A series of cone calix[4]arenes modified with 2-azidoethyl groups at one, two (distal or proximal), and four positions of their narrow rims was prepared. These compounds were studied as the azide components of copper(I)-catalyzed azide–alkyne cycloaddition (CuAAC) with arylacetylenes and aryl propargyl ethers. The study showed that relatively mild or much stronger conditions need to be applied for the complete conversion of the azides into the triazoles, and this depended on the number and mutual arrangement of 2-azidoethyl groups at the narrow rims of calix[4]arenes as well as on the alkyne type selected. Under the optimized conditions a series of calixarenes bearing 2-(4-R-1-triazolyl)ethyl or 2-(4-ROCH₂-1-triazolyl)ethyl (R = phenyl, 2-naphthyl) groups at the narrow rims was prepared, and some bis- and tetrakis(triazoles) from the series were studied for their complexation with transition metal cations. The same complexation study was performed for the related calixarenes bearing (1-R-4-triazolyl)methyl (R = 2-naphthylmethyl) substituents. The triazolated calixarenes of both types were efficient at binding the cations, but the complexation preferences and the cation-binding modes were found to depend drastically on the side by which the triazole units were attached to the calixarene core.

The functionality of p-sulfonatocalix[4]arenes can be easily extended using the propargylation/CuAAC reaction sequence, which allows the introduction of up to four substituted triazole units to the narrow rims of the macrocycles while maintaining their cone shapes and water solubility and, thus, biomedical applicability.

The conformational distribution in distally functionalized adamantylated calix[4]tubes was analyzed with NMR and quantum-chemical calculations. Without any intramolecular interactions, ester-, acid-, amino-, alcohol-, isocyanate-, phthalimide- and urea-substituted calixtubes preferred less sterically hindered flattened cone conformers in solution. In contrast, in a non-polar medium (CDCl₃) for calixtubes bearing two 3-carboxymethyl-1-adamantyl or 3-(2-ureidoethyl)-1-adamantyl units, the less sterically preferable flattened cone conformation with bulky substituents connected by intramolecular hydrogen bonds was found to be more favorable. On the other hand, for a calixtube with two positively charged units, only the conformer with distanced substituents was exclusively detected. Thus, the conformational equilibrium in functionalized calix[4]tubes can be controlled by intramolecular hydrogen bonding between appropriately arranged carboxylic groups or urea moieties, or by electrostatic repulsion of positively charged substituents.

Biosensors based on ion-sensitive field effect transistors (ISFETs) combined with aptamers offer a promising and convenient solution for point-of-care testing applications due to the ability for fast and label-free detection of a wide range of biomarkers. Mobile and easy-to-use readout devices for the ISFET aptasensors would contribute to further development of the field. In this paper, the development of a portable PC-controlled device for detecting aptamer-target interactions using ISFETs is described. The device assembly allows selective modification of individual ISFETs with different oligonucleotides. Ta₂O₅-gated ISFET structures were optimized to minimize trapped charge and capacitive attenuation. Integrated CMOS readout circuits with linear transfer function were used to minimize the distortion of the original ISFET signal. An external analog signal digitizer with constant voltage and superimposed high-frequency sine wave reference voltage capabilities was designed to increase sensitivity when reading ISFET signals. The device performance was demonstrated with the aptamer-driven detection of troponin I in both reference voltage setting modes. The sine wave reference voltage measurement method reduced the level of drift over time and enabled a lowering of the minimum detectable analyte concentration. In this mode (constant voltage 2.4 V and 10 kHz 0.1Vp-p), the device allowed the detection of troponin I with a limit of detection of 3.27 ng/mL. Discrimination of acute myocardial infarction was demonstrated with the developed device. The ISFET device provides a platform for the multiplexed detection of different biomarkers in point-of-care testing.