Warfarin is a coumarin derivative drug widely used for its anticoagulant properties. The interaction of warfarin with fully hydrated lipid bilayers has been studied by combining differential scanning calorimetry, spectrophotometry, electron spin resonance of chain-labelled lipids and molecular docking. Bilayers formed by lipids with different chemico-physical properties were considered, namely dimyristoyl-phosphatidylcholine (DMPC), dimyristoyl-phosphatidylglycerol (DMPG), and dioleoyltrimethyl-ammoniumpropane (DOTAP). We observed in all cases the binding of warfarin in proximity of the surface of the bilayers, leading to a variety of distinct effects on key molecular properties of the membranes. The drug associates with the lipid bilayers in the deprotonated open chain form, with an association constant similar for DMPC and DMPG (1.27·10⁴ and 2.82·10⁴ M⁻¹, respectively) and lower for DOTAP (0.46·10⁴ M⁻¹). In DMPC bilayers, which are zwitterionic and with saturated symmetrical chains, warfarin at 10 mol% suppresses the pre-transition, slightly stabilizes the fluid state and reduces the cooperativity of the main transition. Moreover, it alters the lateral packing density of the chain segments close to the polar/apolar interface at any temperature through the gel phase. In anionic DMPG bilayers, the drug slightly perturbs the thermotropic phase behavior, and at 10 mol% markedly loosens the compact gel phase packing of the first chain segments. In cationic DOTAP bilayers, possessing unsaturated acyl chains, the drug induces a slightly higher degree of order and motional restriction in the outer hydrocarbon region in the frozen state. In all cases, as a surface adsorbed molecule, warfarin does not affect the segmental chain order and dynamics for temperatures in the fluid phase. The overall results provide an outline of the action of warfarin on membranes formed by lipids of different types.

华法林是一种香豆素衍生药物，因其抗凝特性而被广泛使用。通过组合差示扫描量热法，分光光度法，链标记脂质的电子自旋共振和分子对接，研究了华法林与完全水合脂质双层的相互作用。考虑了由具有不同化学物理性质的脂质形成的双层，即二肉豆蔻酰基磷脂酰胆碱（DMPC），二肉豆蔻酰基磷脂酰甘油（DMPG）和二油酰基三甲基铵丙烷（DOTAP）。我们在所有情况下都观察到了华法林在双层表面附近的结合，从而导致对膜的关键分子特性的各种不同影响。该药物以去质子化的开链形式与脂质双层缔合，缔合常数与DMPC和DMPG相似（1.27·10对于DOTAP分别为⁴和2.82·10 ⁴  M ^-1）和更低（0.46·10 ⁴  M ^-1）。在两性离子且具有饱和对称链的DMPC双层中，华法林的含量为10 mol％时会抑制预过渡，略微稳定流体状态并降低主过渡的协同作用。而且，它在任何温度下通过凝胶相都会改变靠近极性/非极性界面的链段的侧向堆积密度。在阴离子DMPG双层中，药物会稍微扰乱热致相的行为，在10 mol％时，该药物会明显松散第一链段的紧密凝胶相堆积。在具有不饱和酰基链的阳离子DOTAP双层中，药物在冷冻状态下在外部烃区域中诱导略高的有序度和运动限制。在所有情况下，作为表面吸附分子，华法林不影响流体相中温度的分段链顺序和动力学。总体结果概述了华法林对不同类型脂质形成的膜的作用。