Molecular motion in chlorpromazine and chlorpromazine hydrochloride

Abstract

Chlorpromazine, I, and chlorpromazine hydrochloride, II, have been studied in the solid state with pulsed NMR techniques. The relaxation times, TV, Tlp, and T1D, and second moments, M2, have been measured from 98 K to the melting point of the solid. Methyl reorientation was observed in both compounds with activation barriers of 2.5 and 2.0 kcal/mol, respectively. The onset of a second motion in I is observed in the high temperature region with an activation barrier of 3.9 kcal/mol. The M2 transition associated with this motion is very large, which suggests that it involves motion of the aminopropyl chain. The motion is attributed to the fact that the chain configuration is trans-gauche and a model for the motion is discussed. A phase transition occurs in II in the high temperature region.

Electrochemically Induced Mesomorphism Switching in a Chlorpromazine Hydrochloride Lyotropic Liquid Crystal

“…This is in agreement with literature studies on the influence of self-assembly on redox properties. − Accordingly, we suggest this reflects the additional energy required to separate aggregated molecules, owing to both the increased charge and the “butterfly-shaped”-to-planar transition that occurs on oxidation, which is manifested through an intrinsic activation barrier . Given that ring inversion in dilute solutions of chlorpromazine is considered to be rapid, even at low temperature, , we thus suggest that these data are consistent with conformational change occurring in concert with electron transfer.…”

“…The tranquilizing drug, chlorpromazine (Figure a), and its derivatives are often used as one-electron mediators in electrochemistry, as well as in the treatment of schizophrenia; its biological activity is thought to derive from its facile oxidation and photo-oxidation to a stable cation radical − and its flexibility: − in the solid state and in solution, the neutral molecule folds about the N–S axis with the central six-ring in a boat confirmation (“butterfly”-shaped, dihedral angle of 139–153°, Figure a), with rapid molecular motions that include those associated with the side chain, pyramidal inversion at nitrogen and ring inversion, even at low temperatures . Oxidation to the cation radical flattens the ring system through relaxing steric repulsions and readjusting the side chain, so that the dihedral angle opens up to 170–180°. − In contrast, further oxidation to the dication followed by hydrolysis with water yields the corresponding sulfoxide, which is thought to exist with the central six-ring in the boat conformation, at least in the solid state . Accordingly, the conformational change on oxidation to the cation radical affords a bathochromic shift in the absorption: slightly yellow chlorpromazine ,, (white as the hydrochloride on the side chain, ,, p K BH + = 9.15–9.3) converts to the pink cation radical , (λ max = 526–534, 775–865 nm); the sulfoxide is known to be red .…”

Direct Observation of Hole Shift and Characterization of Spin States in Radical Ion Pairs Generated from Photoinduced Electron Transfer of (Phenothiazine)n–Anthraquinone (n = 1, 3) Dyads

“…The rate constant of phenyl rotation in 10-phenylphenothiazine has not been determined experimentally, although dynamic NMR of phenothiazine derivatives at low temperatures has been conducted. 42, 43 The observed hole-shift process (τ hole-shift = 6 ns) in the present study can serve as an upper limit in the time constant for phenyl rotation in 10-phenylphenothiazines.…”

“…The rate of rotation of the phenyl ring in 10-phenylphenothiazine should be much faster than that of 10-phenylanthracene because the steric repulsions between the ortho protons in the phenyl group and the peri-positioned protons in the phenothiazine can be quite diminished by the pyramidalization of the nitrogen atom. The rate constant of phenyl rotation in 10-phenylphenothiazine has not been determined experimentally, although dynamic NMR of phenothiazine derivatives at low temperatures has been conducted. , The observed hole-shift process (τ hole‑shift = 6 ns) in the present study can serve as an upper limit in the time constant for phenyl rotation in 10-phenylphenothiazines.…”