Antibacterial Activity of Various Morphologies of Films Based on Guanidine Derivatives of Pillar[5]arene: Influence of the Nature of One Substitute on Self-assembly.

The progress of the pillar[5]arene chemistry allowed us to set out a new concept on application of the supramolecular assemblies to create antimicrobial films with variable surface morphologies and biological activities. Antibacterial films were derived from the substituted pillar[5]arenes containing nine pharmacophoric guanidine fragments and one thioalkyl substituent. Changing the only thioalkyl fragment in the macrocycle structure made it possible to control the biological activity of the resulting antibacterial coating. Pretreatment of the surface with aqueous solution of the amphiphilic pillar[5]arenes reduced the biofilm thickness by 56 ± 10% of Gram-positive Staphylococcus aureus in the case of the pillar[5]arene containing a thiooctyl fragment and by 52 ± 7% for the biofilm of Gram-negative Klebsiella pneumoniae in the case of pillar[5]arene containing a thiooctadecyl fragment. Meanwhile, the cytotoxicity of the synthesized macrocycles was examined at a concentration of 50 µg/mL, which was significantly lower than that of bis-guanidine-based antimicrobial preparations.

Toward Pathogenic Biofilm Suppressors: Synthesis of Amino Derivatives of Pillar[5]arene and Supramolecular Assembly with DNA.

New amino derivatives of pillar[5]arene were obtained in three stages with good yields. It was shown that pillar[5]arene containing thiaether and tertiary amino groups formed supramolecular complexes with low molecular weight model DNA. Pillar[5]arene formed complexes with a DNA nucleotide pair at a ratio of 1:2 (macrocycle/DNA base pairs), as demonstrated by UV-visible and fluorescence spectroscopy. The association constants of pillar[5]arene with DNA were lgKass1:1 = 2.38 and lgKass1:2 = 5.07, accordingly. By using dynamic light scattering and transmission electron microscopy, it was established that the interaction of pillar[5]arene containing thiaether and tertiary amino groups (concentration of 10-5 M) with a model nucleic acid led to the formation of stable nanosized macrocycle/DNA associates with an average particle size of 220 nm. It was shown that the obtained compounds did not exhibit a pronounced toxicity toward human adenocarcinoma cells (A549) and bovine lung epithelial cells (LECs). The hypothesis about a possible usage of the synthesized macrocycle for the aggregation of extracellular bacterial DNA in a biofilm matrix was confirmed by the example of St. Aureus. It was found that pillar[5]arene at a concentration of 10-5 M was able to reduce the thickness of the St. Aureus biofilm by 15%.

Self-Healing Thiolated Pillar[5]arene Films Containing Moxifloxacin Suppress the Development of Bacterial Biofilms.

Polymer self-healing films containing fragments of pillar[5]arene were obtained for the first time using thiol/disulfide redox cross-linking. These films were characterized by thermogravimetric analysis and differential scanning calorimetry, FTIR spectroscopy, and electron microscopy. The films demonstrated the ability to self-heal through the action of atmospheric oxygen. Using UV-vis, 2D 1H-1H NOESY, and DOSY NMR spectroscopy, the pillar[5]arene was shown to form complexes with the antimicrobial drug moxifloxacin in a 2:1 composition (logK11 = 2.14 and logK12 = 6.20). Films containing moxifloxacin effectively reduced Staphylococcus aureus and Klebsiella pneumoniae biofilms formation on adhesive surfaces.

Water-soluble pillar[5]arene sulfo-derivatives self-assemble into biocompatible nanosystems to stabilize therapeutic proteins.

Pillar[5]arenes containing sulfonate fragments have been shown to form supramolecular complexes with therapeutic proteins to facilitate targeted transport with an increased duration of action and enhanced bioavailability. Regioselective synthesis was used to obtain a water-soluble pillar[5]arene containing the fluorescent label FITC and nine sulfoethoxy fragments. The pillar[5]arene formed complexes with the therapeutic proteins binase, bleomycin, and lysozyme in a 1:2 ratio as demonstrated by UV-vis and fluorescence spectroscopy. The formation of stable spherical nanosized macrocycle/binase complexes with an average particle size of 200 nm was established by dynamic light scattering and transmission electron microscopy. Flow cytometry demonstrated the ability of macrocycle/binase complexes to penetrate into tumor cells where they exhibited significant cytotoxicity towards A549 cells at 10-5-10-6 M while maintaining the enzymatic activity of binase.

Metallo-Supramolecular Coordination Polymers Based on Amidopyridine Derivatives of Pillar[5]arene and Cu(II) and Pd(II) Cations: Synthesis and Recognition of Nitroaromatic Compounds.

Decasubstituted pillar[5]arenes containing amidopyridine fragments have been synthesized for the first time. As was shown by UV-vis spectroscopy, the pillar[5]arenes with p-amidopyridine fragments form supramolecular associates with Cu(II) and Pd(II) cations in methanol in a 2:1 ratio. Using a sol-gel approach these associates are transformed into metallo-supramolecular coordination polymers (supramolecular gels) which were characterized as amorphous powders by scanning electron microscopy (SEM) and dynamic light scattering (DLS). The powders are able to selectively adsorb up to 46% of nitrophenols from water and were incorporated into an electrochemical sensor to selectively recognize them in aqueous acidic solution.

Towards new nanoporous biomaterials: self-assembly of sulfopillar[5]arenes with vitamin D3 into supramolecular polymers.

Novel water-soluble, deca-substituted pillar[5]arenes containing thiasulfate and thiacarboxylate fragments were synthesized and characterized. UV-vis, 2D 1H-1H NOESY and DOSY NMR spectroscopy revealed the ability of pillar[5]arenes containing thiasulfate fragments to form an inclusion complex with cholecalciferol (vitamin D3) in a 1 : 2 ratio (lg Kass = 2.2). Using DLS and SEM it was found that upon concentration and/or evaporation of the solvent, the supramolecular polymer (pillar[5]arene/vitamin D3 (1 : 2)) forms a porous material with an average wall diameter of 53 nm. It was shown that the supramolecular polymer is stable during photolysis by UV radiation (k1 = 1.7 × 10-5 s-1).