.png){kind=icon}
.png){kind=icon}
Return
Electric field modulation of reactivity of the nitrogen mustard anticancer drug melphalan: A DFT study on aziridinium ion formation
.png){kind=icon}
PRE
AI
C
A
P
D
DOI：10.1016/j.comptc.2026.115783.png)
.png){kind=icon}
Original request for help.png){kind=icon}
Share.png){kind=icon}
Save
Abstract
En 中文
Density functional theory calculations at the omega B97X-D/SMD level were performed for aziridinium-ion formation for the anticancer drug melphalan, the key activation step of the nitrogen-mustard drug under positive and negative external electric fields (EEF) applied along a Cartesian axis. Local electronic responses were characterized using Wiberg bond indices, NBO donor-acceptor interactions, and electron localization function/localized orbital locator (ELF/LOL) descriptors. Positive fields enhance the nN ->sigma*C-Cl interaction, weaken the C-Cl bond, and shift the electron density toward a more dissociated C-Cl environment, demonstrating promotion of aziridinium formation at the electronic-structure level, while negative fields suppress these effects, slowing reactivity to reduce off-target toxicity. In contrast, the activation free energy displays a non-monotonic dependence on field strength. Analysis of field-dependent dipole moments for the reactant and transition state shows that this behavior originates from global field-induced molecular reorientation: the projections of their dipoles onto the fixed Cartesian field direction vary irregularly, leading to a non-linear relative stabilization of the transition state.
Keywords:
Nitrogen mustard chemotherapeutics
Aziridinium ion formation
Density functional theory
Electrochemotherapy
External electric field
Journal
IF:
2.8
Papers:
771
Citations:
7.2K
Organization
Cited Papers