The interactions of compounds with DNA have been studied since the recognition of the role of nucleic acid in organisms. The design of molecules which specifically interact with DNA sequences allows for the control of the gene expression. Determining the type and strength of such interaction is an indispensable element of pharmaceutical studies. Cognition of the therapeutic action mechanisms is particularly important for designing new drugs. Owing to their sensitivity, simplicity, and low costs, electrochemical methods are increasingly used for this type of research. Compared to other techniques, they require a small number of samples and are characterized by a high reliability. These methods can provide information about the type of interaction and the binding strength, as well as the damage caused by biologically active molecules targeting the cellular DNA. This review paper summarizes the various electrochemical approaches used for the study of the interactions between pharmaceuticals and DNA. The main focus is on the papers from the last decade, with particular attention on the voltammetric techniques. The most preferred experimental approaches, the electrode materials and the new methods of modification are presented. The data on the detection ranges, the binding modes and the binding constant values of pharmaceuticals are summarized. Both the importance of the presented research and the importance of future prospects are discussed.
Cyclodextrin-based nanosponges (CD-NS) are a novel class of polymers cross-linked with a three-dimensional network and can be obtained from cyclodextrins (CD) and pyromellitic dianhydride. Their properties, such as their ability to form an inclusion complex with drugs, can be used in biomedical science, as nanosponges influence stability, toxicity, selectivity, and controlled release. Most pharmaceutical research use CD-NS for the delivery of drugs in cancer treatment. Application of molecular targeting techniques result in increased selectivity of CD-NS; for example, the addition of disulfide bridges to the polymer structure makes the nanosponge sensitive to the presence of glutathione, as it can reduce such disulfide bonds to thiol moieties. Other delivery applications include dermal transport of pain killers or photosensitizers and delivery of oxygen to heart cells. This gives rise to the opportunity to transition to medical scaffolds, but more, in modern times, to create an ultrasensitive biosensor, which employs the techniques of surface-modified nanoparticles and molecularly imprinted polymers (MIP). The following review focuses on the biomedical research of cyclodextrin polymers cross-linked via dianhydrides of carboxylic acids.
Our former studies delivered a strong evidence that water indirectly treated with low-temperature, low-pressure glow plasma of low frequency (GP) changed its structure depending on the atmosphere in which such treatment was performed (air, ammonia, and nitrogen) and on the time of the treatment (0 to 120 min). In every case, water of different physicochemical characteristics and interesting biological functions was produced. Therefore, the relevant studies were extended to treating deionized water with GP under methane. The resulting samples were characterized by means of ultraviolet/visible (UV/VIS), Fourier transformation infrared-attenuated total reflectance (FTIR-ATR), electron spin resonance (ESR) and Raman spectroscopies, differential scanning calorimetry (DSC), thermogravimetry, pH, conductivity, and refractive index. The generated samples of water had entirely different physicochemical properties from those recorded for water treated with GP in the air and under both ammonia and nitrogen. The treatment of water with GP under methane did not produce clathrates hosting methane molecules. Thermogravimetry delivered an evidence that the treatment with GP increased the aqueous solubility of methane. That solubility non-linearly changed against the treatment time.
Deionized, tap and two kinds of commercially available mineralized water, after supplementation with ammonia, were treated with low-pressure, low-temperature glow plasma (GP) of low frequency. Treating hard water with ammonia provided the removal of permanent and temporary water hardness already at room temperature. On such treatment, mineralized water supplemented with ammonia was partly demineralized. Precipitated rhombohedral deposit from hard water did not turn into scale even when maintained in suspension for 3 days at around 90°C. In such manner, the use of other chemicals for prevention from the scale formation and/or for the scale removal is entirely dispensable. The rate and yield of precipitation depended on the concentration of admixed ammonia and the GP treatment time. Ammonia served as a ligand of calcium, magnesium and ferric central atoms of corresponding salts constituting the hardness. Moreover, ammonia constituting the atmosphere of the treatment was arrested inside aqueous clathrates. So, stabilized ammonia solutions could potentially be utilized as an environmental-friendly nitrogen fertilizer. The precipitate could also be utilized for the same purpose.
The discovery and introduction of the switchSense technique in the chemical laboratory have drawn well-deserved interest owing to its wide range of applications. Namely, it can be used to determine the diameter of proteins, alterations in their tertiary structures (folding), and many other conformational changes that are important from a biological point of view. The essence of this technique is based on its ability to study of the interactions between an analyte and a ligand in real time (in a buffer flow). Its simplicity, on the other hand, is based on the use of a signaling system that provides information about the ongoing interactions based on the changes in the fluorescence intensity. This technique can be extremely advantageous in the study of new pharmaceuticals. The design of compounds with biological activity, as well as the determination of their molecular targets and modes of interactions, is crucial in the search for new drugs and the fight against drug resistance. This article presents another possible application of the switchSense technique for the study of the binding kinetics of small model molecules such as ethidium bromide (EB) and selected sulfonamide derivatives with DNA in the static and dynamic modes at three different temperatures (15, 25, and 37 °C) each. The experimental results remain in very good agreement with the molecular dynamics docking ones. These physicochemical insights and applications obtained from the switchSense technique allow for the design of an effective strategy for molecular interaction assessments of small but pharmaceutically important molecules with DNA.
Antibiotics play a key role in the fight against bacterial diseases. However, bacteria quickly learn how to minimize the effects of antibiotics and strengthen their resistance. Thus, the fight against them becomes more and more difficult and there is a constant search for new bactericidal compounds. It is important in this type of search to determine the basic properties of compounds such as pK a , hydrogen bond formation, or hydrophobicity. Here, we present the results of our in silico study of five sulfonamide derivatives differing in alkylamine substituent length. Based on our results, we propose a model of three possible pK a values for each of the studied compounds. Interestingly, the use of Muckerman's approach for pK a determination exhibits that theoretical and experimental results are in very good agreement. Intramolecular hydrogen bond formation affects pK a . The strength of the H-bond interaction increases from ethyl to butylamine and then decreases with the elongation of the alkylamine chain. The obtained partition coefficients (expressed here in the value of log P) increase with the number of carbon atoms in the alkylamine chain following Lipinski's rule of five. The presented results provide important structural, physicochemical, and thermodynamic information that allows for the understanding of the influence of some sulfonamides and their possible activity.
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