Four sulfonamide derivatives with a methoxyphenyl moiety, namely N-{4-[(2-methoxyphenyl)sulfamoyl]phenyl}acetamide (1a), N-{4-[(3-methoxyphenyl)sulfamoyl]phenyl}acetamide (1b), 4-amino-N-(2-methoxyphenyl)benzenesulfonamide (2a) and 4-amino-N-(3-methoxyphenyl)benzenesulfonamide (2b), have been synthesized and characterized physiochemically by CHNS, MS, FT-IR, ¹H NMR, ¹³C NMR, PXRD and TG methods. Crystal structures were determined by SC-XRD and their conformational and noncovalent interaction properties were examined by both experimental and theoretical (HS, MEPS, NBO, dimerization energy, QTAIM) methods. The conformational flexibility of the bridge connecting two phenyl rings was studied and minimum-energy conformations were theoretically found. The packing architecture and hydrogen bond networks were described by graph set notation. Hirshfeld surface analysis revealed regions of stronger contacts and allowed us to indicate the relative contributions of different noncovalent contacts in the crystal packing. MEPS calculations helped to distinguish the electron rich and electron poor regions and to find the best H-bond donors and acceptors. The use of the QTAIM method enabled us to explain the influence of functional groups and molecular arrangement on the strength of noncovalent interactions in the crystals and overall packing efficiency.

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.