Study of the Structure and Infrared Spectra of LiF, LiCl and LiBr Using Density Functional Theory (DFT).

The paper presents a study of the crystal structure of anhydrous halides LiF, LiCl and LiBr using density functional theory. Models composed of 125 atoms were used for this study. The theoretical values of the lattice parameters and the distribution of charges in the crystals were determined. Using the assumed models at the level of theory DFT/B3LYP/6-31+g*, the theoretical infrared spectra of lithium halides (LiF, LiCl and LiBr) were calculated for the first time. Additionally, measurements of experimental far-infrared (FIR) spectra were performed for these salts. All the obtained theoretical values were compared with experimental data obtained by us and those available in the literature.

Probing the stereochemical structure of carenes using Raman and Raman optical activity spectroscopy.

The great interest in terpene compounds such as 2-, 3- and 4-carene is due to their undeniable biological activity. However, in recent years, there has been increasing interest in carenes in the context of biofuels. The current growing and insatiable demand for petroleum fuels creates an area for alternative biofuels. Research shows that natural products, which contain compounds from the carenes family, such as pine oil or turpentine (3-carene can constitute up to 70% of the composition of turpentine), can be successfully used as biofuels or additives in biofuels. In this work, both experimental and calculated (DFT/B3LYP/aug-cc-pVDZ) Raman and ROA (Raman optical activity) spectra of 1S,3R-cis-4-carene and 1S,3S-trans-4-carene were reported and analyzed for the first time. Then these spectra were compared with Raman and ROA spectra of other chiral members of the carenes family (1S-2-carene and 1S-3-carene). This knowledge about the spectra of individual carenes made it possible to identify (+)-1S-3-carene in selected samples of pine essential oil from the needles of Pinius sylvestris (Scots pine).

HPLC-UV and GC-MS Methods for Determination of Chlorambucil and Valproic Acid in Plasma for Further Exploring a New Combined Therapy of Chronic Lymphocytic Leukemia.

High performance liquid chromatography with ultra-violet detection (HPLC-UV) and gas chromatography-mass spectrometry (GC-MS) methods were developed and validated for the determination of chlorambucil (CLB) and valproic acid (VPA) in plasma, as a part of experiments on their anticancer activity in chronic lymphocytic leukemia (CLL). CLB was extracted from 250 µL of plasma with methanol, using simple protein precipitation and filtration. Chromatography was carried out on a LiChrospher 100 RP-18 end-capped column using a mobile phase consisting of acetonitrile, water and formic acid, and detection at 258 nm. The lowest limit of detection LLOQ was found to be 0.075 µg/mL, showing sufficient sensitivity in relation to therapeutic concentrations of CLB in plasma. The accuracy was from 94.13% to 101.12%, while the intra- and inter-batch precision was ≤9.46%. For quantitation of VPA, a sensitive GC-MS method was developed involving simple pre-column esterification with methanol and extraction with hexane. Chromatography was achieved on an HP-5MSUI column and monitored by MS with an electron impact ionization and selective ion monitoring mode. Using 250 µL of plasma, the LLOQ was found to be 0.075 µg/mL. The accuracy was from 94.96% to 109.12%, while the intra- and inter-batch precision was ≤6.69%. Thus, both methods fulfilled the requirements of FDA guidelines for the determination of drugs in biological materials.

The Impact of Chlorambucil and Valproic Acid on Cell Viability, Apoptosis and Expression of p21, HDM2, BCL2 and MCL1 Genes in Chronic Lymphocytic Leukemia.

Malignant cells in chronic lymphocytic leukemia (CLL) show resistance to apoptosis, as well as to chemotherapy, which are related to deletions or mutations of TP53, high expression of MCL1 and BCL2 genes and other abnormalities. Thus, the main goal of the present study was to assess the impact of chlorambucil (CLB) combined with valproic acid (VPA), a known antiepileptic drug and histone deacetylation inhibitor, on apoptosis of the cells isolated from 17 patients with CLL. After incubation with CLB (17.5 µM) and VPA (0.5 mM), percentage of apoptosis, as well as expression of two TP53 target genes (p21 and HDM2) and two genes from Bcl-2 family (BCL2 and MCL1), were tested. As a result, an increased percentage of apoptosis was observed for CLL cells treated with CLB and VPA, and with CLB alone. Under the treatment with the drug combination, the expression of p21 gene was visibly higher than under the treatment with CLB alone. At the same time, the cultures under CLB treatment showed visibly higher expression of BCL2 than the cultures with VPA alone. Thus, the present study strongly suggests further investigations on the CLB and VPA combination in CLL treatment.

Anticonvulsant valproic acid and other short-chain fatty acids as novel anticancer therapeutics: Possibilities and challenges.

Results from numerous pre-clinical studies suggest that a well known anticonvulsant drug valproic acid (VPA) and other short-chain fatty acids (SCFAs) cause significant inhibition of cancer cell proliferation by modulating multiple signaling pathways. First of all, they act as histone deacetylase (HDAC) inhibitors (HDIs), being involved in the epigenetic regulation of gene expression. Afterward, VPA is shown to induce apoptosis and cell differentiation, as well as regulate Notch signaling. Moreover, it up-regulates the expression of certain G protein-coupled receptors (GPCRs), which are involved in various signaling pathways associated with cancer. As a consequence, some pre-clinical and clinical trials were carried out to estimate anticancer effectiveness of VPA, in monotherapy and in new drug combinations, while other SCFAs were tested in pre-clinical studies. The present manuscript summarizes the most important information from the literature about their potent anticancer activities to show some future perspectives related to epigenetic therapy.

Kinetics and Characterization of Degradation Products of Dihydralazine and Hydrochlorothiazide in Binary Mixture by HPLC-UV, LC-DAD and LC-MS Methods.

Dihydralazine and hydrochlorothiazide were stored at high temperature and humidity, under UV/Vis light and different pH, as individual drugs and the mixture. Then, a sensitive and selective HPLC-UV method was developed for simultaneous determination of dihydralazine and hydrochlorothiazide in presence of their degradation products. Finally, the degradation products were characterized through LC-DAD and LC-MS methods. Dihydralazine was sensitive to high temperature and humidity, UV/Vis light and pH ≥ 7. At the same time, it was resistant to acidic conditions. Hydrochlorothiazide was sensitive to high temperature and humidity, UV/Vis light and changes in pH. Its highest level of degradation was observed in 1 M HCl. Degradation of the drugs was higher when they were stressed in the mixture. In the case of dihydralazine, the percentage degradation was 5-15 times higher. What is more, dihydralazine became sensitive to acidic conditions. Hydrochlorothiazide was shown to be more sensitive to UV/Vis light and pH > 4. Degradation of dihydralazine and hydrochlorothiazide followed first-order kinetics. The quickest degradation of dihydralazine was found to be in 1 M NaOH while of hydrochlorothiazide was in 1 M HCl (individual hydrochlorothiazide) or at pH 7-10 (hydrochlorothiazide in the mixture). A number of new degradation products were detected and some of them were identified by our LC-DAD and LC-MS methods. In the stressed individual samples, (phenylmethyl)hydrazine and 1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide were observed for the first time. Interactions between dihydralazine and hydrochlorothiazide in the mixture were confirmed by additional degradation products, e.g., 2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1,4-trioxide.

Chemical stability and interactions in a new antihypertensive mixture containing indapamide and dihydralazine using FT-IR, HPLC and LC-MS methods.

Indapamide and dihydralazine can be combined in fixed-dose formulations because of their complementary actions against hypertension. On the other hand, combined formulations present the problem of chemical interactions between the active ingredients, e.g. accelerated degradation of constituents or generation of quite new degradation products. Therefore, the main goal of the present study was to examine the chemical stability of indapamide and dihydralazine, as individuals and as a mixture, to detect potent interactions between both constituents, using FT-IR, HPLC and LC-MS methods. It was clearly shown that both drugs degraded more when they were in the mixture, i.e. indapamide was degraded more under high temperature/high humidity while dihydralazine was more sensitive to UV/VIS light. In solutions, indapamide was sensitive to strong acidic and strong alkaline conditions while dihydralazine degraded at pH ≥ 7. Generally, the process of degradation of indapamide and dihydralazine followed first order kinetics. The fastest degradation of both indapamide and dihydralazine was found at pH ≥ 10. Several degradation products of indapamide and dihydralazine were detected and identified by our LC-MS method. Interactions between both drugs were confirmed by detection of new degradation products of indapamide, i.e. 4-chloro-3-sulfamoylbenzamide and 4-chloro-3-(formylsulfamoyl)-N-(2-methyl-2,3-dihydro-1H-indol-1-yl)benzamide, only in the presence of dihydralazine.

Correction: Chemical stability and interactions in a new antihypertensive mixture containing indapamide and dihydralazine using FT-IR, HPLC and LC-MS methods.

[This corrects the article DOI: 10.1039/C8RA06707D.].

Molecular structure and vibrational spectra of 2,2',4,4',6-pentabromodiphenyl ether (BDE 100).

In this work, FT-IR ATR and Raman (laser line 532nm) spectra of 2,2',4,4',6-pentabromodiphenyl ether (BDE 100) have been recorded in the range of 4000-650 and 4000-100cm-1, respectively. A combined experimental and theoretical approach (DFT/B3LYP/6-311++g** and aug-cc-pVDZ) was used to study molecular structure of BDE 100. Optimization of geometry in the gas phase at these levels of theory indicated that the BDE 100 has skew conformation. The detailed assignment of IR and Raman bands of BDE 100 was done on the basis of calculated results for the most stable conformer. The scaled theoretical frequencies are in good agreement with the experimental ones. Both experimental and theoretical IR and Raman spectra of BDE 100, one of the members of the family of flame retardants, are presented here for the first time.

(-)-R-mevalonolactone studied by ROA and SERS spectroscopy.

Here we present for the first time the experimental and theoretical (DFT/B3LYP/6-311++G**) Raman optical activity (ROA) spectra of (-)-R-mevalonic acid as the δ-lactone form in neat liquid and in the aqueous solution. Quantum chemical calculations show the conformational diversity of (-)-R-mevalonolactone originated from small energy differences between the various conformation of the six-membered ring and the arrangement of the hydroxyl group. According to calculations, the investigated compound takes predominantly the chair conformation with the hydroxyl group in axial position, but the contribution of the other chair and boat conformers in the equilibrium at room temperature is not negligible. Additionally, we present normal Raman and the surface enhanced Raman (SERS) spectra of (-)-R-mevalonolactone adsorbed on the colloidal silver.

Pathological changes in the biochemical profile of the liver in atherosclerosis and diabetes assessed by Raman spectroscopy.

Raman microspectroscopic imaging has been utilized for the investigation of pathological changes in the liver induced by diabetes and atherosclerosis.

Experimental (FT-IR and FT-RS) and theoretical (QC-DFT) studies of vibrational modes and molecular structure of new low-temperature phases of [Ru(NH3)6](BF4)3 and [Ru(NH3)6](ClO4)3.

Vibrational spectra of [Ru(NH(3))(6)](BF(4))(3) and [Ru(NH(3))(6)](ClO(4))(3) in their novel low-temperature solid phases were recorded using FT-IR and FT-RS. Quantum chemical calculations of molecular structure and vibrational modes were made separately for BF(4)(-),ClO(4)(-)and[Ru(NH(3))(6)](3+) ions. The harmonic vibrational frequencies and the related IR and RS bands intensities and activities, respectively, were simulated at the B3LYP/6-311+G(d) and B3LYP/LANL2TZ(f)/6-311+G(d,p) levels of the DFT. Full interpretation of the vibrational spectra has been carried out with the aid of the normal coordinate analysis. The assignments of the vibrational modes were based on the potential energy distribution data, using the MOLVIB program. The calculated Ru-N stretching frequencies are too low, in comparison to experiment, which indicates that B3LYP method underestimates the Ru-N bond strength. Some values of calculated and measured (obtained from X-ray) bond lengths and angles were also compared. Conclusions about possible interactions inside and between the complex ions were drawn.

Raman optical activity: a powerful technique to investigate essential oil components.

The theory and some applications of Raman Optical Activity (ROA) towards terpene analysis are presented. With this technique, vibrational optical activity from chiral molecules can be measured providing their absolute configuration. This short review provides data obtained for pinene, verbenone, menthol, camphor, carenes and related molecules. The ROA technique seems to be a powerful tool which permits correlation between the properties of biocompounds and their structure.