TY - JOUR
T1 - Binding of cis-[Ru(phen)2(3,4Apy)2]2+ to Model Lipid Membranes
T2 - Implications for New Tools in the Development of Antiamyloid Drugs
AU - da Cruz Garcia, Maria Laura
AU - Paixão, Rafaela Ribeiro
AU - Pazin, Wallance M.
AU - Oliveira, Osvaldo N.
AU - Cremer, Paul S.
AU - Carlos, Rose Maria
N1 - Publisher Copyright:
© 2024 The Authors.
PY - 2024/12/31
Y1 - 2024/12/31
N2 - This study explores the interactions of the cis-[Ru(phen)2(Apy)2]2+ complex (RuApy, phen = 1,10-phenanthroline, Apy = 3,4-aminopyridine) with model lipid membranes to explain the role this complex plays in mitigating Aβ toxicity in PC12 neuronal cells. Fluorescence quenching, surface pressure isotherms in Langmuir monolayers, and infrared reflection-absorption analyses revealed that the positively charged RuApy interacts with the phosphate headgroups of monolayers, indirectly affecting ester carbonyl groups through hydrogen bonding with the amino group of the pyridine ligand of RuApy. These results offer a scenario for the protective effect of RuApy against Aβ toxicity in neuronal cells in which these interactions shield the electrostatic interactions of Aβ with lipid membranes, preserving membrane integrity and mitigating the deleterious influence of Aβ. This opens new avenues for antiamyloid strategies, focusing on compounds that prevent salt-bridge formation between bilayer membranes and amyloid proteins, aiding in the rational design of effective antiamyloid agents for therapeutic application.
AB - This study explores the interactions of the cis-[Ru(phen)2(Apy)2]2+ complex (RuApy, phen = 1,10-phenanthroline, Apy = 3,4-aminopyridine) with model lipid membranes to explain the role this complex plays in mitigating Aβ toxicity in PC12 neuronal cells. Fluorescence quenching, surface pressure isotherms in Langmuir monolayers, and infrared reflection-absorption analyses revealed that the positively charged RuApy interacts with the phosphate headgroups of monolayers, indirectly affecting ester carbonyl groups through hydrogen bonding with the amino group of the pyridine ligand of RuApy. These results offer a scenario for the protective effect of RuApy against Aβ toxicity in neuronal cells in which these interactions shield the electrostatic interactions of Aβ with lipid membranes, preserving membrane integrity and mitigating the deleterious influence of Aβ. This opens new avenues for antiamyloid strategies, focusing on compounds that prevent salt-bridge formation between bilayer membranes and amyloid proteins, aiding in the rational design of effective antiamyloid agents for therapeutic application.
UR - https://www.scopus.com/pages/publications/85212438772
UR - https://www.scopus.com/pages/publications/85212438772#tab=citedBy
U2 - 10.1021/acs.langmuir.4c03552
DO - 10.1021/acs.langmuir.4c03552
M3 - Article
C2 - 39682054
AN - SCOPUS:85212438772
SN - 0743-7463
VL - 40
SP - 27345
EP - 27355
JO - Langmuir
JF - Langmuir
IS - 52
ER -