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The alternative way of synthesis of valuable 5-amino-3-methylisothiazole and 3-methyl-4-nitroisothiazole has been presented and described. It appeared that new, undescribed 3,3′-dimethyl-4,4′-dinitro-5,5′-bisisothiazole has been produced as a side-product during synthesis. Both experimental and calculated spectral and electronic properties of 3-methyl-4-nitroisothiazole have been extensively researched and discussed. The complete vibrational assignments were made on the basis of potential energy distributions PED. The fully anharmonic infrared and Raman spectra with calculated anharmonic intensities for fundamental bands, overtones as well as combination bands are presented. Vibrational spectra predicted by anharmonic approximation agree very well with experimental data. The stability of molecules of 3-methyl-4-nitroisothiazole arising from hyper conjugative interaction has been estimated using natural bond orbital (NBO 6.0) analysis. The combined frontier molecular orbital and NBO analysis of canonical molecular orbitals was used to predict the most probable sites of 3-methyl-4-nitroisothiazole molecule where single electron can be accepted to and detached from. Measured reduction potential of 3-methyl-4-nitroisothiazole and calculated electron affinity point out that this compound is susceptible to reduction at the similar level of 1-methyl-3-nitropyrazole and this susceptibility is much more than respective 1-methyl-4-nitropyrazole. UV-Vis spectra analysis reveals a nature of valence electron excitation and electron transition of 3-methyl-4-nitroisothiazole. Besides, unambiguous assignment of NMR signal shifts of carbon atoms of isothiazole ring of 3-methyl-4-nitroisothiazole, 5-amino-3-methylisothiazole and intermediate and side products of synthesis was conducted thanks to full detailed analysis of 1H, 13C NMR spectra and their two dimensional (2D) variants. Additionally, molar enthalpy of vaporization (ΔHvap) of 3-methyl-4-nitroisothiazole has been estimated (ΔHvap = 52.2 kJ/mol).

Here, the Conductor-like Polarizable Continuum Model (CPCM) was used as a less demanding substitute of Periodic Boundary Conditions (PBC) method to attempt to reliably simulate infrared spectra and some structural parameters of solid compound - 5-amino-3-methyl-4-isoxazolecarbohydrazide (HIX). The measured relative electric permittivity of HIX was used as a simplified equivalent of electric intensity generating by other molecules of 5-amino-3-methyl-4-isoxazolecarbohydrazide in crystal structure. The application of CPCM has resulted in better conformity of calculated molecular parameters with experimentally found. Theoretical geometry was compared with data obtained with X-ray crystallography. Comparison of harmonic approximation with anharmonic one, based on the six selected characteristic vibrations, shows that non-scaled harmonic wavenumbers, calculated with CPCM, well correspond to experimental spectra. Additionally, the results point out that anharmonic approximation appeared to be strong sensitive for input geometry and calculation parameters used, so the results are sometimes unreliable, especially for low wavenumbers. Also, the new feasible ways of the synthesis of the titled compound is presented, one of which is particularly easy and highly efficient.

Regulatory neuropeptides control and regulate breathing in physiological and pathophysiological conditions. While they have been identified in the neurons of major respiratory areas, they can be active not only at the central level, but also at the periphery via chemoreceptors, vagal afferents, or locally within lungs and airways. Some neuropeptides, such as leptin or substance P, are respiratory stimulants; others, such as neurotensin, produce variable effects on respiration depending on the site of application. Some neuropeptides have been implicated in pathological states, such as obstructive sleep apnea or asthma. This article provides a concise review of the possible role and functions of several selected neuropeptides in the process of breathing in health and disease and in lung pathologies.

AWL3106 composed of opioid (dermorphin) and tachykinin (substance P7-11) pharmacophores is a new compound with high analgesic potency and markedly reduced ability to induce tolerance and dependence. The present study aimed to determine the respiratory and cardiovascular responses evoked by this peptide in urethane-chloralose anaesthetized, spontaneously breathing rats in the presence or absence of vagal connection. Intravenous injection of AWL3106 at a dose of 0.3μmol/kg in intact rats resulted in apnoea lasting 5.1 ± 0.7s. Breathing that followed was of diminished frequency (F) and augmented tidal volume (VT) with no significant impact on minute ventilation. AWL3106-challenge induced biphasic fall in arterial blood pressure with no effect on heart rate. Midcervical and supranodosal sectioning the vagal nerves prevented the occurrence of the apnoea and abrogated the post-AWL3106 reduction in F but failed to eliminate the increase in VT. Hypotensive response appeared to be less profound following supranodose vagotomy. NaloxoneHCl abolished solely the occurrence of apnoea. However additional blockade of tachykinin NK1 receptors with SR140333 was required to abolish VT increase, deceleration of breathing and to markedly suppress AWL3106-induced hypotension. The present study shows that extravagally controlled stimulation of VT maintains fairly regular ventilation by levelling the bradypnoeic effects. Although the peptide showed no cardiac effects, hypotension occurring beyond the vagal loop may limit future therapeutic benefits of this chimeric compound.

Aim Chimeric compound – PK20 despite its therapeutic activity on nociceptive and inflammatory processes may affect respiration and blood pressure. Our objective was to evaluate influence of the hybrid composed of endomorphin-2 and neurotensin fragments on ventilation, heart rate and blood pressure in anesthetized and awake rats. Methods The effects of PK20 (1 mg/kg) were studied either after its intravenous administration in anesthetized rats or intraperitoneal injection in awake state. Tidal volume and the timing components of the breathing pattern, arterial blood pressure, and heart rate were recorded. Results Intravenous administration of PK20 in the neurally intact rats evoked a dose-dependent apnoea followed by a transient insignificant increase in tidal volume and breathing rate. The blood pressure changes were biphasic: transient increase was replaced by prolonged hypotension. Midcervical vagotomy abrogated all post-PK20 respiratory effects. Hypotension was eliminated after blockade of neurotensin NTS 1 receptor, while respiratory changes were reduced by blockade of both: NTS 1 and μ opioid receptors. After PK20 intraperitoneal injection awake rats did not show any significant changes in ventilation and blood pressure. Conclusion This chimeric peptide should be used with care via intravenous administration in anesthetized animals since PK20 may evoke respiratory apnoea and hypotension. Nevertheless, applied intraperitoneally in the same dose in conscious rats induced no adverse effects.

Experiments were performed in anaesthetized, spontaneously breathing rats to: (1) analyse the respiratory and cardiovascular effects of C-terminal fragment of substance P (AWL2077) as referred to those exerted by the parent undecapeptide, (2) determine the involvement of lung vagal afferents to these responses. Each peptide was injected intravenously at a dose of 0.3μmol/kg into neurally intact or midcervically vagotomized rats. Administration of both compounds decreased tidal volume, minute ventilation, mean arterial blood pressure and heart rate, showing stimulatory (SP) and depressive (AWL2077) effects on the rate of breathing. Midcervical vagotomy reversed (post-SP) and precluded (post-AWL2077) respiratory rate responses and eliminated bradycardia evoked by both peptides. These findings indicate that the examined C-terminal pentapeptide was convergent with, but less potent than substance P in central depression of tidal volume and displayed divergence in the peripheral effect on respiratory timing.

The structural, vibrational, natural bond orbital and quantum chemical analysis of 5-amino-N’-[(E)-(2,4-dichlorophenyl)methylidene]-3-methyl-1,2-oxazole-4-carbohydrazide P7 and 5-[(E)-(2,4-dichlorobenzylidene)amino]-3-methyl[1,2]oxazolo[5,4-d]pyrimidin-4(5H)-one PQ7 have been calculated by using DFT/B3LYP method with 6–311++G(df,pd) basis set. The obtained results show that the calculated vibrational frequencies are in a good agreement with IR and Raman spectra. Characteristic bands in the IR spectra and Raman one were assigned. The flattening of the amino group, the shortening of the N-N bond and the increase of the C O bond length, in both reaction products relative to the substrate, have been described in detail. Final product PQ7 is more stable and harder than intermediate P7. Both compounds exhibit antimycobacterial activity against Mycobacterium fortuitum (MIC respectively 16 and 62.5 μg/mL) what together with the low toxicity profile makes them promising candidates for a further development as a new class of antimycobacterial compounds.

PK20M (Dmt-D-Lys-Phe-Phe-OH) is a novel modified endomorphin-2 (EM-2) peptide producing strong dose- and time-dependent antinociceptive activity. Yet its prototype, endogenous EM-2, has been reported to trigger respiratory and vascular effects such as apnea and hypotension. The purpose of this study was to investigate the potency of the PK20M to evoke respiratory and cardiovascular responses in comparison to endogenous endomorphins. The engagement of the vagal pathway and μ opioid receptors in mediation of these responses was investigated. The effects of intravenous injections of PK20M, EM-1, and EM-2 were studied in anaesthetized, spontaneously breathing rats. The main dose-dependent effect of all endomorphins in the intact rats was immediate apnea, blood pressure and heart rate decrease. PK20M produced apnea in at least half of the intact animals in a much smaller dose than EM-1 and EM-2. The effects of all compounds were abrogated by pre-treatment with MNLX, a peripherally acting μ receptor antagonist. Cervical vagotomy eliminated arrest of breathing in the case of each tested compound. Hypotension was reduced by vagi section only after EM-1 and EM-2 administration. Our results demonstrated that apnea and bradycardia caused by systemic injection of all endomorphins were mediated via activation of μ vagal opioid receptors. The hypotension depended on intact vagi nerves only in the case of EM-1 and EM-2, whereas PK20M decreased blood pressure via other mechanisms outside vagal innervation. Modified opioid agonist is more potent in evoking extended hypotension; at the same time, it produces an arrest of breathing less frequently than its prototype EM-2.

Both experimental and calculated spectral and electronic properties of two isomers 1-methyl-3-nitropyrazole and 1-methyl-5-nitropyrazole have been demonstrated and discussed in details based on normal mode analysis. The fully anharmonic infrared spectra with calculated anharmonic intensities for fundamental bands, overtones and combination bands were also reported. The stability of title molecules arising from hyper conjugative interaction have been demonstrated using natural bond orbital (NBO) analysis. Electron affinities clearly point that 1-methyl-5-nitropyrazole should be much more susceptible to reduction process than 1-methyl-3-nitropyrazole what has been experimentally confirmed by measurement of reduction potential. For 1-methyl-5-nitropyrazole, unambiguous assignment of values of proton and carbon chemical shifts to appropriate protons and carbons has been made thanks to full analysis of 1 H and 13 C NMR spectra and two dimensional (2D) 1 H 1 H and 1 H 13 C NMR COSY spectroscopy.

Both experimental and calculated spectral and electronic properties of 1-methyl-4-nitropyrazole have been demonstrated. Experimental values have been compared with theoretical computations and also new hybrid density functionals, APF (Austin–Petersson–Frisch) and APF(D), have been tested and compared to B3LYP hybrid functional. The theoretical wavenumbers of fully anharmonic infrared and Raman spectra with anharmonic intensities of 1-methyl-4-nitropyrazole are in very good agreement with the experimental observations. The detailed interpretation of the infrared and Raman spectra is reported based on potential energy distribution (PED). The ring N1 N2 bond distance of 1-methyl-4-nitropyrazole, calculated with both APF/6-311++G( df , pd ) and APF-D/6-311++G( df , pd ) models, is much underestimated in comparison with X-ray experimental value. Overall results point that B3LYP functional with 6-311++G( df , pd ) basis function better predicts the bond lengths and angles of titled compound than both APF and APF-D ones. As a key factor for biological activity of nitro compounds, the redox potential of 1-methyl-4-nitropyrazole in water solution was also measured and then was set against the calculated electronic properties. The analysis of the calculated components of HOMO and LUMO orbitals has shown that nitrogen and oxygen atoms of nitro group are the most probable site of acceptance of electron. Hence, nitro group should be the most sensitive fragment of 1-methyl-4-nitropyrazole molecule to the reduction process. Moreover, the stability of the 1-methyl-4-nitropyrazole arising from hyper conjugative interactions has been studied using natural bond orbital (NBO) analysis. Unambiguous assignment of values of proton chemical shifts to appropriate protons has been finally made thanks to two dimensional (2D) 1 H– 1 H NMR spectroscopy.

Both spectral and structural studies of 5-amino-3-methyl-4-isoxazolecarbohydrazide (HIX) were done and compared to calculated parameters using ab initio DFT methods. A detailed interpretation of the infrared and Raman spectra of title molecule is reported on the basis of the calculated potential energy distribution (PED). The conformational search for possible conformers and tautomers of title compound has been conducted and widely discussed. N-deuterated isotopologue of 5-amino-3-methyl-4-isoxazolecarbohydrazide (HIXD) was synthesized to eliminate disturbing frequencies in carbonyl region of IR and Raman. Besides, N-deutaration enabled the unambiguous assignment some bands to specific vibrations. Moreover, the stability of the 5-amino-3-methyl-4-isoxazolecarbohydrazide arising from hyper conjugative interactions has been studied using natural bond orbital (NBO) analysis.

2,3,4,5,6-Pentafluoroaniline (PFA) is a very attractive object to theoretical study of fluorine interaction with an aromatic ring. Two major opposite effects are observed in PFA: interaction of the σ–π electron donating amino group, promoting electrophilic substitution at the ortho/para position by increasing the electron density at the ortho/para carbons versus fluorine substituents. This very strongly withdraws electron density from the aromatic system through the σ bond (inductive effect) and donates electron density through the π system (resonance effect). The stability of PFA arising from hyper conjugative interaction is investigated with natural bond orbital (NBO) analysis. The influences of the fluorine atoms on the geometrical and electronic properties as well as the detailed interpretation of vibrational spectra and potential energy distribution (PED) are also reported. The assignment of fundamental frequencies is confirmed by the qualitative agreement between the observed and calculated wavenumbers.

In this paper, we report a strategy for preparing an inorganic zinc titanate precursor by applying a chemical bath deposition method (CBD) to ZnO nanocrystals in an aqueous layered titanate colloid. The zinc titanate precursor, obtained as a precipitate, undergoes profound changes under the influence of elevated temperatures in normal atmospheric conditions and allows us to obtain zinc titanate ZnTiO3 with a rhombohedral symmetry. Investigations of its dielectric properties enabled us to determine a dielectric permittivity (ɛ) of 25, a low loss factor tan(δ)

In this paper, dielectric spectroscopy investigations of organic–inorganic hybrid composite obtained from (2-hydroxypropyl)cellulose (HPC) with nanosheet crystallites of quasi-TiO2 are presented. This hybrid belongs to the class of composites, which have no covalent bonds between organic and inorganic constituents and the behaviour of composite is determined mainly by interface of two constituents. The analysis of the molecular dynamics of the hybrid system reveals the influence of the nanosheet crystallites of quasi-TiO2 on the relaxation processes of HPC matrix. The relaxation strength of γ process strongly increases in composite as compared to neat HPC. A shift to higher temperature has been evidenced in the case of α and β processes. A higher value of the slope of the maximum frequency vs. the inverse temperature for the α-relaxation of the composite has been observed. At high temperatures the mesomorphic behaviour of HPC has been drastically reduced in the composite. The results of our investigations are interpreted in terms of a presence of intermolecular forces between HPC and nanosheet crystallites of quasi-TiO2.

Our results in the field of adopting the chemical bath deposition method (CBD) for the deposition of the nanostructures of copper compounds are presented in this work. The deposition of copper compounds by means of the CBD method was carried out at the water solution of copper nitrate (acetate) salts and hexamethylenetetramine. There are two distinct periods in the deposition of copper compounds in the same bath. At the shorter deposition time the good quality nanocrystals of the copper hydroxy nitrate (acetate) salts with a different morphology are obtained. Decomposition of the copper salts to the CuO in the water bath can be observed after several hours of the copper hydroxy salts deposition. The SEM images and the XRD patterns of the CuO layer, which was produced by decomposition of copper hydroxy salts by the CBD method, show a morphology and texture different from the CuO layer prepared by thermal decomposition of the deposited copper hydroxy salts at an elevated temperature. It has been suggested that the main force in decomposition of copper hydroxy salts to CuO in the course of CBD process may be related with a strain, which exists between the CuO nanoparticles on the modified glass substrate and the deposited copper hydroxy salt. The decomposition reaction of copper hydroxy salts in the solid phase may be accelerated by a strain. The influence of the strain on the morphology of CuO nanostructures is demonstrated on the basis of the basic copper nitrate salt hybridised with titanate nanosheets.

In this paper, we have prepared new type of organic–inorganic hybrid materials based on covalent bond between the two constituents: elastomer and titanium oxocluster. Commercial hydrogenated acrylonitrile-butadiene rubber (HNBR)-Therban ® 3407 was selected as the matrix for mixing the titanium oxocluster. Three different samples containing the elastomer and peroxide, elastomer, peroxide and titanate, and elastomer and titanate, respectively were prepared. The dielectric permittivity have been scanned over a wide range of frequencies and temperatures in order to determine the how the titanate and the peroxide influences the molecular mobility. Complementary DSC and mechanical analysis were performed. We found that the presence of titanates-compounds strongly influences the mobility of the ions and it’s reflected in the low activation energy for the ionic conductivity. In spite that the glass transition temperature is held constant, the temperature dependence of the α process, as well as the free volume at the glass transition, the fragility parameter and the ΔCp during the glass transition are strongly influenced by the composition.

The respiratory effects of stimulation of mu-opioid receptors were studied in spontaneously breathing anaesthetized rats that were either neurally intact or subjected to bilateral supranodosal vagotomy. An intravenous dermorphin bolus of 0.5 mg/kg evoked the apnea followed by breathing of reduced rate and compensatory augmentation of tidal volume, which resulted in an invariable minute ventilation. Cardiovascular effects consisted of hypotension and temporary fall in heart rate. In rats initially treated by supranodosal vagotomy, dermorphin did not evoke any respiratory and cardiovascular effects. These results indicate that vagal pathway and the nodose ganglia are involved in dermorphin-induced respiratory depression.

In 1999–2002, 79 patients were treated operatively due to ankles fractures. In nine patients (11.4%) internal osteosynthesis by minimal surgical approach was applied. Post-operative treatment involved plaster splint immobilisation for 8–12 weeks. In the post-operative result evaluation, the AOFAS 100-point grading scale was applied. Normal union was achieved after 12 weeks of treatment, good functional results after 20 weeks. No soft tissues, cutaneous or union complications were observed. In the scale, the operated patients obtained from 71 to 96 points. Conclusions : 1.Poor condition of soft tissues surrounding the area of ankles fracture, thus impeding the healing of wounds, is an indication for internal osteosynthesis by minimal surgical approach. 2.Internal osteosynthesis by minimal surgical approach is an effective method of ankles fracture treatment.

The ortho-meta-, and para-fluoro substituted anilines are prototype molecules for investigation of the interactions of both the amino group and the fluorine atom with the aromatic ring. The molecular structures, natural atomic charges and theoretical anharmonic Raman and infrared spectra of the three fluoroaniline isomers have been calculated by using the density functional B3LYP method with the extended 6-311++G(df,pd) basis set. The Raman and infrared spectra of 2FA, 3FA, and 4FA have been recorded. The detailed vibrational assignments of the experimental spectra have been made on the basis of the calculated potential energy distributions, PEDs. The effect of fluorine substituent on the aniline ring geometry and charge distribution, the nature of the characteristic “marker bands” and a quenching of intensities of some bands are discussed. It is shown that the frequencies of the NH2 stretching vibrations depend on the degree of pyramidalization of the C–NH2 group, in the isomers. In 2FA and 3FA, the NH2 stretching frequencies are higher than those in 4FA. This corresponds to a more flattened structure of the amino group in 2FA and 3FA, in comparison to 4FA.