RESUMO
A novel neutral tetranitrosyl iron complex {[Fe(H2O)4]2+[FeR2(NO)2]22-}·4H2O (1) with R = 5-(3-pyridyl)-4H-1,2,4-triazole-3-thiolyls (C7H5N4S), which is a supramolecular ensemble, has been synthesized and studied. As follows from X-ray diffraction analysis, this is an octahedral Fe2+complex (Lewis acid) with two monoanionic dinitrosyl groups [FeR2(NO)2]- (Lewis base) and 4 water molecules as the ligands. As follows from Mössbauer spectra, the coordinating Fe2+ ion is in a low-spin state S = 0, and the dinitrosyl Fe+ ion is in a low-spin state S = 1/2. According to the data of EPR spectroscopy, mass-spectrometry and amperometry, complex 1 in solution forms dinitrosyl particles of [Fe(C7H6N4S-H)2(NO)2]- composition, which are responsible for NO generation. In addition, complex 1 was shown to be a 5-6 times more efficient phosphodiesterase (PDE) inhibitor at 5 × 10-5 M and 10-4 M concentrations than its thioligand. Probable binding sites of the [FeR2(NO)2]- ligand for the bovine PDE1B model have been determined by molecular docking and quantum-chemical calculations.
RESUMO
The accuracy of the ion flight time measurement in the time-of-flight mass spectrometer is critical to achieving high resolution. The pulse amplitude variation of the detector pulses leads to the registration time spread at a given pulse detection threshold. This time spread can be eliminated by determining the position of the pulse apex. To determine the position of the pulse apex, the output of the ion detector is fed simultaneously to the two channels of the time-to-digital converter. In this case, the first channel is set to register the leading edge, and the second channel is set to register the trailing edge of the pulse. Using a simple processing of the received data, the position of the pulse tip is determined. Thus, the dependence of the temporal position of the peak on the pulse amplitude is largely eliminated. Examples are given, and the efficiency of using this algorithm to increase the resolution of time-of-flight mass spectral peak registration is demonstrated.
RESUMO
The cytotoxic activity of a series of dinitrosyl iron complexes (DNICs) with thioureas against cells of different origin has been studied in this work. The cytotoxicity of the studied DNICs proved to be substantially different depending on the structure of the complexes and cell line. Complexes with thiourea and 1,3-dimethylthiourea were found to induce notable cell death in different cell lines of both cancerous and non-cancerous origin, while the N-ethylthiourea-bearing complex induced cell death in cells derived from brain tumors. The studied DNICs effectively release NO while decomposing in solutions, as follows from the electrochemical analysis. It was found that the cytotoxic effects of the studied DNICs did not correlate with their NO-donating ability, hence suggesting that their cytotoxic activity is, in a big part, defined by the long-lived nitrosyl iron-sulfur intermediates formed during the decomposition of the complexes. The structures of the products formed upon hydrolytic decomposition of all studied DNICs have been studied by electrospray ionization mass spectrometry. Stable high-molecular cluster ions containing NO groups namely [Fe4S3(NO)7]- (Roussin's "black salt" anion), [Fe4S3(NO)5]-, [Fe4S4(NO)4]-, [Fe4S3(NO)4]- and [Fe4S3(NO)6]- have been detected in the solution of the N-ethylthiourea-bearing complex. The mechanism of Roussin's "black salt" anion formation in a solution of DNIC with N'-ethylthiourea was studied using density functional theory. This moved us near understanding the reasons for the formation of biologically active intermediates upon the decomposition of the complex with N'-ethylthiourea, which are apparently responsible for the unique antiglioma activity of the complex.
