Structure Dependence of Pyridine and Benzene Derivatives on Interactions with Model Membranes

Abstract

Pyridine based small molecule drugs, vitamins, and cofactors are vital for many cellular processes, but little is known about their interactions with membrane interfaces. These specific membrane interactions of these small molecules or ions can assist in diffusion across membranes or reach a membrane bound target This study explores how minor differences in small molecules (isoniazid, benzhydrazide, isonicotinamide, nicotinamide, picolinamide, and benzamide) can affect their interactions with model membranes. Langmuir monolayer studies of dipalmitoylphosphatidylcholine (DPPC) or dipalmitoylphosphatidylethanolamine (DPPE), in the presence of the molecules listed, show that isoniazid and isonicotinamide affect the DPPE monolayer at lower concentrations than the DPPC monolayer, demonstrating a preference for one phospholipid over the other. The Langmuir monolayer studies also suggest that nitrogen content and stereochemistry of the small molecule can affect the phospholipid monolayers differently. To determine the molecular interactions of the simple N-containing aromatic pyridines with a membrane-like interface, 1H 1D NMR and 1H-1H 2D NMR techniques were utilized to obtain information aboutposition and orientation of the molecules of interest within aerosol-OT (AOT) reverse micelles. These studies show that all six of the molecules reside near the AOT sulfonate headgroups and ester linkages in similar positions, but nicotinamide and picolinamide tilt at the water-AOT interface to varying degrees. Combined, these studies demonstrate that small structural changes of small N-containing molecules can affect their specific interactions with membrane-like interfaces, and specificity toward different membrane components.

Investigating Substrate Analogues for Mycobacterial MenJ: Truncated and Partially Saturated Menaquinones

“…The NMR samples containing the MK-1 or MK-1(H 2 ) RM solution were purged with argon briefly and capped prior to data collection. 2D NMR spectra of MK-1 and MK-1(H 2 ) in RMs were obtained using similar conditions and methods described previously 37,42,43 using a 400 MHz Varian MR400 NMR spectrometer operating at 26 °C for MK-1 and were obtained using a 500 MHz Varian Inova 500 spectrometer operating at 25 °C for MK-1(H 2 ). A standard NOESY pulse sequence was used consisting of 200 or 256 transients with either 16 or 32 scans in the f1 domain using a 200 ms mixing time, a 45°pulse angle, and a 1.5 s relaxation delay.…”

Arginine Gemini-Based Surfactants for Antimicrobial and Antibiofilm Applications: Molecular Interactions, Skin-Related Anti-Enzymatic Activity and Cytotoxicity

“…All the surfactants studied in this work have a cationic charge on the guanidine group of the arginine. In an aqueous solution, this group behaves like a weak acid; therefore, these surfactants have a weak acidic character and present an acid-base equilibrium with an associated acidity constant that depends on the pH and on a monomer–aggregate equilibrium [ 16 ].…”

“…The binding sites on the structure of collagenase, elastase and hyaluronidase were made using the Auto Grid step using the original ligands as a reference. The grid box with number points in the box (x, y, z) (16,38,16) has been chosen. All parameters were default settings using Autodock Tools 1.5.4 44.…”

The Interfacial Interactions of Glycine and Short Glycine Peptides in Model Membrane Systems

“…The pK a values were determined by plotting chemical shifts of the samples at their varying pH values in D 2 O and w 0 10 RMs and calculating the first derivative of the best fit curve using OriginPro version 9.1 [ 62 ]. In order to do this, a plot was made of ppm vs. pH and the curve was fitted in Origin using the reference described in [ 62 ] for monofunctional acids. In order to do this, half of the bifunctional curve of ppm vs. pH was plotted and a best fit line was applied.…”