Vitamin B12 (VB12) – essential nutrient, required for detoxication of homocysteine, support of the myelinization in neural tissue and of the hematopoiesis. Certain drugs (such as antibiotics or antituberculosis drugs) result in deep deficiency of VB12. Using VB12 and its derivatives as antidotes is a promising direction in pharmacology, that allows compensation of the toxic effects of the drugs by nutraceuticals. In the present work, interactions of isoniazid (IZ) (a toxic drug, used in the pharmacotherapy of tuberculosis) with various VB12 derivatives were studied. An in vitro study in aqueous solutions with different pH values showed that the hydrophobic derivative of VB12—heptamethyl ester of aquacyanocobyric acid (ACm) promoted oxidation of IZ and contributed to reducing its hepatotoxicity. The effects of ACm were compared with VB12 and aquacobalamin in a rat model of acute IZ-induced hepatitis. IZ intoxication resulted in higher levels of aspartate aminotransferase (AST). Administration of VB12 and ACm normalized AST levels; treatment with aquacobalamin or ACm normalized total protein levels in blood serum. ACm malsoattenuated bilirubin levels in the blood. All VB12 derivatives significantly reduced lipid peroxidation, which was increased after IZ model was reproduced. Histological analysis confirmed the protective effects of these compounds on the rats’ livers, kidneys, and brains: hepatocyte damage, inflammatory cell infiltration of liver tissues, acute ischemia of the renal cortex, and structural brain damage caused by IZ were all reduced. ACm had more positive effects on the liver than the other two compounds.

Nanostructured layers of poly-4-vinylpyridine (P4VP) are formed at air-water interfaces. Quantitative characteristics of their structure and properties are analyzed within the framework of the model of nanostructured M-monolayer. For the first time, the coordination reaction of poly-4-vinylpyridine with cobalt tetra(p-methoxyphenyl)porphyrinate (CoTpMPP) was carried out in nanostructured layers at the air-water interface. The resulting Langmuir-Schaefer films of P4VP-CoTpMPP were studied by UV-Vis spectroscopy.

Memristive devices offer essential properties to become a part of the next-generation computing systems based on neuromorphic principles. Organic memristive devices exhibit a unique set of properties which makes them an indispensable choice for specific applications, such as interfacing with biological systems. While the switching rate of organic devices can be easily adjusted over a wide range through various methods, controlling the switching potential is often more challenging, as this parameter is intricately tied to the materials used. Given the limited options in the selection conductive polymers and the complexity of polymer chemical engineering, the most straightforward and accessible approach to modulate switching potentials is by introducing specific molecules into the electrolyte solution. In our study, we show polyaniline (PANI)-based device switching potential control by adding nucleotide-free analogue of vitamin B-12, aquacyanocobinamide, to the electrolyte solution. The employed concentrations of this molecule, ranging from 0.2 to 2 mM, enabled organic memristive devices to achieve switching potential decrease for up to 100 mV, thus providing a way to control device properties. This effect is attributed to strong aromatic interactions between PANI phenyl groups and corrin macrocycle of the aquacyanocobinamide molecule, which was supported by ultraviolet-visible spectra analysis.

Recently, we have described the first supermolecular nanoentities of vitamin B-12 derivative, viz. monocyano form of heptabutyl cobyrinate, unique nanoparticles with strong noncovalent intermolecular interactions, emerging optical and catalytic properties. Their nearest analogue, heptamethyl cobyrinate (ACCby), exhibits bioactivity. Here, we demonstrate the first example of the formation of nanoparticles of this nucleotide-free analogue of vitamin B-12 in protein nanocarriers and neuroprotective activity in vivo of the own nanoform of the drug. The preparation and characterization of nanocarriers based on bovine serum albumin (BSA) loaded with vitamin B-12 (viz. cyano- and aquacobalamins) and ACCby were performed. Nucleotide-free analogue of vitamin B-12 is tightly retained by the protein structure and exists in an incorporated state in the form of nanoparticles. The effect of encapsulated drugs on the character and severity of primary generalized seizures in rats induced by the pharmacotoxicant thiosemicarbazide was studied. Cyanocobalamin and ACCby exhibited a neuroprotective effect. The best influence of the encapsulation on the effectiveness of the drugs was achieved in the case of A & Scy;Cby, whose bioavailability as a neuroprotector did not change upon introduction in BSA particles, i.e., 33 % of surviving animals were observed upon ACCby administration in free form and in encapsulated state. No surviving rats were observed without the administration of drugs. Thus, BSA nanocarriers loaded by nanoparticles of nucleotide-free analogues of vitamin B-12,B- including hydrophobic ones, can be recommended for neuroprotection and targeted delivery.

Despite the large number of materials, e.g. semiconducting oxides, carbon nanomaterials, conducting polymers and others, that are used as active layers of chemiresistive sensors to ammonia and hydrogen sulfide, the search for new materials remains an urgent task. Special attention is paid to the search for environmentally friendly materials. Corrinoids are naturally occurring coordination complexes consisting of a central cobalt ion and a tetrapyrrole ligand called a corrin ring. Cobalamins and their derivatives are widely used as active layers of optical and electrochemical sensors. At the same time, vitamin B12 derivatives have not been studied as active layers of chemiresistive gas sensors. In this work, films of two vitamin B12 derivatives, viz. dicyanocobyrinic acid heptabutyl ester (DC) and its aquacyano form, aquacyanocobyrinic acid heptabutyl ester (AC), deposited by spin coating and drop casting techniques onto interdigitated electrodes, were tested for the first time as active layers of chemiresistive sensors for the detection of low concentrations of ammonia and hydrogen sulfide (1–50 ppm) in air. It was shown that films of both vitamin B12 derivatives demonstrated reversible sensor response to NH3 and H2S at room temperature. The limit of detection (LOD) of H2S was 0.1 ppm for both vitamin B12 derivatives, while LOD of ammonia was noticeably lower (0.06 ppm) in the case of AC films than in the case of DC films (0.4 ppm). Both sensors demonstrated a fairly low regeneration time, which did not exceed 180 s for 5 ppm of NH3 and 185 s for 5 ppm of H2S.

Dimethyl sulfoxide (DMSO) is sometimes used as a solvent in the preparation of Langmuir-Blodgett (LB) films. By analogy with standard volatile solvents, it is often assumed that DMSO has no further effect once the solute molecules are distributed over the subphase surface. We hypothesized that this is not always the case and that DMSO may play an important role by remaining on the surface after spreading, contributing to the isotherms, influencing the formation of the LB film, and being incorporated into the resulting film. We studied the spreading of pure DMSO and the properties of Langmuir (spread) and Gibbs (adsorbed) layers of DMSO on water, proposed a robust approach to form the spread layers, and used the LB method to fabricate multilayer films on solid substrates. DMSO, which is completely miscible with water, can itself form a spreading surface layer very similar to the Langmuir layers of insoluble amphiphiles. When transferred repeatedly to a substrate, this layer forms a remarkably stable, poorly soluble multilayer film.

Surface layers of water miscible volatile organic solvents (N,N-dimethylacetamide, acetone, ethanol, and tetrahydrofuran) have been formed on water and their properties have been studied. The layers are stable on the water surface and can be transferred to a solid substrate to form a multilayer film. Despite the volatility of the source material, some films can even withstand heating.

Background. The search for an effective and safe pharmacotherapy for tumor diseases includes the evaluation of the action of candidate molecules on various types of tumor cells. Vitamin B12 and its derivatives are promising molecules whose properties can be controlled through chemical modifications.Objective: conducting in silico chemoreactom screening and in vitro experimental study of aquacobalamin and heptamethyl ester of cyanoaquacobyrinic acid (HECСA).Material and methods. Chemoreactome screening was carried out on the basis of a problem-oriented theory of chemograph isomorphism analysis, which is an extension of the algebraic approach to machine learning and recognition problems. Trainable algorithms for calculating chemical distances between molecules were used, on the basis of which the values of half-maximal inhibitory concentration (IC50) were calculated. Screening was carried out for 470 cultures of human tumor cells, including SNB19 (astrocytoma), HCT116 (colon cancer), HeLa (cervical carcinoma), BT-474 (breast duct carcinoma), and A549 (lung carcinoma) cell lines. Dicyanocobyric acid heptamethyl ester ((CN)2Cby(OCH3)7) was obtained by boiling a solution of vitamin B12 in methanol with sulfuric acid (1.0 M) for 4 days. HECСA ((CN)(H2O)Cby(OCH3)7) was obtained by vacuum drying an aqueous solution of (CN)2Cby(OCH3)7 (pH 4.0 and 25 °С). The ester structure and purity were confirmed by 1H nuclear magnetic resonance data, elemental analysis, and MALDI-ToF (matrix-assisted laser desorption/ionization time of flight) mass spectroscopy. Experimental studies of tumor cell cultures were carried out using the MTT testwith aquacobalamin and HECСA on cell lines of immortalized (telomerized) fibroblasts (Fb-hTERT), lung carcinoma (A549), and breast duct cancer (BT-474).Results. Chemoreactome screening of the effects of molecules on tumor cells made it possible to obtain estimates of cell growth IC50 for 470 tumor cell lines. Depending on cell line and vitamin B12 derivative molecule, IC50 values varied in a fairly wide range: from 15 to 2000 nM. In vitro studies on cultures of two human tumor cell lines (BT-474 and A549) and telomerized Fb-hTERT fibroblasts confirmed the cytotoxic effect of aquacobalamin and its hydrophobic derivative HECСA. It was shown that aquacobalamin had weak cytotoxic properties in the concentration range of 3.125–200 µg/l (IC50 > 200 nM), and HECСA significantly reduces the survival of BT-474 and A549 tumor cell lines at high concentrations (100–200 µg/l, IC50 about 100 nM).Conclusion. Correspondence was shown between the results of in silico chemoreactome screening and in vitro cell culture studies: IC50 values for HECСA were significantly lower than for aquacobalamin, and the conversion factor from chemoreactome estimates to experimental ones was almost the same (2.64 for BT-474, and 2.63 for A549). The results of chemoreactome screening for other tumor cell lines can be used to plan further cell experiments with vitamin B12 derivatives.

Despite the large number of materials, e.g. semiconducting oxides, carbon nanomaterials, conducting polymers and others, that are used as active layers of chemiresistive sensors to ammonia and hydrogen sulfide, the search for new materials remains an urgent task. Special attention is paid to the search for environmentally friendly materials. Corrinoids are naturally occurring coordination complexes consisting of a central cobalt ion and a tetrapyrrole ligand called a corrin ring. Cobalamins and their derivatives are widely used as active layers of optical and electrochemical sensors. At the same time, vitamin B 12 derivatives have not been studied as active layers of chemiresistive gas sensors. In this work, films of two vitamin B 12 derivatives, viz. dicyanocobyrinic acid heptabutyl ester (DC) and its aquacyano form, aquacyanocobyrinic acid heptabutyl ester (AC), deposited by spin coating and drop casting techniques onto interdigitated electrodes, were tested for the first time as active layers of chemiresistive sensors for the detection of low concentrations of ammonia and hydrogen sulfide (1 -50 ppm) in air. It was shown that films of both vitamin B 12 derivatives demonstrated reversible sensor response to NH 3 and H 2 S at room temperature. The limit of detection (LOD) of H 2 S was 0.1 ppm for both vitamin B 12 derivatives, while LOD of ammonia was noticeably lower (0.06 ppm) in the case of AC films than in the case of DC films (0.4 ppm). Both sensors demonstrated a fairly low regeneration time, which did not exceed 180 s for 5 ppm of NH 3 and 185 s for 5 ppm of H 2 S.

Background. The structure of corrin tetrapyrrole macrocycles (compounds similar in structure to vitamin B12) is a kind of universal chemical template for targeted drug delivery, and the development of chemical sensors and antidotes. Objective: systematization of information on targeted modulation of certain corrins’ properties through chemical modifications. Material and methods . Literature analysis using modern methods of topological and metric data analysis was carried out. All relevant publications (n=863) were extracted from the PubMed/MEDLINE database on request “(cobalamin OR Cobyrinic OR vitamin B12) AND (Molecular Conformation [MeSH Terms] OR Vitamin B 12/*analogs & derivatives/*chemistry [MeSH Terms] OR Vitamin B 12/*chemistry [MeSH Terms] OR Structure-Activity Relationship [MeSH Terms])”. Results. Information was systematized on how it is possible to regulate the properties of vitamin B12 (cobalamin) derivatives by introducing specific substitutions of groups in the corrin ring, on chemical modifications of cobalamin derivatives, biosynthetic approaches to the synthesis of cobalamin derivatives, and the effects of interactions of these modified corrins with “small” inorganic and organic molecules. Conclusion. The results obtained by systematic computer analysis of publications on corrins make it possible to reasonably form samples of candidate molecules for corrin studies in silico, in vitro, and in vivo.

Background. Synthetic derivatives of vitamin B12 exhibit various physical, chemical and pharmacological properties. The development of methods for predicting the properties of these molecules based on their chemical structure is important for the targeted organic synthesis of corrins with the desired properties and range of applications in pharmacology. Objective: chemoreactomic assessment of the antioxidant effects of vitamin B12 and its derivatives: aquacobalamin, diaquacobinamide, aquacyano-forms of heptaethanolamine-, heptaethylenediamine-, heptamethyl- and heptabutylcobyrinates. Material and methods. The study was conducted using the method of chemoreactomic analysis, implemented within the framework of the algebraic theory of recognition and topological data analysis and based on the theory of isomorphism of labeled graphs and modern methods for predicting numerical target variables. To carry out chemoinformatic chemoreactome analysis, a special problem-oriented theory was developed within the boundaries of the combinatorial theory of solvability and the antioxidant properties of vitamin B12 derivatives were assessed (140 activities in total). Results. Significant differences were found in the properties of the studied substances in relation to oxidative stress. In test systems based on the oxidant 1,1-diphenyl-2-picrylhydrazyl, at different exposure times to molecules (15–60 min) in different concentrations (10–125 μM, 50–3000 μg/ml), aquacobalamin exhibited the most pronounced antioxidant properties at lower concentrations (up to 100 µM). At higher concentrations of substances (125 μM), the antioxidant activity of other vitamin B12 derivatives was higher. All studied molecules had a moderate antimicronutrient effect (total score of about 3.0; for most synthetic drugs, this score is higher than 3.6). Aquacobalamin was characterized by еhe least pronounced antimicronutrient effect (total score less than 0.8), which indicates an almost complete absence of antivitamin and antimineral action, corresponding to an average increase in the risk of a particular micronutrient excretion by no more than 5%. Conclusion. All the studied compounds exert antioxidant properties to one degree or another. Regardless of the choice of simulated test systems for assessing oxidative stress, aquacobalamin demonstrated antioxidant effects to the greatest extent and practically did not stimulate the loss of other micronutrients.

Objective: to investigate the antitumor effects of various forms of vitamin B12 in combination with various synergistic vitamins and evaluate the prospects for clinical applications. Material and methods. Cell lines BT-474 (breast ductal carcinoma) and A549 (lung carcinoma) were used as an in vitro cell model, and transplantable epidermoid Lewis lung carcinoma (LLC) was used as an in vivo animal tumor model. Animal studies of LLC were carried out on 25 male F 1 hybrid mice (age 2.5–3 months, body weight 23–26 g). In silico research was conducted as a systematic computer analysis of 9,326 scientific sources. Results. In vitro studies on cultures of two human tumor cell lines (BT-474 and A549) confirmed the cytotoxic effect of vitamin B12 (aquacobalamin). It has been shown that vitamin B12 has weak cytotoxic properties in the concentration range of 3.125–200 μg/L (IC50>200 nM), and its hydrophobic derivative (heptamethyl cyanoquacobyric acid ester) significantly reduces the survival of tumor lines. BT-474 and A549 cells at high concentrations (100–200 µg/l, IC50~100 nM). Experimental animals with an in vivo LLС model easily tolerated a drug based on vitamin B12. Exposure to the drug up to the 21 st day of LLС development was accompanied by an increasing tendency to inhibit tumor growth by 10–20% (р=0.059). The results of a systematic in silico review of the literature show that clinical data confirmed the significant antitumor effect of vitamin B12. Conclusion. The cellular model indicated the antitumor properties of vitamin B12 and its hydrophobic derivative. With subchronic intragastric administration of B12 to tumor-bearing animals, a steady tendency to inhibit the LLС growth was observed. Analysis of clinical data confirmed the feasibility of the antitumor use of vitamin B12 individually and in combination with synergistic vitamins.

Nanoarchitectures with promising properties have now been formed from many important biomolecules. However, the preparation of nanoparticles of vitamin B12 and its derivatives remains an ongoing research challenge. This paper describes the formation of supermolecular nanoentities (SMEs) of vitamin B12 derivatives, unique nanoparticles with strong noncovalent intermolecular interactions, emerging properties, and activity. These were created by a nanoarchitectonic approach using directed assembly of layers at the air-water interface as a link in the chain of evolution of the parent molecules under specially created conditions. Such layers can be represented as a nanocosm, where, at a critical density, the assemblies act as nanoreactors in which the transformation of the original material occurs. The discovered SMEs not only replicate the functioning of vitamin B12 assemblies with proteins in living organisms and act as vitamin B12-depended enzymes but also demonstrate important advantages over vitamin B12. They are more efficient in oxygen reduction/evolution reactions and in transformation into other forms. These SMEs, in performing advanced tasks, are an alternative to widely used materials based on noble metals for catalysis, medicine, and environment protection. Our findings open new perspectives both for the fabrication of novel SMEs of biomolecules and for a better understanding of the evolution of biomolecules in nature.

Recently, we have described the first supermolecular nanoentities (SMEs) of a vitamin B12 derivative, viz., a monocyano form of heptabutyl cobyrinate ((CN-)BuCby), unique nanoparticles with strong noncovalent intermolecular interactions, and emerging optical and redox properties. In this work, the fast response of thin films based on the SMEs of the B12 derivative to gaseous toxins (viz., hydrogen cyanide, ammonia, sulfur dioxide, and hydrogen sulfide) particularly dangerous for humans was demonstrated. The reaction between SMEs of (CN-)BuCby in Langmuir-Schaefer (LS) films and HCN generates dicyano species and proceeds ca. 5-fold more rapidly than the process involving drop-coated films that contain (CN-)BuCby in molecular form. The highest sensitivity toward HCN was achieved by using thicker LS films. The reaction proceeds reversibly: upon exposure to air, the dicyano complex undergoes partial decyanation. The decyanated complex retains reactivity toward HCN for at least four subsequent cycles. The processes involving SMEs of (CN-)BuCby and NH3, SO2, and H2S are irreversible, and the sensitivity of the films toward these gases is lower in comparison with HCN. Presented data provides mechanistic information on the reactions involving solid vitamin B12 derivatives and gaseous toxins. In the case of NH3, deprotonation of the coordinated Co(III)-ion water molecule occurs, and the generated hydroxocyano species exhibit high air stability. After binding of SO2, a mixture of sulfito and dicyano species is produced, and the regenerated film contains aquacyano and diaqua or aquahydroxo species, which possess high reactivity toward gaseous toxins. Reaction with H2S produces a mixture of the Co(III)-dicyano form and Co(II)-species containing sulfide oxidation products, which are resistant to aerobic oxidation. Our findings can be used for the development of naked-eye, electronic optic, and chemiresistive sensors toward gaseous toxins with improved reactivity for prompt cyanide detection in air, blood, and plant samples and for analysis of exhaled gases for the diagnosis of diseases.

This review presents a wide range of tetrapyrrole photosensitizers used for photodynamic therapy (PDT), antimicrobial photodynamic therapy, photoinactivation of pathogens. Methods of synthesis and design of new photosensitizers with greater selectivity of accumulation in tumor tissue and increased photoinduced antitumor activity are considered. The issues of studying the properties of new photosensitizers, their photoactivity, the ability to generate singlet oxygen, and the possibility of using targeted photodynamic therapy in clinical practice are discussed. The review examines the work on PDT by national and foreign researchers.

Nanostructured monolayers of zinc octa-tert-butylsulfanyltetrapyrazinoporphyrazinate (ZnSPPz) were obtained at the water-air interface. This compound is characterized by the formation of two types of very stable monolayers: face-on and edge-on. The boundaries of the existence of M-monolayers of various types and the quantitative characteristics of their structure and properties (the size of nanostructures formed in the layer, the number of molecules in them, the distances between them, etc.) are determined. The model, phase diagram, and schemes of monolayers are construct-ed. It is shown that ZnSPPz behaves like a solid solution in the Langmuir-Schafer films obtained from the formed monolayers. The results are of interest for the development and creation of chemical sensors and photoactive thin -film nanomaterials based on ZnSPPz.

Olive leaf extract (OLE) as a rich source of phenolics has numerous health benefits for application in food formulations, nonetheless, it has limitations such as unfavorable sensory attributes, low stability and bioavailability. Correspondingly, in this work, OLE was loaded into reassembled casein micelles (r-CM) as natural nanocarriers. Based on Response Surface Methodology (RSM), optimized conditions for loading were 1.483 mg/mL of OLE, 60 min stirring time at pH = 12, and 20 mM of CaCl2 addition. The optimized carriers were further characterized for morphology, Zeta potential and size along with Fourier-transform infrared (FTIR) spectroscopy, differential scanning calorimetry (DSC), and X-ray diffraction (XRD) analyses. The results illustrated the formation of spherical/ellipsoid nanostructures with an average size of 150 nm and PDI of 0.249 reflecting a moderate size distribution pattern. Moreover, the loaded nanovehicles depicted a negative zeta potential (-36.7 mV). FTIR data portrayed the emergence of a peak at 2358.89 cm(-1) associated with the C-H stretching related to phenolic groups of OLE. DSC thermograms and XRD tests underlined the disappearance of OLE decomposition peak and a low crystallinity after OLE entrapment, respectively. Last but not least, the release test illustrated a controlled release behavior in acidic food simulants, in addition, a Fickian-diffusion-based release mechanism was observed in all the food simulants.

Vitamin B12 (cyanocobalamin) and some of its hydrophilic derivatives are used as antidotes and also to treat megaloblastic anemia, nerve myelination disorders, and liver pathology. This work presents results of a comparative experimental study of cyanocobalamin and its derivatives aquacobalamin and heptamethyl ester of cyanoaquacobyrinic acid. In a model of thiosemicarbazide seizures in rats, aquacobalamin contributed to a lengthening of the seizure latency period while cyanocobalamin contributed to a decrease in the seizure latency period and to a decrease in seizures. Histological study of the brain samples showed that all investigated compounds exhibited an antispasmodic effect as well as neuroprotective and myelinating effects. For the first time it was shown that a derivative of vitamin B12, which has hydrophobic substituents—heptamethyl ester of cyanoaquacobyrinic acid, also exhibits biological activity and, therefore, is of interest for further research. Analysis of changes in the electronic absorption spectra recorded during the interaction of aquacobalamin with thiosemicarbazide indicated possibility of direct interaction of thiosemicarbazide with aquacobalamin.