A New Approach for Voltammetric Determination of Nefopam and its Metabolite

In present paper we described a new simple voltammetric method of determination of nefopam alkaloid and its metabolite – N‐oxide. N‐oxide of nefopam is reduced at the dropping mercury electrode (DME) and silver solid amalgam electrodes (AgSAE), which can effectively replace mercury and chemically modified electrodes. The reduction consists of two one‐electron stages each accompanied with one proton transfer. N‐oxide of nefopam can be obtained from nefopam substance by oxidation with potassium peroxymonosulfate. It was studied the effect of various factors on N‐oxide quantitative yield (pH, oxidation duration, reagents concentration) as well as on the reduction of N‐oxide at DME and p‐AgSAE (pH, the nature of background electrolyte, potential and time of accumulation). It was showed that the reduction current linearly increased with increasing of concentration of analgesic. Limit of quantiation is 10^?6 mol L^?1 at DME and 10^?7 mol L^?1 at p‐AgSAE. The developed method was applied for the analysis of commercial drug solution for injection “Nefopam” with recovery of 96.7 %, as well as for the spiked human urine samples. Excellent repeatability with a relative standard deviation below 5 % was achieved.     

ROS‐Responsive N‐Alkylaminoferrocenes for Cancer‐Cell‐Specific Targeting of Mitochondria

Mitochondrial membrane potential is more negative in cancer cells than in normal cells, allowing cancer targeting by delocalized lipophilic cations (DLCs). However, as the difference is rather small, these drugs affect also normal cells. Now a concept of pro‐DLCs is proposed based on an N‐alkylaminoferrocene structure. These prodrugs are activated by the reaction with reactive oxygen species (ROS) forming ferrocenium‐based DLCs. Since ROS are overproduced in cancer, the high‐efficiency cancer‐cell‐specific targeting of mitochondria could be achieved as demonstrated by fluorescence microscopy in combination with two fluorogenic pro‐DLCs in vitro and in vivo. We prepared a conjugate of another pro‐DLC with a clinically approved drug carboplatin and confirmed that its accumulation in mitochondria was higher than that of the free drug. This was reflected in the substantially higher anticancer effect of the conjugate.     

Reagentless amperometric formaldehyde-selective biosensors based on the recombinant yeast formaldehyde dehydrogenase

Novel formaldehyde-selective amperometric biosensors were developed based on NAD(+)- and glutathione-dependent formaldehyde dehydrogenase isolated from a gene-engineered strain of the methylotrophic yeast Hansenula polymorpha. Electron transfer between the immobilized enzyme and a platinized graphite electrode was established using a number of different low-molecular free-diffusing redox mediators or positively charged cathodic electrodeposition paints modified with Os-bis-N,N-(2,2'-bipyridil)-chloride ([Os(bpy)(2)Cl]) complexes. Among five tested Os-containing redox polymers of different chemical structure and properties, complexes of osmium-modified poly(4-vinylpyridine) with molecular mass of about 60 kDa containing diaminopropyl groups were selected. The positively charged cathodic paint exhibited the best electron-transfer characteristics. Moreover, the polymer layers simultaneously served as a matrix for keeping the negatively charged low-molecular cofactors, glutathione and NAD(+), in the bioactive layer. Additionally, covering the enzyme/polymer layer with a negatively charged Nafion membrane significantly decreased cofactors leakage and simultaneously enhanced the sensor' stability. The developed sensors revealed a high selectivity to formaldehyde (FA) and a low cross-sensitivity to other substances (such as, e.g. butyraldehyde, propionaldehyde, acetaldehyde, methylglyoxal). The maximum current value was 34.2+/-0.72 microA/mm(2) (3.05 mm diameter electrode) and the apparent Michaelis-Menten constant (K(M)(app)) derived from the FA calibration curves was 120+/-5mM with a linear detection range for FA up to 20mM. The best observed sensitivity for reagentless sensor was 1.8 nA microM(-1) (358 Am(-2)M(-1)). The developed sensors had a good operational and storage stability. The laboratory prototype of the sensor was applied for FA testing in some real samples of pharmaceutical (formidron), disinfectant (descoton forte) and industrial product (formalin). A good correlation was revealed between the concentration values measured using the developed FdDH-based sensor, an enzymatic method and standard chemical methods of FA determination.     

Complexation of Sc(III), Ga(III), In(III) and Ln(III) with Eriochrome Red B

Cyclic linear-sweep voltammetry was used to study the complexation of Sc(III), Ga(III), In(III) and Ln(III) with eriochrome red B (ERB). It was established that all metal ions investigated form complex compounds with azodye having a mole ratio, M(III):ERB = 1:2. The hydroxo forms of M(III) ions, which take part in interaction with ERB, were determined by the Nazarenko method. The stability constants for the formation of these chelates are nearly the same. It was shown that the reduction of the ligand in the complex does not only depend on the peculiarities of complexation, but the processes occurring in pre-electrode layer also influence it.