strongly prefer position (a). The position and the type of the anion influence the conformation of the side chains bound to the imidazolium N1 atom, which are able to adopt in vacuum all usual staggered or eclipsed conformations, although in the liquid state some of the conformations are present only as minor forms if at all. Vibrations of the cations depend both on the conformational changes and on the association with the anion. The formation of the ion pairs influences mainly stretching and out-of-plane vibrations of the imidazolium C-H groups and stretching vibrations of the perfluoroanions. Other modes of the ions retain their individuality and practically do not mix. This allows "interionic" vibrations to be separated and to regard the couple of the ions as an anharmonic oscillator. Such a model correlates the molecular structure of various ILs and their melting points without involving the energy of the interaction between the cations and anions but explains structure-melting point correlations on the grounds of quasy-elastic properties.

Diabetes mellitus, an incurable metabolic disease, is characterized by changes in the homeostasis of blood sugar levels, being the subcutaneous injection of insulin the first line treatment. This administration route is however associated with limited patient's compliance, due to the risk of pain, discomfort and local infection. Nanoparticles have been proposed as insulin carriers to make possible the administration of the peptide via friendlier pathways without the need of injection, i.e., via oral or nasal routes. Nanoparticles stand for particles in the nanometer range that can be obtained from different materials (e.g., polysaccharides, synthetic polymers, lipid) and are commonly used with the aim to improve the physicochemical stability of the loaded drug and thereby its bioavailability. This review discusses the use of different types of nanoparticles (e.g., polymeric and lipid nanoparticles, liposomes, dendrimers, niosomes, micelles, nanoemulsions and also drug nanosuspensions) for improved delivery of different oral hypoglycemic agents in comparison to conventional therapies.

Developing new, efficient catalysts that contain Earth-abundant metals and simple, robust ligands for CO 2 hydrogenation is important to create cost-effective processes of CO 2 utilization. Inspired by nature, which utilizes an ortho -OH-substituted pyridine motif in Fe-containing hydrogenases, we developed a Mn complex with a simple N-donor ligand, 6,6′-dihydroxy-2,2′-bipyridine, that acts as an efficient catalyst for CO 2 hydrogenation. Turnover numbers of 6250 for hydrogenation of CO 2 to formate in the presence of DBU were achieved. Moreover, hydrogenation of CO 2 to formamide was achieved in the presence of a secondary amine.

We have studied the dependence of the superconducting (SC) transition temperature on the mutual orientation of magnetizations of Fe1 and Fe2 layers in the spin valve system CoO(x)/Fe1/Cu/Fe2/Pb. We find that this dependence is nonmonotonic when passing from the parallel to the antiparallel case and reveals a distinct minimum near the orthogonal configuration. The analysis of the data in the framework of the SC triplet spin valve theory gives direct evidence for the long-range triplet superconductivity arising due to noncollinearity of the two magnetizations.

Abstract The IR and Raman spectra and conformations of the ionic liquid 1‐ethyl‐3‐methyl‐1 H ‐imidazolium tetrafluoroborate, [EMIM] [BF 4 ] ( 6 ), were analyzed within the framework of scaled quantum mechanics (SQM). It was shown that SQM successfully reproduced the spectra of the ionic liquid. The computations revealed that normal modes of the EMIM + ⋅BF $\rm{_{4}^{-}}$ ion pair closely resemble those of the isolated ions EMIM + and BF $\rm{_{4}^{-}}$ , except for the antisymmetric BF stretching vibrations of the anion, and the out‐of‐plane and stretching vibrations of the HC(2) moiety of the cation. The most plausible explanation for the pronounced changes of the latter vibrations upon ion‐pair formation is the H‐bonding between HC(2) and BF $\rm{_{4}^{-}}$ . However, these weak H‐bonds are of minor importance compared with the Coulomb interactions between the ions that keep them closely associated even in dilute CD 2 Cl 2 solutions. According to the ‘gas‐phase’ computations, in these associates, the BF $\rm{_{4}^{-}}$ anion is positioned over the imidazolium ring of the EMIM + cation and has short contacts not only with the HC(2) of the latter, but also with a proton of the MeN(3) group.

The cycloaddition of CO2 into epoxides catalyzed by imidazolium and related salts continues to attract attention due to the industrial importance of the cyclic carbonate products. The mechanism of the imidazolium-catalyzed transformation has been proposed to require the participation of the acidic C2 proton. However, other simple salts without acidic protons, such as N,N,N,N-tetrabutylammonium chloride, are also efficient catalysts for the reaction. Hence, we decided to investigate the role of the ring protons of imidazolium salts in this reaction. To this end, we systematically studied the catalytic activity of a series of methyl substituted imidazolium cations, in the presence of various halide anions, both by experiment and in silico. Our results demonstrate that, while stabilization of intermediates by C2, C4, or C5 protons in imidazolium salts takes place, it is the nucleophilicity of the anion that governs the overall activity, which is intimately related to the strength of the interactions between the cation and anion. Consequently, the reactivity of the halide anion strongly depends on the nature of the cation and cosolvents. This study completes the (known) mechanism and should facilitate the development of highly efficient catalysts.

The development of biotechnological protocols based on cationic surfactants is a modern trend focusing on the fabrication of antimicrobial and bioimaging agents, supramolecular catalysts, stabilizers of nanoparticles, and especially drug and gene nanocarriers. The main emphasis given to the design of novel ecologically friendly and biocompatible cationic surfactants makes it possible to avoid the drawbacks of nanoformulations preventing their entry to clinical trials. To solve the problem of toxicity various ways are proposed, including the use of mixed composition with nontoxic nonionic surfactants and/or hydrotropic agents, design of amphiphilic compounds bearing natural or cleavable fragments. Essential advantages of cationic surfactants are the structural diversity of their head groups allowing of chemical modification and introduction of desirable moiety to answer the green chemistry criteria. The latter can be exemplified by the design of novel families of ecological friendly cleavable surfactants, with improved biodegradability, amphiphiles with natural fragments, and geminis with low aggregation threshold. Importantly, the development of amphiphilic nanocarriers for drug delivery allows understanding the correlation between the chemical structure of surfactants, their aggregation behavior, and their functional activity. This review focuses on several aspects related to the synthesis of innovative cationic surfactants and their broad biological applications including antimicrobial activity, solubilization of hydrophobic drugs, complexation with DNA, and catalytic effect toward important biochemical reaction.

Surfactants are amphiphilic compounds having hydrophilic and hydrophobic moieties in their structure. They can be of synthetic or of microbial origin, obtained respectively from chemical synthesis or from microorganisms' activity. A new generation of ecofriendly surfactant molecules or biobased surfactants is increasingly growing, attributed to their versatility of applications. Surfactants can be used as drug delivery systems for a range of molecules given their capacity to create micelles which can promote the encapsulation of bioactives of pharmaceutical interest; besides, these assemblies can also show antimicrobial properties. The advantages of biosurfactants include their high biodegradability profile, low risk of toxicity, production from renewable sources, functionality under extreme pH and temperature conditions, and long-term physicochemical stability. The application potential of these types of polymers is related to their properties enabling them to be processed by emulsification, separation, solubilization, surface (interfacial) tension, and adsorption for the production of a range of drug delivery systems. Biosurfactants have been employed as a drug delivery system to improve the bioavailability of a good number of drugs that exhibit low aqueous solubility. The great potential of these molecules is related to their auto assembly and emulsification capacity. Biosurfactants produced from bacteria are of particular interest due to their antibacterial, antifungal, and antiviral properties with therapeutic and biomedical potential. In this review, we discuss recent advances and perspectives of biosurfactants with antimicrobial properties and how they can be used as structures to develop semisolid hydrogels for drug delivery, in environmental bioremediation, in biotechnology for the reduction of production costs and also their ecotoxicological impact as pesticide alternative.

The chemistry of heterocyclic compounds has traditionally been and remains a bright area of chemical science in Russia. This is due to the fact that many heterocycles find the widest application. These compounds are the key structural fragments of most drugs, plant protection agents. Many natural compounds are also derivatives of heterocycles. At present, more than half of the hundreds of millions of known chemical compounds are heterocycles. This collective review is devoted to the achievements of Russian chemists in this field over the last 15–20 years. The review presents the achievements of leading heterocyclists representing both RAS institutes and university science. It is worth noting the wide scope of the review, both in terms of the geography of author teams, covering the whole of our large country, and in terms of the diversity of research areas. Practically all major types of heterocycles are represented in the review. The special attention is focused on the practical applications of heterocycles in the design of new drugs and biologically active compounds, high-energy molecules, materials for organic electronics and photovoltaics, new ligands for coordination chemistry, and many other rapidly developing areas. These practical advances would not be possible without the development of new fundamental transformations in heterocyclic chemistry.<br> Bibliography — 2237 references.

The spin–orbit charge-transfer-induced intersystem crossing (SOCT-ISC) in Bodipy-phenoxazine (BDP-PXZ) compact electron-donor/-acceptor dyads was studied. PXZ is the electron donor, and BDP is the electron acceptor. The molecular geometry is varied by applying different steric hindrance on the rotation about the linker between the two subunits. Charge-transfer (CT) absorption bands were observed for the dyads with more coplanar geometry (electronic coupling matrix elements is up to 2580 cm–1). Ultrafast charge separation (0.4 ps) and slow charge recombination (3.8 ns, i.e., SOCT-ISC process) were observed. Efficient ISC (ΦT = 54%) and long triplet-state lifetime (τT = 539 μs) were observed for the dyads. Notably, the triplet-state lifetime is 2-fold of that accessed with heavy-atom effect, indicating the advantage of using a heavy-atom-free photosensitizer. The low-lying CT state in the dyads in polar solvents was confirmed with intermolecular triplet photosensitizing method. Time-resolved electron paramagnetic resonance spectroscopy show that the electron spin polarization of the triplet state formed by the SOCT-ISC is the same as that of spin–orbit-ISC (SO-ISC). 3CT and localized excited triplet states (3LE) were simultaneously observed for one of the dyads, which is rare. Normally, the CT state was observed as spin-correlated radical pair. The dyads were used as triplet photosensitizers for triplet–triplet annihilation upconversion, the quantum yield is up to 12.3%. A large anti-Stokes shift (5905 cm–1) was achieved by excitation into the CT absorption band, not the conventional LE absorption band.

Dendrimers are well-defined macromolecules whose highly branched structure is reminiscent of many natural structures, such as trees, dendritic cells, neurons or the networks of kidneys and lungs. Nature has privileged such branched structures for increasing the efficiency of exchanges with the external medium; thus, the whole structure is of pivotal importance for these natural networks. On the contrary, it is generally believed that the properties of dendrimers are essentially related to their terminal groups, and that the internal structure plays the minor role of an 'innocent' scaffold. Here we show that such an assertion is misleading, using convergent information from biological data (human monocytes activation) and all-atom molecular dynamics simulations on seven families of dendrimers (13 compounds) that we have synthesized, possessing identical terminal groups, but different internal structures. This work demonstrates that the scaffold of nanodrugs strongly influences their properties, somewhat reminiscent of the backbone of proteins.

Hydrogen bonding in ionic liquids based on the 1-(2'-hydroxylethyl)-3-methylimidazolium cation ([C₂OHmim](+)) and various anions ([A](-)) of differing H-bond acceptor strength, viz. hexafluorophosphate [PF6](-), tetrafluoroborate [BF₄](-), bis(trifluoromethanesulfonimide) [Tf₂N](-), trifluoromethylsulfonate [OTf](-), and trifluoroacetate [TFA](-), was studied by a range of spectroscopic and computational techniques and, in the case of [C₂OHmim][PF6], by single crystal X-ray diffraction. The first quantitative estimates of the energy (E(HB)) and the enthalpy (-ΔH(HB)) of H-bonds in bulk ILs were obtained from a theoretical analysis of the solid-state electron-density map of crystalline [C₂OHmim][PF6] and an analysis of the IR spectra in crystal and liquid samples. E(HB) for OH···[PF6](-) H-bonds amounts to ~3.4-3.8 kcal·mol(-1), whereas weaker H-bonds (2.8-3.1 kcal·mol(-1)) are formed between aromatic C2H group of imidazolium ring and the [PF6](-) anion. The enthalpy of the OH···[A](-) H-bonds follows the order: [PF6] (2.4 kcal·mol(-1)) < [BF₄] (3.3 kcal·mol(-1)) < [Tf₂N] (3.4 kcal·mol(-1)) < [OTf] (4.7 kcal·mol(-1)l) < [TFA] (6.2 kcal·mol(-1)). The formation of aggregates of self-associated [C₂OHmim](+) cations is present in liquid [C₂OHmim][PF6], [C₂OHmim][BF₄], and [C₂OHmim][Tf₂N], with the energy of the OH···OH H-bonds amounting to ~6 kcal·mol(-1). Multiple secondary interactions in the bulk ILs influence their structure, vibrational spectra, and H-bond strength. In particular, these interactions can blue-shift the stretching frequencies of the CH groups of the imidazolium ring in spite of red-shifting CH···[A](-) H-bonds. They also weaken the H-bonding in the IL relative to the isolated ion pairs, with these anticooperative effects amounting to ca. 50% of the E(HB) value.

Relative infrared (IR) intensities and relative Raman activities have been computed for vibrations of test molecules, including from two to nine heavy atoms, using second-order Moller-Plesset perturbation theory (MP2), and three hybrid density functionals (B3LYP, M05, and M05-2X). The basis set convergence of vibrational properties is discussed. Our results demonstrate that B3LYP offers the most cost-effective choice for the prediction of molecular vibrational properties, but the predictions of another two tested hybrid functionals are very similar and in very good agreement with experimental data. MP2 shows good performance for the IR intensities, whereas the quality of prediction of the relative Raman activities should be characterized as only moderate. B3LYP calculations of the relative IR intensities using highly compact Sadlej's Z3PolX basis set retain the high accuracy of the more CPU expensive Sadlej's pVTZ and much more expensive aug-cc-pVTZ calculations. Relative Raman activities are more sensitive to basis set effects and require at least Sadlej's pVTZ to obtain quantitative results.

This paper addresses a review of platinum-based hydrosilylation catalysts. The main field of application of these catalysts is the curing of silicone polymers. Since the 1960s, this area has developed rapidly in connection with the emergence of new polymer compositions and new areas of application. Here we describe general mechanisms of the catalyst activity and the structural effects of the ligands on activity and stability of the catalysts together with the methods for their synthesis.

There is a growing interest in the utilization of metal oxide nanoparticles as antimicrobial agents. This review will focus on titanium dioxide nanoparticles (TiO2 NPs), which have been demonstrated to exhibit high antimicrobial activity against bacteria and fungi, chemical stability, low toxicity to eukaryotic cells, and therefore high biocompatibility. Despite the extensive research conducted in this field, there is currently no consensus on how to enhance the antimicrobial efficacy of TiO2 NPs. The aim of this review is to evaluate the influence of various factors, including particle size, shape, composition, and synthesis parameters, as well as microbial type, on the antibacterial activity of TiO2 NPs against bacteria and fungi. Furthermore, the review offers a comprehensive overview of the methodologies employed in the synthesis and characterization of TiO2 NPs. The antimicrobial activity of TiO2 exhibits a weak dependence on the microorganism species. A tendency towards increased antibacterial activity is observed with decreasing TiO2 NP size. The dependence on the shape and composition is more pronounced. The most pronounced antimicrobial potential is exhibited by amorphous NPs and NPs doped with inorganic compounds. This review may be of interest to specialists in biology, medicine, chemistry, and other related fields.

, ion mobility-mass spectrometry), gas-phase infrared spectroscopy, recognition tunnelling nanopores, and molecular modeling to identify bioactive GAG sequences, biophysical methods to investigate binding interfaces, and to expand our knowledge and understanding of glycocodes governing GAG molecular recognition, and (iii) artificial intelligence for in-depth investigation of GAGomic data sets and their integration with proteomics.

We describe a catalytic system composed of rhodium nanoparticles immobilized in a Lewis acidic ionic liquid. The combined system catalyzes the hydrogenation of quinolines, pyridines, benzofurans, and furan to access the corresponding heterocycles, important molecules present in fine chemicals, agrochemicals, and pharmaceuticals. The catalyst is highly selective, acting only on the heteroaromatic ring, and not interfering with other reducible functional groups.