Qualitative and quantitative sensing of some pharmaceutical compounds by calix[4]arene amide and Schiff base derivatives in aqueous media

In this study, it was aimed to qualitatively and quantitatively determine the pharmaceutical compounds, which are the active ingredients of drugs, the use of which has increased in recent years, in aqueous media. For this, spectroscopic and QCM sensor studies were performed using calix[4]arene Schiff base and amide derivatives containing different functional groups. Using the Rhodamine B and fluorescein structures, calix[4]arene K-Rh and K-Fl derivatives, 8-hydroxyquinoline, 5-phenylazo-8-hydroxyquinoline, benzathiazole and semicarbazide structures, respectively, were used as calix[4]arene K-8HQ, K-8HA, K-Ben and K-SK derivatives were synthesized, and the structures of all compounds were confirmed by 1H-NMR spectroscopy. Some of these compounds were later selected pharmaceutical compounds (ascorbic acid (AA), diphenhydramine (DIF), 4-dimethylaminoantipyrine (DMAP), trimethoprim (TRI), sulfamethoxazole (SUL), atenolol (ATE), naproxen (NAP), phenytoin (FEN), ibuprofen (IBU) and paracetamol (PAR)) were first examined spectroscopically. QCM sensor studies were carried out for compounds with spectroscopic sensor properties. When the spectroscopic sensor properties of the K-Rh derivative against different pharmaceutical compounds in ethanol-water environment were examined, it was seen that it was a fluorimetrically selective and sensitive sensor against AA. Here, it was evaluated that the observation of a severe emission at 585 nm with the ring opening reaction on the structure was effective in the emergence of the sensor feature of the K-Rh derivative. It was determined that K-Rh:AA complexation occurred at a ratio of 1:1 and the LOD value of the sensor was 2.59 µM. QCM studies for AA of the K-Rh derivative were also performed. In order to see the effect of the functional group, rhodamine groups were found to be effective in the detection of AA when compared with the calix[4]arene K-4 derivative carrying the aldehyde group. It was determined that there was a 1:1 interaction between K-Rh and AA in detection from stoichiometric ratio values. This showed that both the spectroscopic method and the QCM method confirmed each other at this point. When the spectroscopic sensor properties of the K-Fl derivative against different pharmaceutical compounds in acetonitrile-water medium were examined, no significant results were observed. Then, as a second method, when the spectroscopic sensor properties of the K-Fl derivative against different cations were examined under the same conditions, it was seen that it was a colorimetrically selective and sensitive sensor against Cu2+ ion. Here, it was evaluated that the strong absorption maximum at 535 nm, depending on the fluorescein groups on the structure, was effective in the emergence of the sensor feature of the K-Fl derivative. It was determined that K-Fl:Cu2+ complexation occurred at a ratio of 1:2 and the LOD value of the sensor was 5.3 µM. In the continuation of the method, when different pharmaceutical compounds were added to the K-F1:Cu2+ complex, it was observed that a new absorption maximum was formed for FEN colorimetrically at 652 nm. At the same time, fluorimetrically, it was observed that the color of the solution changed with the addition of FEN and a severe emission occurred at 518 nm, forcing the fluorescein ring of the formed complex to open. In addition, when the spectroscopic sensor properties of the K-Fl derivative against different pharmaceuticals in ethanol-water environment were examined, changes in the fluorescence spectra were observed for ATE, NAP, FEN and IBU. However, due to the basic character of the relevant pharmaceutical compounds, it was determined that the ring was opened not because of complexation, but because of the change in the pH of the environment. Then, when the spectroscopic sensor properties of the K-Fl derivative against different cations in the ethanol-water environment were examined, a severe emission was observed at 518 nm due to the opening of the fluorescein ring for the Hg2+ ion. It was determined that K-Fl:Hg2+ complexation occurred at a ratio of 1:2 and the LOD value of the sensor was 0.15 µM. No significant change was observed when different pharmaceutical compounds were added to the K-F1:Hg2+ complex. When the spectroscopic sensor properties of the K-8HA derivative against different pharmaceutical compounds in acetonitrile-water medium were examined, no significant results were observed. As a second method, when the spectroscopic sensor properties of the K-8HA derivative against different cations were examined under the same conditions, there was no significant change. On top of that, when the spectroscopic sensor properties of the 8-hydroxyquinoline-functionalized K-8HQ derivative, which has a similar structure but does not contain azo group, against different pharmaceutical compounds in acetonitrile-water medium, no significant change was observed. However, as a second method, when the spectroscopic sensor properties of the K-8HQ derivative against different cations were examined under the same conditions, it was seen that it was a colorimetrically selective and sensitive sensor against Cu2+ ion. Here, it was evaluated that the K-8HQ derivative gave a strong absorption maximum at 490 nm depending on the 8-hydroxyquinoline groups on the structure. It was determined that K-8HQ:Cu2+ complexation occurred at a ratio of 1:1 of the and the LOD value of the sensor was 3 µM. In the continuation of the method, when different pharmaceutical compounds were added to the K-8HQ:Cu2+ complex, no fluorimetric change was observed, while colorimetrically only color change was observed for DMAP, but the stability of the formed K-8HQ:DMAP complex was weak. When the spectroscopic sensor properties of the K-Ben derivative against different pharmaceutical compounds in DMSO-water medium were examined, no significant results were observed. Then, as a second method, when the spectroscopic sensor properties of the K-Ben derivative against different cations were examined under the same conditions, it was seen that it was a fluorimetrically selective and sensitive sensor against Zn2+ ion. Here, it was evaluated that the K-Ben derivative's intense emission at 480 nm, depending on the benzothiazole groups on the structure, was effective in the emergence of the sensor feature. It was determined that K-Ben:Zn2+ complexation occurred at a ratio of 1:1 and the LOD value of the sensor was 2.6 µM. When different pharmaceutical compounds were added to the K-Ben:Zn2+ complex, it was observed that the complex was disrupted in the case of DIF and the emission at 480 nm was quenched. QCM studies for DIF of the K-Ben derivative were also performed. When the frequency changes obtained were examined, it was observed that as the concentration value increased, the frequency change increased, but the rate of increase gradually decreased. It was determined that there was a 1:1 interaction between K-Ben and DIF in detection from stoichiometric ratio values. This showed that both the spectroscopic method and the QCM method confirmed each other at this point. When the detection studies of different pharmaceutical compounds in aqueous medium of the K-SK derivative coated QCM sensor were performed, it was observed that the highest frequency changes occurred for NAP and IBU, and the lowest frequency change was obtained for AA. In all QCM studies, the effect of the coating thickness was examined and it was observed that the stoichiometric ratio values decreased as the coating thickness increased. The main reason for this was considered to be the closure of the sensing areas due to the large amount of sensing substance on the surface and the formation of multiple layers by overlapping the molecules during the coating process. Although stoichiometric high detection was achieved at low coating values, the detection capacity was low. In QCM studies, the adsorption parameters were determined by drawing the Langmuir, Freundlich and Scatchard isotherms, since the interactions are based on the adsorption process.