Pashkovskaya Alina A, Gumerova Nadiia I, Rompel Annette, Pohl Elena E
Physiology and Biophysics, Department of Biological Sciences and Pathobiology, University of Veterinary Medicine, Vienna, Austria.
Universität Wien, Fakultät für Chemie, Institut für Biophysikalische Chemie, Wien, Austria.
Front Chem Biol. 2024 Oct 11;3. doi: 10.3389/fchbi.2024.1454558.
Polyoxometalates (POMs) are metal-oxygen clusters composed of {MO} octahedra that have attracted considerable attention due to their remarkable antiviral, antibacterial and antitumor activities. Despite their potential, the molecular mechanisms underlying their cellular toxicity remain poorly understood. This study investigates how Anderson-Evans type polyoxotungstates (POTs) and polyoxomolybdates (POMos) interact with biological membranes by examining their effects on the zeta (ζ) - potential of the lipid bilayer and the size of small unilamellar liposomes of different phospholipid compositions. POTs affected the ζ-potential of neutral (1,2-dioleoyl-sn-glycero-3-phosphocholine, DOPC) and slightly negatively charged (1,2-dioleoyl-sn-glycero-3-phosphoethanolamine; DOPC:DOPE) membranes in the order [MnWO] > [Ni(OH)WO] > [TeWO]. The addition of negatively charged cardiolipin (CL) to DOPC reduced the interaction of POTs with the membrane. An opposite effect was observed for POMos, which changed the ζ-potential of neutral and slightly negatively charged membranes in the order [Al(OH)MoO] > [Cr(OH)MoO] >> [Ni(OH)MoO]. The addition of POMos increased the size of the liposomes in reverse order. The binding of [Al(OH)MoO] to the PE-containing phospholipid membranes and the effect of ionic strength on the interaction of [Cr(OH)MoO] with DOPC:CL liposomes could be inhibited by potassium fluoride (KF). Interestingly, KF did not inhibit the interaction of other POMos with membranes as indicated by ζ-potential measurements. These results suggest that the interaction of Anderson-Evans type POMs with phospholipid membranes is influenced more by their addenda and central ions than by their total charge. By unravelling the structure-activity relationships for the different POMs, we contribute to the design of biologically active POMs for therapeutic use.
多金属氧酸盐（POMs）是由{MO}八面体组成的金属 - 氧簇，因其显著的抗病毒、抗菌和抗肿瘤活性而备受关注。尽管它们具有潜在应用价值，但其细胞毒性的分子机制仍知之甚少。本研究通过考察Anderson - Evans型多金属钨酸盐（POTs）和多金属钼酸盐（POMos）对脂质双层的zeta（ζ）电位以及不同磷脂组成的小单层脂质体大小的影响，来研究它们与生物膜的相互作用。POTs对中性（1,2 - 二油酰 - sn - 甘油 - 3 - 磷酸胆碱，DOPC）和略带负电荷（1,2 - 二油酰 - sn - 甘油 - 3 - 磷酸乙醇胺；DOPC:DOPE）膜的ζ电位影响顺序为[MnWO] > [Ni(OH)WO] > [TeWO]。向DOPC中添加带负电荷的心磷脂（CL）会降低POTs与膜的相互作用。对于POMos则观察到相反的效果，其对中性和略带负电荷膜的ζ电位影响顺序为[Al(OH)MoO] > [Cr(OH)MoO] >> [Ni(OH)MoO]。添加POMos会使脂质体大小按相反顺序增加。[Al(OH)MoO]与含PE的磷脂膜的结合以及离子强度对[Cr(OH)MoO]与DOPC:CL脂质体相互作用的影响可被氟化钾（KF）抑制。有趣的是，如ζ电位测量所示，KF并未抑制其他POMos与膜的相互作用。这些结果表明，Anderson - Evans型POMs与磷脂膜的相互作用更多地受其附加原子和中心离子影响，而非总电荷。通过揭示不同POMs的构效关系，我们有助于设计用于治疗的生物活性POMs。
