ENDOGENOUS INTOXICATION SYNDROME ACTIVITY IN BILIARY AUTONOMIC VISCERO-VISCERAL CARDIONEUROPATHY

Toxic excess of biologically active substances named middle molecules (MM), which include byproducts of normal and altered metabolism, products of inflammation and oxidation, bacterial remnants, antibodies and immunoactive substances, plays an important role in pathogenesis of gallbladder diseases and biliary autonomous viscero-visceral cardioneuropathy (BAVVCNP). In order to assess activity of the endogenous intoxication syndrome secondary to BAVVCNP, we examined 20 patients with coronary heart disease to determine the levels of MM in the blood (total and at 238, 254, 266, and 280 nm waves); the levels of MM in urine (at 238, 254, 266, 282, 288, and 310 nm waves) with calculation of aromaticity index (MM 238/280), peptide-nucleotide index (MM 238/266), distribution index (MM 280/254), and L-arginine, and nitrites of the urine. The results were statistically processed. It was revealed that in case of BAVVCNP the severity of the endogenous intoxication syndrome was higher for all specific parameters of endotoxicosis, and especially for the total level of MM in blood (0.77 ± 0.13 units vs. 0.46 ± 0.13 units, p = 0.08), the MM level at 238 nm wave (1.53 ± 0.55 vs. 0.49 ± 0.06, p = 0.08) and hydrophilic MM level in the urine at 288 nm long waves (0.72 ± 0.12 vs. 0.40 ± 0.11, p = 0.05) and 310 nm (0.27 ± 0.08 vs. 0.10 ± 0.03, p <0.05). According to the literature, this may indicate an increase in levels of cholecystokinin, leptin, endothelin, proinflammatory interleukins and tumor necrosis factor α. According to the correlation analysis, activation of endogenous intoxication syndrome was associated with lipid distress syndrome, increased leptin content and accelerated renal filtration.

Can Aromaticity of Fused Aromatic Ring in 1,3-Pentadiene Modulate its Reactivity towards [1,5]-Halo Shift? - A DFT Study

In (Z)-1,3-pentadienes, [1,5]-H migration is suprafacially allowed while fluorine shift in this system takes place by a Contra Hoffmann antarafacial pathway for which aromaticity is the driving force. If aromaticity of the transition structure (TS) can drive a reaction towards a disallowed pathway as found in the case of fluorine, the role of aromatic ring annealed to (Z)-1,3-pentadienes in determining the reaction pathway and barrier is worth noting. Hence, the combined role of aromaticity of transition state and the loss in aromaticity of the annealed ring has been explored during the [1,5]-X (X = H, F, Cl, Br) shifts in aromatic (benzene/naphthalene) annealed 1,3-pentadiene system. Notable correlations between various aromaticity index NICS(0,1) with activation barriers show that aromaticity of transition structure in pericyclic reaction can drive the stereochemical course of a reaction. The distinct effect of fluorine to other halogens is the antara migration while the other halogens (Cl & Br) prefer supramode.

Application of the Extended HOMED (Harmonic Oscillator Model of Aromaticity) Index to Simple and Tautomeric Five-Membered Heteroaromatic Cycles with C, N, O, P, and S Atoms

The geometry-based HOMA (Harmonic Oscillator Model of Aromaticity) descriptor, based on the reference compounds of different delocalizations of n- and π-electrons, can be applied to molecules possessing analogous bonds, e.g., only CC, only CN, only CO, etc. For compounds with different heteroatoms and a different number of CC, CX, XX, and XY bonds, its application leads to some discrepancies. For this reason, the structural descriptor was modified and the HOMED (Harmonic Oscillator Model of Electron Delocalization) index defined. In 2010, the HOMED index was parameterized for compounds with C, N and O atoms. For parametrization, the reference molecules of similar delocalizations of n- and π-electrons were employed. In this paper, the HOMED index was extended to compounds containing the CP, CS, NN, NP, PP, NO, NS, PO, and PS bonds. For geometrical optimization of all reference molecules and of all investigated heterocompounds, the same quantum–chemical method {B3LYP/6-311+G(d,p)} was used to eliminate errors of the HOMED estimation. For some tautomeric systems, the Gn methods were also employed to confirm tautomeric preferences. The extended HOMED index was applied to five-membered heterocycles, simple furan and thiophene, and their N and P derivatives as well as for tautomeric pyrrole and phosphole and their N and P derivatives. The effects of additional heteroatom(s) in the ring on the HOMED values for furan are parallel to those for thiophene. For pyrroles, aromaticity dictates the tautomeric preferences. An additional N atom in the ring only slightly affects the HOMED values for the favored and well delocalized NH tautomers. Significant changes take place for their rare CH forms. When intramolecular proton-transfer is considered for phosphole and its P derivatives, the PH tautomers seem to be favored only for 1,2,3-triphosphole/1,2,5-triphosphole and for 1,2,3,5-tetraphosphole. For other phospholes, the CH forms have smaller Gibbs energies than the PH isomers. For phosphazoles, the labile proton in the favored form is linked to the N atom. The PH forms have smaller HOMED indices than the NH tautomers but higher than the CH ones.

Preparation and molecular structures of N′-(2-heteroarylmethylidene)-3-(3-pyridyl)acrylohydrazides

The crystal and molecular structures of N′-(2-furylmethylidene)-3-(3-pyridyl)acrylohydrazide and N′-(2-thienylmethylidene)-3-(3-pyridyl)acrylohydrazide are reported, and the influence of the type of the heteroatom on the aromaticity of the aromatic rings is discussed. Both molecules are nearly planar. The geometry of the acrylohydrazide arrangement is comparable to that of homologous compounds. Density functional theory (DFT) calculations were performed in order to analyze the changes in the geometry of the studied compounds in the crystalline state and for the isolated molecule. The most significant changes were observed in the values of the N–N and C–N bond lengths. The harmonic oscillator model of aromaticity index, calculated for the furan and thiophene rings, demonstrated a noticeable increase in aromaticity in comparison to isolated rings and their DFT-calculated structures. By contrast, the nucleus independent chemical shift index indicated a decrease in aromatic character of the rings containing heteroatoms.

A study on the aromaticity and ring currents of dithienopyridines and dithienobenzene

The global aromaticity of dithienopyridine and dithienobenzene isomers was investigated using the topological resonance energy (TRE) and percentage topological resonance energy (%TRE) methods. The effect of variations in the positions of sulfur and nitrogen atoms on [Formula: see text]-electron delocalization is analyzed. The local aromaticity of these isomers is described based on the bond resonance energy (BRE) and circuit resonance energy (CRE) methods. Our BRE and CRE results show that structure of the central six-membered rings has a strong effect on global aromaticity. The aromaticity of these dithienopyridine isomers is enhanced when a complete pyridine unit exists in their middle ring structure, while the aromaticity of the dithienobenzene isomers is enhanced when a complete benzene unit exists in their middle ring structure. For dithienopyridines, our results obtained using the TRE method correlate well with the Bird aromaticity index as reported in the literature. Our ring-current results show that all these compounds are diatropic systems.

On splitting of the NICS(1) magnetic aromaticity index

The NICS(1) magnetic aromaticity index is split into NICS(1) and NICS(−1) indices when the points 1 Å above and below the ring center are inequivalent by symmetry. The two indices characterize the aromaticity of the two ring faces rather than the ring itself.

An electronic aromaticity index for large rings

We introduce a new electronic aromaticity index, AV1245, consisting of an average of the 4-center indices along the ring that keep a positional relationship of 1, 2, 4, 5.