Synthesis and Characterization of Transition Metal Complexes of Chlorpromazine

The chlorpromazine (CP) complexes of the transition metal ions, Zn(II), Cd(II) and Hg(II), have been synthesized. The complexes have been characterized by their elemental analysis, molar conductivity, magnetic susceptibility, UV-Visible, IR and H-NMR data. The molecular formulations of the new mononuclear complexes have been found to be [ZnBr(C17H19ClN2S.HCl)2]Br, [CdBr(C17H19ClN2S.HCl)2]Br.H2O, [Cd(C17H19ClN2S.HCl)2]I2 and[HgBr((C17H19C lN2S.HBr)2]Br.2H2O, where the ligand chlorpromazine or CP = C17H19ClN2S. The complexes, [ZnBr(C17H19ClN2S.HCl)2]Br, [CdBr(C17H19ClN2S.HCl)2]Br.H2O, and [HgBr((C17H19ClN2S.HBr)2]Br.2H2O, behave in DMF solutions as 1:1 electrolytes while the other complex, [Cd(C17H19ClN2S.HCl)2]I2, shows an ionic ratio of 1:2 in solution. Molecular structures have been proposed showing a square pyramidal environment around each metal center with an spd hybridization for the five-coordinate complexes, [ZnBr(C17H19ClN2S.HCl)2]Br, [CdBr(C17H19ClN2S.HCl)2]Br.H2O, and [HgBr((C17H19Cl N2S.HBr)2]Br.2H2O. In the four-coordinate [Cd(C17H19ClN2S.HCl)2]I2 complex, the Cd(II) center with an sp hybridization has a tetrahedral environment around it.

distilled water was used in all preparations.

Physical Measurements
Elemental analyses of complexes were performed by Mi croanalysis Laboratory, University of Illinois, Ur bana-C hampaign, IL. Molar conductance was determined with the Conductance-Resistance meter. UV-Visible spectra were recorded on a Shimadzu UV1601 spectrophotometer. The infrared spectra were recorded on a Shimadzu FTIR 8400 spectrometer using potassium bromide pellets. 1 H-NMR spectra were recorded on a JEOL-300MHz FT-NMR spectrometer in DMSO-d 6 . Mass magnetic susceptibilities of the complexes were measured at room temperature with a Johnson Matthey magnetic susceptibility balance which uses HgCo(SCN) 4 as a calibrant.

General Synthesis of Complexes
A solution of the transition metal salt (x mmol) (ZnBr 2, CdBr 2 , CdI 2 and HgBr 2 ) dissolved in a minimum volume of MeOH was slowly added with stirring to a concentrated methanolic solution of CP.HCl (2x mmol) and refluxed overnight. Each reaction mixture was cooled overnight at 0℃ and the precipitated product isolated by suction filtration through a medium-glass fritted funnel. The product was washed with small amounts of cold water first followed by methanol, air-dried, and dried in vacuo over anhydrous CaSO 4 in a desiccator. Each crude product was recrystallized twice from a hot saturated solution of the crude sample in methanol. The yield was determined.

Results and Discussion
The elemental analysis data listed in Table 1 show that the theoretical values are in agreement with the experimental ones. Physical properties of the new metal-CP.HCl complexes are presented in Table 2. Complexes are colored, microcrystalline, and relatively stable at room temperature with percent yields ranging from 71 to 93. The complexes are slightly soluble in common polar solvents such as MeOH and readily soluble in DMF and DMSO. All complexes except Zn(II) complex are insoluble in water.
The stoichiometric reactions involved in the complex formation are represented by the equations (1) and (2) In the reaction for the formation of Hg(II) complex (eq. (2)), the larger Hg(II) ion as a soft acid tends to preferentially coordinate with the soft base Br − as compared to the relatively harder Cl − ion of the ligand. The molecular formulations and structures of the complexes were determined on the basis of elemental analysis, molar conductance, UV-Vis, IR, and NMR data.  The molar conductances for the complexes, measured in DMF and acetonitrile solutions, presented in Table 2 indicate that all complexes behave as 1:1 electrolytes (except CdI 2 complex which has 1:2 ionic ratio). Magnetic data of the complexes differ from the normal behavior of the d 10 metal ions, Zn(II), Cd(II) and Hg(II), which are probably due to impurities [20]. The molecular formulations listed in Table 1 show that each complex contains a metal center and two chlorpromazine hydrochloride molecules as principal ligands. The other ligands include bromide and iodide ions. Additionally, complexes of CdBr 2 and HgBr 2 contain one and two H 2 O molecules, respectively, as water of hydration.
Relevant IR absorption frequencies of the CP.HCl ligand and its metal complexes are presented in Table 4. In the uncomplexed CPHCl, the presence of a broad band in the 2000-2730 cm -1 range is assigned to the interaction of the quaternary ammonium ion, (R 3 NH) + ion with a halide ion [12][13][14][15]21,22]. In the IR spectra of the metal-CP.HCl complexes, this band has shifted with diminished intensity suggesting that the exocyclic N atom of the alkylamino group is indirectly involved in coordination with the metal center. A band observed in the 3000-2800 cm -1 region in the spectrum of CP.HCl may be assigned to the heterocyclic nitrogen atom carrying an alkyl amine side chain [21,22]. This band of CP.HCl shows a shift upon complexation suggesting its coordination to the metal(II) center [10][11][12][13][14]. In addition, CdBr 2 and HgBr 2 complexes show a broad band in the 3250-3560 cm -1 region, supporting the hydrogen bonded OH interactions of the water of hydration. The Hg(II) complex spectrum shows that bands in the 600-700 cm -1 and 715-740 cm -1 regions, attributable to the heterocyclic C-S-C modes, undergo a shift, suggesting heterocyclic sulfur atom as a coordination site [12,15,22]. The 1 H NMR data for the ligand, CP.HCl, and its complexes are presented in Table 5. Comparing the absorption peaks/multiplets and the chemical shifts of the uncomplexed ligand with those of corresponding complexes, it could be inferred that some of the resonance signals experience shifts upon complexation. Especially, in the free CP.HCl ligand, the broad singlet which occurs far down field (δ 10.80), attributable to the exocyclic (R 3 NH) + proton, has shifted upfield on complexation indicating a change in this proton environment. This indirectly supports the existence of intramolecular hydrogen bonding between (R 3 NH) + and Xof the MX 3 moiety [12,15,24]. Absorption of (>N-R 1 ) (cm -1 ) Absorption of (C-S-C) (cm -1 )  Crystals of sufficient quality required to permit x-ray crystallographic analysis of the complexes could not be grown. Based on the discussed analytical data, tentative square pyramidal structures have been proposed for the complexes (Fig. 2.a-2.c). Similar structures have been reported for other phenothiazine-transition metal complexes [12][13][14][15]24]. A square pyramidal geometry around each M(II) metal center (sp 3 d hybridized), due to the steric constraints of the bidentate ligand not favoring a trigonal bipyramidal arrangement, involves two CP.HCl ligands and a monodentate bromide ion. With the relatively hard acids, Zn(II) and Cd(II) (Fig. 2.a), the CP.HCl binds through its heterocyclic N atom (as a hard base) directly and through the exocyclic N atom indirectly through the H-bonding with a halide ion. The scorpion tail like N-alkylamino group with its flexible bending mode is well suited for this kind of intramolecular H-bonding in NPTZs. The two protonated (CPH + ) ligands coordinate to the MX 3 unit of the compound through two N atoms resulting in a square planar MX 2 N 2 unit, which along with an axial M-X bond represents a square-pyramidal geometry for each complex. In the [HgBr(C 17 H 19 ClN 2 S.HBr) 2 ]Br.2H 2 O complex ( Fig. 2.b), the relatively soft acid, Hg(II) binds to the CP ligand through its heterocyclic S atom (as a soft base) directly and through the exocyclic N atom indirectly through its H-bonding with a halide ion. In the [Cd(C 17 H 19 ClN 2 S.HCl) 2 ]I 2 complex (Fig.  2.c), the Cd(II) center with an sp 3 hybridization has a tetrahedral environment around it [14,15]. Similar transition metal complex structures have been reported in the literature [10][11][12][13][14][15].

Conclusions
Four transition metal-chlorpromazine complexes have been successfully prepared and characterized based on their spectroscopic data. Square-pyramidal and tetrahedral geometries have been proposed for the new complexes. The future work would be on the determination of antioxidant and free radical scavenging activities of these complexes using standard assays.