13C NMR studies of the molecular dynamics of chlorpromazine in solution

Sakamoto, Yohko; Ishii, Tomoko; Kurokawa, Noriko; Aoki, Toshikazu; Ohshima, Shigeru

doi:10.1016/0022-2860(95)09082-7

Cited by 1 publication

(2 citation statements)

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“…Reports in the literature suggest that this conformation should correlate with biological activity. 49 The partial atomic charges were obtained through a single point HF/6-31G* calculated with ChelpG. 50 No parameters are available in the literature for this molecule and, therefore, we based our parametrization, including intramolecular bond lengths and angles, on the equilibrium geometry just described.…”

Section: Structuring Of Cpz Interacting With the Dppc Monolayermentioning

confidence: 99%

“…The calculated CPZ geometry is in fairly good agreement with the structure determined by X-ray diffraction, with a bent structure in which the side chain of CPZ tilts toward the chlorinated benzene ring. Reports in the literature suggest that this conformation should correlate with biological activity . The partial atomic charges were obtained through a single point HF/6-31G* calculated with ChelpG .…”

Section: Structuring Of Cpz Interacting With the Dppc Monolayermentioning

confidence: 99%

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Molecular Dynamics Simulations of Neutral Chlorpromazine in Zwitterionic Phospholipid Monolayers

2006

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Molecular dynamics simulations have been performed to investigate the interactions between chlorpromazine (CPZ), a neuroleptic drug used in the treatment of psychiatric disorders, and dipalmitoylphosphatidylcholine (DPPC), a zwitterionic phospholipid, in Langmuir monolayers. The results from simulations carried out at different monolayer surface densities were able to capture important features of the CPZ-lipid interaction. We find that neutral (unprotonated) CPZ is preferentially located in the lipid tail region of the phospholipids, in little contact with the aqueous phase, and that the orientation of its rigid ring structure and tail conformation vary with lipid surface density. CPZ is found to promote ordering of the lipid tails for all surface densities because of a reduction in the effective surface area per lipid upon addition of the drug. Similar effects have been observed in previous studies of cholesterol in DPPC monolayers, in which lipid tails were seen to order around the solute. This feature, however, is quite distinct from what we observe for the most dense monolayer considered here (area per lipid of 50 A(2)), for which we find that CPZ promotes a local distortion of the lipid tails in its immediate vicinity and a concomitant ordering of lipid tails located further away from the solute. This view is further supported by the results obtained for an approximated nonlinear vibrational sum frequency generation susceptibility, which showed greater tail disorder close to CPZ.

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Section: Structuring Of Cpz Interacting With the Dppc Monolayermentioning

confidence: 99%

Section: Structuring Of Cpz Interacting With the Dppc Monolayermentioning

confidence: 99%