In recent years, a number of synthetic potentiators of antibiotics have been discovered. Their action can significantly enhance the antibacterial effect and limit the spread of antibiotic resistance through inhibition of bacterial cystathionine-γ-lyase. To expand the known set of potentiators, we developed methods for the synthesis of five new representatives of 6-bromoindole derivatives—potential inhibitors of bacterial cystathionine-γ-lyase—namely potassium 3-amino-5-((6-bromoindolyl)methyl)thiophene-2-carboxylate (MNS2) and its 6-bromoindazole analogs (MNS3 and MNS4), along with two 6-broindazole analogs of the parent compound NL2. Their syntheses are based on 6-bromoindole, 6-bromoindazole and methyl 5-(bromomethyl)-3-((ethoxycarbonyl)amino)thiophene-2-carboxylate as the main building blocks, assembling the rest of the heterocyclic system on their basis at the nitrogen atom. We assessed the ability of the new inhibitors to potentiate the antimicrobial activity of gentamicin.

Unstable tetra(methoxycarbonyl)cyclopentadienone was investigated in the synthesis of electron-deficient cycloheptatrienes via [4+2]-cycloaddition/cycloelimination reaction with cyclopropenes. The use of its stable dimer did not afford the product although similar reactions with alkynes have been reported. Quantum chemical calculation revealed that cyclopentadienone is not generated from the dimer and the reaction with alkynes proceeds via a more complicated cycloelimination/cycloaddition/cycloelimination cascade. However, the formation of cycloheptatrienes was found favorable over the formation of the dimer. Therefore, the trapping of tetra(methoxycarbonyl)cyclopentadienone upon formation was successful to give cycloheptatrienes with five ester groups. The use of methyl coumalate as a four-electron component was successful with cyclopropenes containing only one ester group to afford only two ester groups in the product.

Antiaromatic nucleophilic substitution reactions in cycloheptatrienide pyridinium and phosphonium zwitterions with initial formation of a cycloheptatetraene intermediate are explored. The mechanism was supported by quantum chemical calculations, first-order reaction kinetics, and high-resolution mass spectrometry. The pyridinium zwitterion exhibited weak antiaromaticity, whereas the intermediate displayed Möbius aromaticity, as evidenced by nuclear independent chemical shift values and the shape of its HOMO. This study represents the eighth confirmed instance of a Möbius-aromatic organic species in its ground state.

Cystathionine-γ-lyase (CSE) is a key enzyme for H2S generation in the pathogenic bacteria Staphylococcus aureus, Pseudomonas aeruginosa, etc. Suppression of CSE activity significantly increases the antibiotic susceptibility of bacteria. In this work a method to synthesize a novel indole-based CSE inhibitor, 3-ammo-5-[(6-bromo-1H-indol-1-yl)methyl]thiophene, named MNS1, has been developed. The synthesis of MNS1 is based on the modification of substituted thiophene as a main structural fragment, which is involved in alkylation of 6-bromoindole at final steps. The dissociation constant of the MNS1 complex with S. aureus CSE (SaCSE) is 0.5 μM, one order of magnitude lower than with human CSE (hCSE). MNS1 was shown to efficiently enhance the antibacterial effect of gentamicin against Bacillus subtilis, suggesting its possible use as an antibiotic potentiator to inhibit the growth of CSE-expressing bacterial cells.

Investigations of the nature and degree of antiaromaticity of cycloheptatrienyl anion derivatives using both experimental and computational tools are presented. The ground state of cycloheptatrienyl anion in the gas phase is triplet, planar and Baird-aromatic. In DMSO, it assumes a singlet distorted allylic form with a paratropic ring current. The other derivatives in both phases assume either allylic or diallylic conformations depending on the substituent pattern. A combination of experimental and computational methods was used to determine the pKa values of 16 derivatives in DMSO, which ranged from 36 to -10.7. We revealed that the stronger stabilization of the anionic system, which correlates with acidity, does not necessarily imply a lower degree of antiaromaticity in terms of magnetic properties. Conversely, the substitution pattern first affects the geometry of the ring through the bulkiness of the substituents and their better conjugation with a more distorted system. Consequently, the distortion reduces the cyclic conjugation in the pi-system and thereby decreases the paratropic current in a magnetic field, which manifests itself as a decrease in the NICS. The triplet-state geometries and magnetic properties are nearly independent on the substitution pattern, which is typical for simple aromatic systems. Cycloheptatrienyl anions are studied in terms of their acidity, structure, and antiaromatic properties. The substituents directly affect the acidity of the anion, while the magnetic properties originate from the geometry of the anion, which in turn is determined by the conjugation and steric properties of the substituents. image

The study investigated the reactivity of various CH-acids/conjugated bases in the synthesis of hepta(methoxycarbonyl)cycloheptatriene through a cascade reaction. NMR spectral monitoring identified (methoxycarbonyl)methylpyridinium as the true nucleophilic component in the original synthesis based on methyl diazoacetate. The scope of CH-acids capable of participating in the reaction was expanded to include sulfonium salts and sulfones, whereas certain nucleophiles were found to be ineffective. A correlation between the pKa values of CH-acids and the formation of seven-membered rings in the cascade reaction was established.

An approach to the synthesis of seven-membered systems via the chain elongation of nucleophilic propenes and subsequent 8π-electrocyclization is proposed. The cascade reaction yields either cycloheptadienes or bicycloheptenes, and the latter are formed via a 6π-electrocyclization of intermediate cycloheptadienyl anion which was proved to be reversible in a basic medium. The electrocyclic nature of the ring-closing reactions was supported by density functional theory and DLPNO/CCSD(T) calculations. Highly electron-deficient cycloheptatrienes can be obtained from cycloheptadienes or bicycloheptenes via oxidation either introduced into the cascade reaction or performed as a separate reaction, with the overall yield of up to 81%. The oxidation step was performed by means of a rarely encountered Cu(II)-catalyzed dehydrogenation of cycloheptadienes or bicycloheptenes, and so the reaction mechanism was proposed. Stable formally 8π-antiaromatic cycloheptatrienyl-anion containing compounds were obtained, and some correlations between their UV-vis spectra and the structure of the distorted cycloheptatrienyl-anion moiety were clarified. Additionally, a base-induced retro-[2 + 2]-cycloaddition in a bicycloheptene derivative gave cyanotetra(methoxycarbonyl)cyclopentadienyl cesium.

A novel fluorescent core based on electron-deficient 9-methoxypyrroloisoquinolinetrione moiety with a condensed imide cycle is developed. The new class of dyes show large Stokes shift up to 6519 cm-1 (Delta lambda up to 130 nm), however, unlike parent 5-hydroxyisoquinolones, 9-methoxypyrroloisoquinolinetrione are not superphotoacidic which could be responsible for the large Stokes shifts. At the same time methylation of 5-hydroxyisoquinolones reduces Stokes shift from 5086 to 4689 cm-1. The increase in Stokes shift upon the formation of an imide cycle was shown to be due to unusual bond-lengths relaxation involving the imide ring.

Four electron-deficient 5-hydroxyisoquinolones are among the strongest currently known superphotoacids with excited state pKa* down to −5.8 and ΔpKa up to 9.0, as estimated experimentally via Förster cycle and supported by quantum chemical calculations. A condensed teracyclic derivative is a weaker photoacid with ΔpKa of around three units. The superphotoacidity in turn initiates pH-switched Stokes shifts: irrespective of the form (protonated or deprotonated) absorbing the photon, only emission of the deprotonated form is observed in protic media.

A novel class of fluorescent electron-deficient 5-hydroxyisoquinolones is proposed. The new luminophores are obtained via the reaction of stable and easily available hepta(methoxycarbonyl)cycloheptatrienyl potassium with alkylamines, anilines and acylhydrazines. The new one-pot protocol is efficient with a large scope of primary amines. The solvolysis of N-acylamino substituted 5-hydroxyisoquinolones and subsequent reactions have provided a pathway to further functionalization. Nearly all compounds have demonstrated fluorescence with considerably large the Stokes shifts (up to 6169 cm(-1)) except for those containing a nitro group as well as O-substituted products. In most other cases neither quantum yield nor absorption and emission maxima nor the Stokes shifts substantially depended on the substituent at the isoquinolinone ring nitrogen atom.

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

The reaction of di(methoxycarbonyl)tetrazine with substituted cycloprop-2-ene-1-carboxylates gives a series of 3,4-diazanorcaradienes and 1,2-diazepines. The influence of the nature of cyclopropenes and the reaction conditions on its selectivity was investigated. The addition of nucleophiles to norcaradienes was studied and a rare example of the "walk" rearrangement in this class of compounds was revealed.

A new and simple procedure for the synthesis of heptamethyl cyclohepta-1,3,5-triene-1,2,3,4,5,6,7-heptacarboxylate in a 51% yield is presented. An optimization of the reaction conditions was performed, and a convenient protocol for the isolation of the reaction product was developed. The structure of the key electrophilic intermediate was determined by means of NMR spectroscopy, and a plausible reaction mechanism is proposed.

The mechanism for the reaction of dimethyl malonate with dimethyl acetylenedicarboxylate in the presence of pyridine and acetic acid to form isomeric octa(methoxycarbonyl)cycloheptadienes was established. The formation of intermediary N-[di(methoxycarbonyl)vinyl]pyridinium acetate was proven by means of NMR spectroscopy. On the basis of the established mechanism, dimethyl dibromosuccinate was proposed to be used instead of dimethyl acetylenedicarboxylate. A novel method for the synthesis of penta(methoxycarbonyl)cyclopentadienylsodium through the reduction of hepta(methoxycarbonyl)cycloheptatriene with sodium borohydride, electrocyclic ring contraction and retro-[2+2]-cycloaddition was developed.

Cycloheptatriene derivatives are studied by means of resonance electron capture negative ion mass spectrometry (REC NIMS). The average lifetimes of molecular negative ions (NIs) are measured with respect to electron autodetachment. Using the Arrhenius approach, electron affinity EAa of the molecules under study is estimated, and the effective temperature of the resulting negative molecular ions is determined as a function of the electron energy. It is assumed that the dissociation of negative molecular ions in the ground electronic state is a process similar to that of the thermal degradation of molecules.

A reaction of isopropyl- ortho -carborane with n -butyllithium, followed by treatment of the lithium derivative formed with boron trichloride, chlorodimethoxyborane, or chloropinacolatoborane furnished C -boryl- ortho -carboranes 1a - c . Further functionalization of 1-Cl 2 B-2-Pr i -1,2-C 2 B 10 H 10 ( 1a ) with pentafluorophenylmagnesium bromide or pentafluorophenol led to 1-(C 6 F 5 ) 2 B-2-Pr i -1,2-C 2 B 10 H 10 ( 2 ) and (1-(C 6 F 5 O)B-2-Pr i -1,2-C 2 B 10 H 10 ) 2 O ( 3 ), respectively. A reaction of 1-(MeO) 2 B-2-Pr i -1,2-C 2 B 10 H 10 ( 1b ) with the complexes of BH 3 with THF and dimethyl sulfide gave rise to carboranylborane adducts 4a , b . The use of the complex of 1-H 2 B-2-Pr i -1,2-C 2 B 10 H 10 with dimethyl sulfide 4b as a hydroboration agent in the reactions with hex-1-ene and phenylacetylene allowed us to obtain dialkyl- and di(phenylolefin)-containing C -isopropyl- ortho -carboranylboranes, respectively. The reaction of C -isopropyl- ortho -carboranyldimethoxyborane with triallylborane led to the substitution of only one of two MeO groups with the allyl one, which is explained by the steric effects of bulky carboranyl substituent in the precursor. Compounds obtained are characterized by X-ray diffraction analysis.