Our computational studies suggest that 3-substituted xanthines are good candidates for tetrad and quadruplex structures. 3-Methylxanthine (3MX) has been synthesized from 7-benzylxanthine, and the existence of tetrameric and octameric aggregates of 3MX with NH 4 + , Na + and K + ions in the gas phase (MS) and in DMSO-d 6 solution (NMR) has been observed. The ''internal'' H-bonds (N1HÁ Á ÁO6) are stronger than the ''external'' ones (N7HÁ Á ÁO2) in these clusters (NMR). Fig. 1 Tetrads composed of 7H-3-methylxanthine (3MX) and different cations [cat + = none, Na + , K + , NH 4 + ; purine atom and spectroscopic (underlined) numbering shown in upper left ring].

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In Rhizobium-legume symbiosis, the bacteria are converted into nitrogen-fixing bacteroids. In many legume species, differentiation of the endosymbiotic bacteria is irreversible, culminating in definitive loss of their cell division ability. This terminal differentiation is mediated by plant peptides produced in the symbiotic cells. In Medicago truncatula more than ∼700 nodule-specific cysteine-rich (NCR) peptides are involved in this process. We have shown previously that NCR247 and NCR335 have strong antimicrobial activity on various pathogenic bacteria and identified interaction of NCR247 with many bacterial proteins, including FtsZ and several ribosomal proteins, which prevent bacterial cell division and protein synthesis. In this study we designed and synthetized various derivatives of NCR247, including shorter fragments and various chimeric derivatives. The antimicrobial activity of these peptides was tested on the ESKAPE bacteria; Enterococcus faecalis, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Escherichia coli as a member of Enterobacteriaceae and in addition Listeria monocytogenes and Salmonella enterica. The 12 amino acid long C-terminal half of NCR247, NCR247C partially retained the antimicrobial activity and preserved the multitarget interactions with partners of NCR247. Nevertheless NCR247C became ineffective on S. aureus, P. aeruginosa, and L. monocytogenes. The chimeric derivatives obtained by fusion of NCR247C with other peptide fragments and particularly with a truncated mastoparan sequence significantly increased bactericidal activity and altered the antimicrobial spectrum. The minimal bactericidal concentration of the most potent derivatives was 1.6 µM, which is remarkably lower than that of most classical antibiotics. The killing activity of the NCR247-based chimeric peptides was practically instant. Importantly, these peptides had no hemolytic activity or cytotoxicity on human cells. The properties of these NCR derivatives make them promising antimicrobials for clinical use.

The self-assembly of small molecular modules interacting through noncovalent forces is increasingly being used to generate functional structures and materials for electronic, catalytic, and biomedical applications. The greatest control over the geometry in H-bond supramolecular architectures, especially in H-bonded supramolecular polymers, can be achieved by exploiting the rich programmability of artificial nucleobases undergoing self-assembly through strong H bonds. Here N(3)-functionalized xanthine modules are described, which are capable of self-associating through self-complementary H-bonding patterns to form H-bonded supramolecular ribbons. The self-association of xanthines through directional H bonding between neighboring molecules allows the controlled generation of highly compact 1D supramolecular polymeric ribbons on graphite. These architectures have been characterized by scanning tunneling microscopy at the solid-liquid interface, corroborated by dispersion-corrected density functional theory (DFT) studies and X-ray diffraction.

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