1 Department of Chemistry, Universidade Estadual de Ponta Grossa, Ponta Grossa, Par84030-900, Brazil. karen.woh@gmail.com.
2 Department of Physics, Universidade Estadual de Ponta Grossa, Ponta Grossa, Paraná 84030-900, Brazil.
3 Academic Department of Mathematic, Universidade Federal Tecnológica do Paraná - Campus Ponta Grossa, Ponta Grossa, Paraná 84016-210, Brazil.
4 Department of Organic Chemistry, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul 91501-970, Brazil.
5 Instituto de Ciências Ambientais, Químicas e Farmacêuticas, Universidade Federal de São Paulo, Diadema, São Paulo (SP) 09972-970, Brazil.
6 Department of Chemistry and Biochemistry and Concordia Centre for NanoScience Research, Concordia University, 7141 Sherbrooke Street West, Montreal, Québec H4B 1R6, Canada.

The antibacterial activity of p-tert-butylcalix[6]arene and its effect on a membrane model: molecular dynamics and Langmuir film studies.

Phys Chem Chem Phys. 2020 Mar 03;:

Authors: Wrobel EC, de Lara LS, do Carmo TAS, Castellen P, Lazzarotto M, de Lázaro SR, Camilo A, Caseli L, Schmidt R, DeWolf CE, Wohnrath K

Abstract

The antibacterial activity of a calixarene derivative, p-tert-butylcalix[6]arene (Calix6), was assessed and was shown not to inhibit the growth of E. coli, S. aureus and B. subtilis bacteria. With the aim of gaining more insights into the absence of antibacterial activity of Calix6, the interaction of this derivative with DPPG, a bacterial cell membrane lipid, was studied. Langmuir monolayers were used as the model membrane. Pure DPPG and pure Calix6 monolayers, as well as binary DPPG:Calix6 mixtures were studied using surface pressure measurements, compressional modulus, Brewster angle and fluorescence microscopies, ellipsometry, polarization-modulation infrared reflection absorption spectroscopy and molecular dynamics simulations. Thermodynamic properties of the mixed monolayers were additionally calculated using thermodynamic parameters. The analysis of isotherms showed that Calix6 significantly affects the DPPG monolayers, modifying the isotherm profile and increasing the molecular area, in agreement with the molecular dynamics simulations. The presence of Calix6 in the mixed monolayers decreased the interfacial elasticity, indicating that calixarene disrupts the strong intermolecular interactions of DPPG hindering its organization into a compact arrangement. At low molar ratios of Calix6, the DPPG:Calix6 interactions are preferentially attractive, due to the interactions between the hydrophobic tails of DPPG and the tert-butyl groups of Calix6. Increasing the proportion of calixarene generates repulsive interactions. Calix6 significantly affects the hydrophobic tail organization, which was confirmed by PM-IRRAS measurements. Calix6 appears to be expelled from the mixed films at a biologically relevant surface pressure, p = 30 mN m-1, indicating a low interaction with the cell membrane model related to the absence of antibacterial activity.

PMID: 32124897 [PubMed - as supplied by publisher]