Trapping and reversing neuromuscular blocking agent by anionic pillar[5]arenes: Understanding the structure-affinity-reversal effects.
J Hazard Mater
; 469: 133875, 2024 May 05.
Article
en En
| MEDLINE
| ID: mdl-38457970
ABSTRACT
Selective relaxant binding agents (SRBA) have great potential in clinical surgeries for the precise reversal of neuromuscular blockades. Understanding the relationship between the structure-affinity-reversal effects of SRBA and neuromuscular blockade is crucial for the design of new SRBAs, which has rarely been explored. Seven anionic pillar[5]arenes (AP5As) with different aliphatic chains and anionic groups at both edges were designed. Their binding affinities to the neuromuscular blocking agent decamonium bromide (DMBr) were investigated using 1H NMR, isothermal titration calorimetry (ITC), and theoretical calculations. The results indicate that the capture of DMBr by AP5As is primarily driven by electrostatic interactions, ion-dipole interactions and C-Hâ§â§â§π interactions. The optimal size matching between the carboxylate AP5As and DMBr was â¼0.80. The binding affinity increased with an increase in the charge quantity of AP5As. Further animal experiments indicated that the reversal efficiency increased with increasing binding affinity for carboxylate or phosphonate AP5As. However, phosphonate AP5As exhibited lower reversal efficiencies than carboxylate AP5As, despite having stronger affinities with DMBr. By understanding the structure-affinity-reversal relationships, this study provides valuable insights into the design of innovative SRBAs for reversing neuromuscular blockade.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Fármacos Neuromusculares no Despolarizantes
/
Gamma-Ciclodextrinas
/
Organofosfonatos
/
Bloqueantes Neuromusculares
Límite:
Animals
Idioma:
En
Revista:
J Hazard Mater
Asunto de la revista:
SAUDE AMBIENTAL
Año:
2024
Tipo del documento:
Article
País de afiliación:
China