Novel conjugates of rhodamine B with 2-chloro-, 2-chloro-6-methyl-and 2-chloro-6-methoxyquinoline were synthesized. Their structure and ion-induced switching properties were studied using 1 & Ncy;, COSY, 13 & Scy;, HSQC and HMBC NMR, UV-Vis/fluorescence spectroscopy, X-ray diffraction analysis and DFT quantum chemical calculations. The compounds obtained exist in the spirolactam form, which is characterized by the lack of absorption in the region > 500 nm and the absence of emission properties. However, in the presence of Hg2+ cations, they exhibit a selective and contrasting naked eye effect, as a result of which the colorless acetonitrile solution becomes purple. Simultaneously, the appearance of intense emission at 584-588 nm is observed. These changes are due to the opening of the spirocycle, which was confirmed by an additional 1H NMR experiment. The reverse transformation occurs under the action of CN-anions. The observed ion-controlled off-on-off switching of the fluorescence properties was used to develop the logic circuit. For the first time, using PCM/DFT/M06-2X-D3/ Def2-SVP calculations in acetonitrile and AIM analysis, it was shown that the interaction with mercury(II) cations is a multistage process.

It has been shown that the oxidative transformation of 4H-pyrans into pyrylium salts is accompanied by a structural rearrangement of the resulting pyrylium cations. The reaction of 4-substituted 3-formyl-2,6-diphenyl-4H-pyrans with trityl perchlorate in 1,2-dichloroethane affords either the expected 3-formylpyrylium salts or isomeric 5-benzoylpyrylium cations. The reaction pathway depends on the temperature and the steric bulk of the substituent at position 4 of the pyran ring. DFT calculations that account for solvation effects (PCM model, 1,2-dichloroethane) and the Grimme dispersion correction (D3) suggested that, in the presence of catalytic amounts of HClO4, the isomerization of 3-formylpyrylium cations proceeds through a multistep ANRORC-type mechanism initiated by nucleophilic attack of a water molecule. Thus, a simple change in oxidation conditions reveals a previously unknown rearrangement channel of pyrylium cations during oxidative dehydrogenation and allows the selective preparation of two series of structurally distinct pyrylium salts from the same 4H-pyran precursor.

The photochromic behavior of N-acetyl (2) and N-propionyl (3) derivatives of 2-((phenylamino)methylene)benzo[b]thiophen-3(2H)-one was investigated in both the solid state and in solution using IR, 1H, 13C NMR spectroscopy, high-resolution mass spectrometry, UV-Vis/fluorescence spectroscopy, and X-ray diffraction analysis, complemented by DFT quantum chemical calculations. Solid-state irradiation of N-acetyl derivative 2 triggers [2+2] photocycloaddition to yield dimer 4, whereas the N-propionyl analog 3 remains photostable under these conditions. Conversely, in acetonitrile solution, irradiation of both 2 and 3 with light of 436 nm induces a multi-step 1,5-sigmatropic N→O acyl migration, resulting in the formation of O-acetyl 5 and O-propionyl 6 isomers. DFT calculations at the M06-2X/Def2-TZVP level, incorporating the PCM solvation model and AIM analysis, were successfully utilized to rationalize the observed phase-dependent photochemical phenomena.

New F16 derivatives – (E)-4-(1H-indol-3-ylvinyl)-N-alkylpyridinium salts containing phenyl substituents on the pyridine ring were prepared by the reaction of (E)-4-(1-(1-methyl-1H-indol-3-yl)prop-1-en-2-yl)-2,6-diphenylpyrylium perchlorate with amines. The use of pyrylium salts as starting compounds is an advantage over traditional F16 syntheses, based on the reactions of pre-synthesized pyridines, since it allows the introduction of any aromatic and/or aliphatic substituents into the pyridine ring. The obtained compounds exhibit properties of dual-state emission (DSE). The extremely low fluorescence quantum yields in solution (ϕf ≤ 0.004) significantly limit their practical applications. However, the substantially higher quantum yields observed in the solid state (ϕf = 0.023–0.045) suggest their potential utility for imaging in aggregated or membrane-bound systems. Photoinitiated processes in F16 derivatives, along with the fluorescence of the original E-isomeric forms, include photochromism, which allows them to be considered as fluorescent molecular switches. The optical properties of one of the compounds allow it to be used to assess membrane potential in isolated mitochondria and observe its accumulation in mitochondria of living cells by fluorescent microscopy. A comparison of the penetration of the lipophilic cations, both those obtained in this study and known in the literature, through an artificial lipid bilayer membrane in response to the application of a transmembrane electrical potential is carried out.

New photo- and ionochromic N-acylated 2-(aminomethylene)benzo[b]thiophen-3(2H)-ones containing a terpyridine receptor have been synthesized. They absorb in the visible region of the spectrum at 423-426 nm and exhibit emission at 463-468 nm. Their irradiation in acetonitrile with light of 436 nm leads to a multi-stage rearrangement, including Z/E isomerization about the C--C bond, N -> O migration of the acyl group and the formation of non-emissive O-acylated E-isomers, which were isolated preparatively. Their structure was established unambiguously by IR, 1H, 13C NMR spectroscopy and HR mass spectrometry. The reverse thermal reaction with O -> N migration of the acyl group is catalyzed by acid catalysts. N-Acylated compounds in acetonitrile selectively form non-fluorescent complexes with Fe2+ cations, which is accompanied by the naked-eye effect with changing the color from yellow to maroon. A successful selective interaction with AcO- led to the restoration of the initial absorption and emission properties. Density functional theory (DFT) calculations at the M06-2X/def2TZVP level with the PCM solvation method were used to explain the observed photoisomerizations and ionochromic transformations. The obtained compounds represent multifunctional on-off-on molecular switches of optical and fluorescent properties upon sequential exposure to light and H+ or sequential addition of Fe2+ and AcO- ions. A combinatorial logic gate was designed based on the basis of these switching properties.

The potential energy surfaces (PESs) for a number of reactions between substituted acetylenes and substituted 2H-thiopyran-2-thiones, as well as their isoelectronic analogues were studied by PCM/DFT/B3LYP/6-311++G(d,p) quantum chemical calculations. Theoretical studies have revealed the similarity of the PESs, which differ from each other only in their energetic characteristics. Similar reaction channels on these surfaces lead to different products through six similar minimum-energy pathways (MEPs). In the case of an excess of acetylene, the formation of 4-thiophene-substituted thiopyran derivatives is energetically preferred.

The efficiency of combining experimental methods and quantum chemical calculations (DFT and ab initio) for optimizing conditions and predicting mechanisms for the interaction of acyclic and cyclic derivatives of indole‐2,3‐quinodimethane with heterodienophiles is demonstrated. For the reactions of acyclic derivatives of indole‐2,3‐quinodimethane with nitriles and carbon disulfide, indoles, [b]‐fused with nitrogen‐ and sulfur‐containing six‐membered rings, were synthesized. Quantum chemistry methods have shown that the addition of nitriles and carbon disulfide to indole‐2,3‐quinodimethane derivatives occurs through cyclic transition states involving a lithium atom. Calculations have substantiated the choice of a non‐polar aprotic solvent to increase the yield of γ‐carbolines. It has been shown for the first time that the replacement of the oxygen atom in cyclic derivatives of quinodimethane—pyrano[4,3‐b]indol‐3(5H)‐ones by sulfur leads to a complete change in the direction and mechanism of their reaction with dimethyl acetylenedicarboxylate: instead of the usual [4+2] cycloaddition in the case of an oxygen‐containing substrate, cascade processes are realized, including alkyne‐thiocarbonyl metathesis and [3+2] cycloaddition.

Bifunctional hybrids of a new type containing photochromic indolyl(thienyl) diarylethenes with a pyrroldione bridge directly linked by a dimethylene spacer to an ionochromic rhodamine moiety were synthesized. The synthesized hybrids in toluene exhibit absorption at 450-455 nm and fluorescence at 560 nm. Irradiation with UV light leads to the formation of ring-closed non-fluorescent diarylethene isomeric fragments. Under visible light (or gradually in the dark conditions), reverse isomerization to the initial forms occurs. The spectral and kinetic characteristics of the processes have been studied. In the presence of H+ cation, a striking naked eye effect is observed due to the opening of the rhodamine-spirolactam ring and appearance of a characteristic pink-crimson coloration at 561 nm along with intense long-wavelength emission at 586 nm. This process is completely reversible upon exposure to triethylamine. The mechanism of this transformation was confirmed by additional 1H and 13C NMR experiments. The M06-2X/Def2-TZVP method and AIM analysis were successfully used to explain observed light-induced isomerizations as well as proton-induced transformations. Thus, revers-ible switching of the fluorescent properties of hybrid molecules can be operated by light irradiation and proton.

Six previously unknown zwitterions with positively and negatively charged [NHN] hydrogen bonds were synthesized by acylation of 4,5-bis(dimethylamino)-1-tosylamino-8-aminonaphthalene with subsequent alkaline treatment of the resulting 8-acylamino derivatives. Using NMR and XRD measurements in conjunction with quantum chemical DFT/PBE1PBE/6-311++G(d,p) calculations, it was shown that the negatively charged [NHN](-) bond in such compounds commonly differs from the [NHN](+) bond by significantly lower linearity, higher asymmetry, and moderate to strong paramagnetic shift of the chelated NH proton signal. Among other remarkable findings, the most important are (1) unusually high polarity (mu = 21-26 D) of the obtained zwitterions, (2) sharp difference in structures of the solid 1,8-bis(tosylated) zwitterion (BTZ) grown from MeCN or DMF, and (3) registration for one of the stereoisomers of BTZ with the record short [NHN](-) hydrogen bridge (NN = 2.510 & Aring;) almost reaching the theoretical limit (2.50 & Aring;) for the [NHN](+) hydrogen bond.

While it is well established that a mere 2% of human DNA nucleotides are involved in protein coding, the remainder of the DNA plays a vital role in the preservation of normal cellular genetic function. A significant proportion of tandem repeats (TRs) are present in non-coding DNA. TRs - specific sequences of nucleotides that entail numerous repetitions of a given fragment. In this study, we employed our novel algorithm grounded in finite automata theory, which we refer to as Dafna, to investigate for the first time the likelihood of these nucleotide sequences forming non-canonical DNA structures (NS). Such structures include G-quadruplexes, i-motifs, hairpins, and triplexes. The tandem repeats under consideration in our research encompassed sequences containing 1 to 6 nucleotides per repeated fragment. For comparison, we employed a set of randomly generated sequences of the same length (60 nucleotides) as a benchmark. The outcomes of our research exposed a disparity between the potential for NS formation in random sequences and tandem repeats. Our findings affirm that the propensity of DNA and RNA to form NS is closely tied to various genetic disorders, including Huntington's disease, Fragile X syndrome, and Friedreich's ataxia. In the concluding discussion, we present a proposal for a new therapeutic mechanism to address these diseases. This novel approach revolves around the ability of specific nucleic acid fragments to form multiple types of NS.

The possibility of synthesizing 12-(aryldiazo)berberrubines was demonstrated experimentally and by quantum-chemical calculations based on the Density Functional Theory in the B3LYP/6-31G(d,p) basis set. In weakly alkaline media, berberrubine can be substituted at position 12 by azo coupling reactions with aryldiazonium salts. This process proceeds in steps: first, berberrubine transforms into the zwitterionic form of 9-oxoberberine, which then enters as a nucleophile into an azo coupling reaction with aryldiazonium salts to form a single product with the trans configuration of the fragments relative to the N=N double bond. The resulting 12-(aryldiazo)berberrubines may find use as antibiotic agents, as shown on the multidrug-resistant culture Acinetobacter lwoffii .

Reaction of thiopyrano[4,3-b]indole-3(5H)-thiones and dimethyl acetylenedicarboxylate (DMAD) proceeds via two competing cascade pathways. Initially, both the pathways begin from thiocarbonyl sulfur and acetylene carbon atoms interaction. Then two parallel processes take place: an alkyne-thiocarbonyl metathesis and a (3 + 2) cycloaddition. In the next stages, in both cases, thiophene ring formation and thiopyran ring opening proceed. Finally, (4 + 2) cycloaddition reactions of intermediate thioketones and a second equivalent of DMAD leads to the resulting thiopyrano[4,3-b]indole derivatives bearing thienyl substituent. The kinetic and thermodynamic characteristics of both pathways were compared on the basis of DFT and ab initio 6-311++G(d,p) quantum chemical calculations.

Such CH acids as malononitrile, acetonitrile, and others were shown to be effective modifiers of the berberine skeleton at the C-8 position. Using the example of malononitrile, dimethylbarbituric acid, and Meldrum's acid, it was found that vinyl ethyl ethers obtained by the reaction of the CH acids and triethyl orthoformate can act as modifiers of the C-13 position. In an alkaline medium, using acetonitrile and malononitrile, both 8-substituted dihydroberberines with an sp3 hybridized C-8 carbon atom and dihydroberberines with an exocyclic double bond at the same atom can be obtained. It was determined that the stability of 13-substituted dihydroberberines depends on the nature of the substituents at the C-8 position and in the vinyl moiety at the C-13 atom. According to molecular docking data, the obtained 8-substituted dihydroberberines with an exocyclic double bond and 13-substituted dihydroberberines are promising for further evaluation in the systemic therapy of oncological diseases.

In modern chemical and biochemical studies, special attention is paid to molecular systems capable of generating nitric oxide (NO), which is one of the most important signalling molecules in the body and can trigger a whole cascade of reactions. Despite the importance of this molecule, the mechanisms of its formation in living organisms remain a subject of debate. This review combines the most important methods of releasing NO from endogenous and exogenous sources. The history of endogenous NO donors dates back more than 150 years, since the synthesis of nitroglycerin, which remains the standard vasodilator today, even though it is known that it and many other similar compounds lead to the development of a nitrate tolerance. Particular awareness is devoted to the mechanisms of NO formation without the participation of enzymes, since these methods are most important for creating exogenous sources of NO as drugs. The study of NO formation methods is centred on both the creation of new NO donors and understanding the mechanisms of tolerance to them.

The possibility of obtaining electroneutral substituted 13-vinylberberines was demonstrated experimentally and via quantum-chemical DFT/B3LYP calculations in the 6-31++G(d,p) basis set. The introduction of pharmacophoric fragments conjugated through vinyl moiety opened new possibilities for structural modification of berberine, enabling pronounced changes in tropicity toward supramolecular biological structures. The newly synthesized 13-vinylberberines were stable in their reduced form due to significant intramolecular electron density transfer from berberine ring system to the vinyl moiety bearing electron-withdrawing groups. It was demonstrated that berberine derivatives may exist not only in ion pair form consisting of organic cation and inorganic anion, but also as zwitterionic structures featuring significant intramolecular charge transfer. The obtained 13-vinylberberines exhibited biological activity against the highly pathogenic Vibrio cholerae.

In the present review, numerous experimental and theoretical data describing the properties of non-canonical DNA structures (NSs) are analyzed. NSs (G-quadruplex, i-motif, hairpin, and triplex) play an important role in epigenetic processes (including the genetic variability of viruses), are prone to energetically low-cost conformational transformations and can very effectively be used in the design of nanoscale devices. Numerous experimental data have been analyzed in connection with the so-called oligonucleotides-transformers (nucleotide sequences that able to fold not only into one, but also into several NSs). These sequences were recently predicted by our calculations using automata and graph theories ("Dafna" algorithm). Possible applications of the oligonucleotides-transformers in nanoengineering and genetic editing of organisms are considered.

The cascade reaction of thiopyrano[4,3-b]indole-3(5H)-thiones and dimethyl acetylenedicarboxylate (DMAD) was found. The mechanism has been investigated in detail by DFT PCM/B3LYP/6–311++G(d,p) quantum chemical calculations. Initially, the reaction occurs via an alkyne–thiocarbonyl metathesis mechanism. At the next stages, unprecedented rearrangement takes place: thiopyrane ring opening and thiophene ring closure proceed. Cycloaddition of intermediate thioketone and a second equivalent of DMAD leads to the resulting thiopyrano[4,3-b]indole derivative bearing thienyl substituent.

The possibility of obtaining electroneutral 8-amido derivatives of dihydroberberines was shown experimentally and with the support of quantum-chemical calculations based on the density functional theory (B3LYP/6-311+G(d,p)). In alkaline media, amides deprotonated to form amide anions, which, in turn, could add to the berberine framework at the C-8 position. Competing processes in this case were the reactions of the formation of 8-hydroxy- or 8-alkoxyberberines.

The possibility of obtaining electroneutral 8-substituted berberines was demonstrated experimentally as well as by DFT/B3LYP and ab initio MP2/HF quantum-chemical calculations with the 6-311+G(d,p) basis set. In alkaline media, it is possible to substitute the C-8 position of berberine with such C-nucleophiles as methyl ketones, acetic acid esters, nitriles, geminal di- and trihaloalkanes. This process proceeds stepwise. First, berberine is attacked by a hydroxide anion to form a covalently bonded 8-hydroxyberberine, then 8-hydroxyberberine reacts with a nucleophile in the nonionized (molecular) form.