A series of new peptide dendrimers with amphiphilic surface, designed around a dendronized ornithine (Orn) core were synthesized and characterized by ESI-MS, ¹H-, ¹³C- NMR, and CD spectrometry. An improved antimicrobial potency against S. aureus and E. coli was detected as a result of an increased charge, higher branching and variable lipophilicity of the residues located at the C-terminus. Minimal inhibitory concentration (MIC) values indicated that the selected dendrimers were not sensitive to the physiological concentration of Na⁺ and K⁺ ions (100 mM), but expressed reduced potency at 10 mM concentration of Mg²⁺ and Ca²⁺ ions. Circular dichroism (CD) curves measured under various conditions revealed structure and solvent-dependent curve evolution. ESI-MS studies of gas-phase interactions between selected dendrimers and both anionic (DMPG) and neutral (DMPC) phospholipids revealed the presence of variously charged dendrimer/phospholipid aggregates with 1:1 to 1:5 stoichiometry. The collision-induced fragmentation (CID) of the most abundant [dendrimer/phospholipid]²⁺ ions of the 1:1 stoichiometry demonstrated that the studied dendrimers formed stronger complexes with anionic DMPG. Both phospholipids have higher affinity towards dendrimers with a more compact structure. Higher differences in CID energy necessary for dissociation of 50% of the complex formed by dendrimers with DMPG vs. DMPC (DCID₅₀) correlate with a lower hemotoxicity. Mass spectrometry results suggest that for a particular group of compounds the DCID₅₀ might be one of the important factors explaining selectivity of antimicrobial peptides and their branched analogs targeting the bacterial membrane. Both circular dichroism and mass spectrometry studies demonstrated that dendrimers of N^α- and N^ε-series possess a different conformation in solution and different affinity to model phospholipids, what might influence their specific microbicidal mechanism.

Here we describe the inclusion of the minor-groove binding drug pentamidine in its extended conformation into the macrocyclic cavity of water-soluble carboxylated pillar[5]arene. The artificial host–guest system is manifested as an ensemble of three crystalline forms differing in the pillar[5]arene–pentamidine interaction mode, solvation type, and even stoichiometry. The strong hydrogen bonds of various types of amidinium–carboxylate (between pentamidine and pillar[5]arene) and carboxylic–carboxylate (between adjacent pillar[5]arenes) are realized in all complexes, rigidifying the assembly. However, it seems that more subtle effects, such as local solvation/desolvation, a certain degree of flexibility of both the host and guest, and variable protonation/deprotonation state of the pillar[5]arene substituents, play significant roles in the peculiar crystallization behavior of the system. The snapshots of three crystal structures highlighting various binding geometries and intermolecular interaction modes between the same host and guest present exciting opportunities in terms of more holistic models of the host–guest systems, shifting from focusing our attention on “visible interactions” in one crystal structure to the appreciation of many subtle effects playing a combined role in the host–guest chemistry.

Interactions between anions and synthetic macrocyclic receptors belong to the extensively explored area of research due to the particularly important functions of anions in biological and environmental sciences. Structures of anion-macrocycle complexes are closely related to their function, highlighting the importance of structural analysis of the complexes. Here, we discuss the application of ion mobility mass spectrometry (IM-MS) and theoretical calculations to the structural analysis of tetralactam macrocycles (M) with varying flexibility and structural properties, and their complexes with anions [M + X]⁻. Collision cross section (CCS) values obtained from both direct drift tube (DT) and indirect using traveling-wave (TW) IM-MS measurements supplemented by theoretical calculations were successfully used to describe the structural properties of various macrocycle-anion complexes, proving the suitability of the IM-MS approach for sensitive, selective, and fast detection of anion complexes and characterization of their structures and conformations.