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With increasing clinical applications and interest in targeted alpha therapy, there is growing interest in developing alternative chelating agents for [ 212 Pb]Pb 2+ and [ 212/213 Bi]Bi 3+ that exhibit rapid radiolabeling kinetics and kinetic inertness. Herein we report the synthesis and detailed investigation of diacetate and dipicolinate 18- and 21-membered macrocyclic chelators BADA-18, BADA-21, BADPA-18, and BADPA-21 for the complexation of Pb 2+ and Bi 3+ ions with potential use in the preparation of radiopharmaceuticals. The formation of mononuclear complexes was established by using ESI-mass spectrometry, and their stability constants were determined by potentiometric titration. A thorough study of the structure of the metal complexes was carried out by using X-ray diffraction and NMR spectroscopy. It was shown how the stability of the complex is influenced by an increase in the size of the macrocycle, the replacement of acetate arms with picolinate ones, the rigidity of the ligand, as well as the type of conformation ( syn - or anti -) of the metal complex. The new ligands were radiolabeled with [ 210 Pb]Pb 2+ and [ 207 Bi]Bi 3+ , and the in vitro stability of the resulting complexes in a competitive environment of serum and biologically significant metal ions was assessed. Rapid complex formation in 1-2 min at room temperature, as well as the high kinetic inertness of the complexes Pb(BADPA-18) and Bi(BADPA-18) in biological media, demonstrate its potential for use in targeted radionuclide therapy.

Cocrystallization of the dimeric [Cu 2 (μ-I) 2 (CNXyl) 4 ] (Xyl = 2,6-Me 2 C 6 H 3 , 1 ) and polymeric catena -[Cu(μ-I)(CNC 6 H 3 -2-Cl-6-Me) 2 ] ( 2 ) complexes with I 2 at different molar ratios between the reactants resulted in a series of (RNC) 2 CuI-based crystal polyiodides formed along with gradual accumulation of iodine, namely the cocrystals [ 1 ·I 2 ]·[Cu(μ 1,1 -I 3 )(CNXyl) 2 ] 2 followed by the generation of [Cu(μ 1,3 -I 3 )(CNXyl) 2 ] 2 ·2I 2 ( 5 ·2I 2 ) or [Cu(μ 1,1 -I 3 )(CNC 6 H 3 -2-Cl-6-Me) 2 ] 2 and then [Cu(μ 1,3 -I 3 )(CNC 6 H 3 -2-Cl-6-Me) 2 ] n · n / 2 I 2 . The polyiodide 5 ·2I 2 exhibits a novel supramolecular motif─a purely inorganic halogen-bonded Cu 2 (μ 1,3 -I 3 ) 2 core in the chair conformation. The X-ray structure of 5 ·2I 2 featuring I···I contacts was analyzed by a set of theoretical methods and attributed to moderately strong halogen bonding (from -3.2 to -3.9 kcal/mol); these interactions determine the supramolecular architecture of 5 ·2I 2 .

In this work, we synthesized two new benzo-18-azacrown-6 ethers bearing picolinate and pyridine pendant arms and studied the copper complexes of these ligands, as well as those of an acetate analog. All considered ligands were capable of forming mono- and dinuclear complexes due to their large size and large number of donor sites. Among all forms of complexes, the coordination of cations inside the macrocycle has only been shown for the mononuclear form of the acetate complex, while out-cage coordination has been observed for other forms. Electrochemical studies have shown the instability of the mononuclear form of the complex with the pyridine ligand to the reduction in the range of redox potentials of bioreductants. The stabilities of labeled acetate complexes with "in-cage" coordination of the cation and picolinate with "out-cage" coordination were compared in an excess of serum and superoxide dismutase; while the former turned out to be unstable to transchelation, the latter was stable throughout the experiment. Additional studies in biologically relevant media were performed for the picolinate complex and demonstrated its stability in vitro . The biodistribution of this complex in mice after 6 hours post-injection demonstrates a slow excretion from the body; however, the accumulation is noticeably lower than that of free copper cations.

Methods for the synthesis of two types of isomeric dispirocompounds based on imidazothiazolotriazine and pyrrolidineoxindole, differing in the structure of imidazothiazolotriazine fragment, namely, linear dispiro[imidazo[4,5- e ]thiazolo[3,2- b ][1,2,4]triazine-6,3'-pyrrolidine- 4',3″-indolines] and angular dispiro[imidazo[4,5- e ]thiazolo[2,3- c ][1,2,4]triazine-7,3'-pyrrolidine-4',3″-indolines] were proposed. The first method relies on a 1,3-dipolar cycloaddition of azomethine ylides generated in situ from paraformaldehyde and N-alkylglycine derivatives to the corresponding oxindolylidene derivatives of imidazothiazolotriazine. The cycloaddition leads to a mixture of two diastereomers resulted from anti - and syn -approaches of azomethine ylide in approximately a 1:1 ratio, which were separated by column chromatography. Another method consists in rearrangement of linear dispiro[imidazo[4,5- e ]thiazolo[3,2- b ][1,2,4]triazine-6,3'-pyrrolidine-4',3″-indolines] into hitherto unavailable angular dispiro[imidazo[4,5- e ]thiazolo[2,3- c ]-[1,2,4]triazine-7,3'-pyrrolidine-4',3″-indolines] upon treatment with KOH. It was found that the anti -diastereomer of linear type underwent rearrangement into the isomeric angular syn -diastereomer, while the rearrangement of the linear syn -diastereomer gave the angular anti -diastereomer.

Co-crystallization is an elegant technique to tune the physical properties of crystalline solids. In the field of energetic materials, co-crystallization is currently playing an important role in the engineering of crystals with improved performance. Here, based on an analysis of the structural features of the green primary explosive, tetramethylammonium salt of 7-oxo-5-(trinitromethyl)-4,5,6,7-tetrahydrotetrazolo[1,5-a][1,3,5]triazin-5-ide ( 1 ), a co-former such as the powerful secondary explosive, benzotrifuroxan (BTF, 2 ), has been proposed to improve it. Compared to the original 1 , its co-crystal with BTF has a higher detonation pressure and velocity, as well as an initiating ability, while the impact sensitivity and thermal stability remained at about the same level. Both co-formers, 1 and 2 , and co-crystal 3 were characterized by single-crystal X-ray diffraction and their crystal packing was analyzed in detail by the set of approaches, including periodic calculations. In the co-crystal 3 , all intermolecular interactions were significantly redistributed. However, no new types of intermolecular interactions were formed during co-crystallization. Moreover, the interaction energies of structural units in crystals before and after co-crystallization were approximately the same. A similar trend was observed for the volumes occupied by structural units and their densifications. The similar nature of the organization of the crystals of the co-formers and the co-crystal gives grounds to assert that the selected co-formers are an ideal pair for co-crystallization, and the invariability of the organization of the crystals was probably responsible for the preservation of some of their properties.

A new synthetic approach for obtaining previously unknown bis(1,3-azol-2-yl)acetonitriles and bis(1,3-azol-2-yl)methanes has been developed. It is based on 1,3-dipolar cycloaddition between 2-unsubstituted imidazole N -oxides and 2-(1,3-azol-2-yl)-3,3-dimethylacrylonitriles, which are easily available through the condensation of (1,3-azol-2-yl)acetonitriles with acetone. The method allows for the construction of various unsymmetric derivatives based on imidazole, oxazole, thiazole, and 1,3,4-thiadiazole cyclic molecules. Its potential has been demonstrated via the synthesis of 24 diverse derivatives with yields of 29-92%. Bis(1,3-azol-2-yl)acetonitriles can be converted to the corresponding bis(1,3-azol-2-yl)methanes via simple acid hydrolysis followed by subsequent spontaneous decarboxylation at nearly quantitative yields.

An original method for the synthesis of 2-hydrazonoimidazo[4,5- d ]thiazolone derivatives has been developed based on a one-pot acid-induced sequence of hydrazone formation from 3-thioxoperhydroimidazo[4,5- e ]-1,2,4-triazinones and aromatic aldehydes, triazine ring contraction to imidazolidine one, and Dimroth-type N/S-interchange of N -aminothioglycolurils formed in situ into 2-hydrazonoimidazo[4,5- d ]thiazolones. 3-Phenylacroleine derivatives are also suitable substrates for the reaction with thioxoperhydroimidazotriazinones., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Highly diastereoselective methods for the synthesis of two different diastereomers of polynuclear dispiroheterocyclic compounds with five chiral centers comprising pyrrolidinyloxindole and imidazothiazolotriazine moieties (dispiro[imidazo[4,5-e]thiazolo[2,3-c]-1,2,4-triazine-7,3'-pyrrolidine-2',3''-indoles]) have been developed on the basis of a dipolar cycloaddition of azomethine ylides to benzylidene derivatives of imidazothiazolotriazines and an alkali-induced rearrangement of the thiazolotriazine fragment. The different sequence of the cycloaddition and rearrangement stages allows us to perform the targeted synthesis of two diastereomerically pure products from the same starting compounds.

Copper-based radiopharmaceuticals are of high interest these days owing to the decay properties of copper radioisotopes. In contrast, labeled zinc compounds have been less studied for applications in nuclear medicine. In this study, the stability of labeled zinc and copper complexes with two azacrown ether ligands was investigated and compared. Then, the in vitro and in vivo stability of the studied zinc complexes was demonstrated, with the complexes showing promise for biomedical applications. In contrast, analogous copper complexes quickly dissociated in the presence of serum proteins. Furthermore, a simple method for the production of radiochemically pure 65Zn was proposed, and the opportunity for its use as a surrogate radionuclide for research into potential zinc-containing radiopharmaceuticals was demonstrated.

Photochemical oxidative cyclization of 2- and 3-thienylstilbenes (heterostilbenes) containing mono-, di- and trimethoxy groups in the benzene ring or heterocyclic fragment results in the formation of isomeric thieno-annelated polycyclic aromatic compounds demonstrating optical properties that differ from those of initial stilbene derivatives. The structures of cyclic products were evaluated via 1 H and 13 C NMR, HRMS, elemental analysis and X-ray crystallography. The research was aimed to study the effect of substituents in stilbene derivatives of thiophene as well as the position of the styryl fragment in the thiophene nucleus on the occurrence of photocyclization reactions.

Strength of interaction between Bader's atomic basins, enclosed by zero-flux surfaces of electron distribution, was proposed to be a measure of elastic deformation of an interaction. The set containing 53 atomic aggregate and covering all range of interaction strength (from van der Waals interactions to triple covalent bonds) was calculated by DFT and perturbation theory methods. Further analysis was performed to seek correlations between various local quantities based on electron density and effective force constants of stretching diatomic vibrations. The linear trend between effective force constants and the potential energy density at the (3, -1) critical point of electron distribution was found. This correlation was improved by the integration of the potential energy density over an interbasin zero-flux surface of electron density. Simple mechanical explanation of established trends is presented. The correlations can be further used to at least semiquantitatively compare any pair of interactions between Bader's atomic basins.

An effective and highly regio- and diastereoselective one-pot method for the synthesis of new polynuclear dispiroheterocyclic systems with five stereogenic centers (dispiro[imidazo[4,5- e ]thiazolo[3,2- b ]-1,2,4-triazine-6,3'-pyrrolidine-2',3''-indoles]) comprising pyrrolidinyloxindole and imidazo[4,5- e ]thiazolo[3,2- b ]-1,2,4-triazine moieties has been developed. The method relies on a 1,3-dipolar cycloaddition of azomethine ylides generated in situ from isatin derivatives and sarcosine to 6-benzylideneimidazo[4,5- e ]thiazolo[3,2- b ]-1,2,4-triazine-2,7-diones.

Among 3-(2-aminopropyl)-1,2,4-thiadiazole derivatives contatining substitution-ready secondary amino group and exhibiting cytotoxic towards rat C 6 glioma cells three compounds with LD 50 values ranged from 6 to 48 мM were chosen. For these compounds amides with docosahexaenoic acid were synthetised and their cytotoxic activity was studied. It was shown that, although docosahexaenoic acid itself was not toxic for C 6 glioma cells, its addition to the amino derivatives of 1,2,4-thiadiazole increased or decreased resultant cytotoxicity. The effect depended on the structure of 1,2,4-thiadiazole substituents. The obtained data show that the acylation of cytotoxic compounds with docosahexaenoic acid does not necessarily lead to the increase of their activity, but sometimes can inactivate a compound. This fact should be taken into account, especially in the case of anti-cancer drug development.