Molecular Organization of Nalidixate Conjugated Calixarenes in Bacterial Model Membranes Probed by Molecular Dynamics Simulation and Langmuir Monolayer Studies

Abstract

Two p-tert-butylcalix[4]arene derivatives bearing one or two nalidixic acid groups connected to the lower rim of p-tert-butylcalix[4]arene through the propylenic spacer were studied upon interaction with model bacterial membranes. Indeed, these derivatives were developed recently as new macrocyclic antibiotic carriers for antibacterial therapy. To obtain molecular level information about the interaction between the calixarene conjugates and a membrane lipid, atomistic molecular dynamics simulation, as well as surface pressure, surface potential, polarization modulation infrared reflection-absorption spectroscopy, and Brewster angle microscopy studies of 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine (DMPE)-calixarene derivative films were performed. The results obtained indicate that the interaction between the calixarene derivatives and DMPE occurs via the phosphate and carbonyl groups present in the lipid. Although both calixarene derivatives increase the chain tilt and conformational disordering of the DMPE molecules, these effects are more important in the case of the monosubstituted derivative. Importantly, the two derivatives have an opposite impact on hydration of the phosphoglyceride polar head.

The Molecular Bases of the Interaction between a Saponin from the Roots of Gypsophila paniculata L. and Model Lipid Membranes

“…The interactions between GOTCAB saponin and the model cell membranes were investigated experimentally using Langmuir film technique [ 22 , 23 , 24 ]. The monomolecular films were formed with ternary SM/POPC/CHOL lipid mixtures containing biologically relevant 10 or 30% of cholesterol [ 25 , 26 ]; films containing 50 mol% of cholesterol were used as well.…”

A Study of the Interaction between a Family of Gemini Amphiphilic Pseudopeptides and Model Monomolecular Film Membranes Formed with a Cardiolipin

“…33, 34 We want to mention that thermodynamic terms used here were defined in our previous papers. 35,36 Namely, in accordance with the definition of Gibbs energy of mixing, ΔG mix = G − (x 1 G 1 + x 2 G 2 ), eq 2 gives ΔG mix instead of ΔG exc given by Goodrich at al. 33 and Bacon et al 34 Polarization-Modulation Infrared Reflection−Absorption Spectroscopy (PM-IRRAS).…”

“…The collapse surface pressure (Π coll ), area per molecule at collapse pressure ( A coll ) and collapse surface potential (Δ V coll ) values of the monolayers, as well as the compressibility modulus ( C s –1 ) defined as were determined directly from the surface pressure–area (Π– A ) and surface potential-area (Δ V – A ) isotherms. The excess free enthalpy of mixing, Δ G mix , was also determined from Π– A isotherms using the following formula: where A 12 is the mean molecular area in the mixed monolayer at a given surface pressure, A 1 and A 2 are the mean molecular areas of the pure components 1 and 2 at the same surface pressure, and x 1 and x 2 are the mole fractions of the two lipid components in the mixed film. , We want to mention that thermodynamic terms used here were defined in our previous papers. , Namely, in accordance with the definition of Gibbs energy of mixing, Δ G mix = G – ( x 1 G 1 + x 2 G 2 ), eq gives Δ G mix instead of Δ G exc given by Goodrich at al . and Bacon et al…”

Molecular Dynamics Simulations to Study Drug Delivery Systems

“…Within the fully atomistic treatment, only few nanocarriers could be completely simulated. This is the case, for instance, for cyclodextrins [30,31], calixarenes [32], dendrimers of low numbers [33], and so on. Nevertheless, in most cases, in order to get information of the nanoparticles, further approaches should be done:…”