NMR Study Directly Determining Drug Delivery Sites in Phospholipid Bilayer Membranes

Abstract

The drug delivery (DD) process of benzene derivatives, n-propylbenzene (PrBe) and benzyl alcohol (BzOH), from water to phospholipid vesicles is first monitored by noninvasive NMR technique. The bilayer interface and interior as delivery sites are unambiguously specified by taking advantage of the site selectivity of NMR. Chemical shift differences of the ring proton signals provide direct evidence for the penetration of the "drugs" into the bilayer within a few minutes. PrBe is deeply penetrated into the hydrophobic chain region of the bilayer core. In contrast, BzOH is preferentially trapped in the interfacial region near the carbonyl group of the phospholipid, with the methylene group oriented toward the inside of the bilayer. The delivery site of BzOH is characterized by the doublet of the ring proton NMR signal, which is ascribed to BzOH delivered into the outer and inner layers of the vesicle. This is also confirmed by 13 C NMR, for the first time applied to specify the delivery site. UV absorption spectra of PrBe and BzOH in vesicles are consistent with the delivery sites determined by NMR. Application of the molecular level study of the DD processes to recent severe problems of endocrine disruptors (EDs) is finally proposed as a basis for the comprehensive understanding of the molecular mechanism of the membrane disrupting action and for the purpose of detoxication and the prevention of ED accumulation.

Raman spectroscopy of model membrane monolayers of dipalmitoylphosphatidic acid at the air-water interface using surface enhancement from buoyant thin silver films

“…Studies of phospholipid films in dispersions, Langmuir layers, and Langmuir–Blodgett layers are well documented as biological membrane models 1. These assemblies have been studied by a wide range of techniques including NMR spectroscopy,2–14 X‐ray and electron diffraction,15–17 fluorescence spectroscopy,18–32 optical and spectroscopic microscopy,20, 22, 24, 33 scanning probe microscopies,34–37 and the vibrational spectroscopies FTIR,38–51 Raman,42, 52–63 and vibrational sum‐frequency generation 64–66. The vibrational spectroscopies provide much needed data about molecular structure and interactions between lipid molecules in such assemblies, particularly for the alkyl chain.…”

Limited Slowdown of Endocrine-Disruptor Diffusion in Confined Fluid Lipid Membranes

“…Attention is also paid to the relation of the BPA mobility to the location in membrane previously determined by the static NMR analysis [11,12]. To ensure the site dependence of drug dynamics in membranes, we identify the location and the mobility of benzene and toluene in membrane and compare them with the case of BPA (hereafter, benzene and toluene are also called a ''drug'').…”

Mobility and location of anesthetics in lipid bilayer membranes by high-resolution, high-field-gradient NMR

“…The high-resolution natural-abundance 13 C NMR method can distinguish the individual carbon atom site of the bilayer without labeling [2][3][4][5][6]. Utilizing the site-selective 13 C NMR, we specify the preferential location of anesthetics in membranes at the molecular level.…”