In First Time: Synthesis and Spectroscopic Interpretations of Manganese(Ⅱ), Nickel(Ⅱ) and Mercury(Ⅱ) Clidinium Bromide Drug Complexes

Samy M. El-Megharbel; Moamen S. Refat

doi:10.3964/j.issn.1000-0593(2021)10-3316-05

Clidinium is a synthetic anticholinergic agent which has been shown in experimental and clinical studies to have an antispasmodic and antisecretory effect on the gastrointestinal tract. Inhibits the muscarinic effects of acetylcholine at neurotransmitter sites after parasympathetic ganglia. It is used to treat peptic ulcer disease and to help relieve stomach or stomach cramps or cramps due to abdominal cramps, diverticulitis, and irritable bowel syndrome. Mononuclear complexes of the manganese(Ⅱ), nickel(Ⅱ) and mercury(Ⅱ) with clidinium bromide drug (C₂₂H₂₆NO₃) types [M(C₂₂H₂₅NO₃)₂(H₂O)₄] and [Hg(C₂₂H₂₅NO₃)₂(H₂O)₂] where M=Mn (Ⅱ) and Ni(Ⅱ), have been synthesized and characterized on the basis of elemental analysis, conductivity measurements, magnetic, electronic, ¹H-NMR and infrared spectral studies. The complexes confirm to 1:2 stoichiometry and are non-electrolytes. The clidinium drug ligand (C₂₂H₂₆NO₃) act as a deprotonated monovalent monodentate chelate coordinating through hydroxyl oxygen where IR spectral bands of clidinium bromide shows a band at 3 226 cm^-1 assigned to the OH group stretching frequency, this band ν(O—H) stretching vibration motion is disappeared in case of the infrared spectra of the Mn(Ⅱ), Ni(Ⅱ), and Hg(Ⅱ) complexes suggesting the involvement of the oxygen atom of the deprotonated OH group of clidinium ligand in complexation. The band for the ν(C—O) of alcoholic group of clidinium that appears at 1 240 cm^-1 has blue shifted after complexity, indicating the participation of the alcoholic group in the coordination . ¹H NMR spectrum for clidinium bromide show a singlet peak at 3.65 ppm due to proton of OH group which isn’t observed in the spectrum of mercury(Ⅱ) complex referring to the deprotonation of OH group and participated in the complexation. Based on electronic spectra, IR spectra and magnetic moment measurements; six coordinated octahedral structures have been proposed for the manganese and nickel(Ⅱ) complexes, while mercury(Ⅱ) complex has a four coordinated geometry. Thermogravimetric analyses studies revealed the presence of coordinated water molecules. For instance the X-ray powder diffraction pattern and scanning electronic microscopy for the Hg(Ⅱ) complex deduced that it was isolated in nanostructured with crystallinity form.

Clidinium bromide is an anticholinergic drug which may help symptoms of cramping and abdominal stomach pain by decreasing stomach acid and slowing the intestines. It is commonly prescribed in combination with chlordiazepoxide by the name of clidinium-c^[1]. Accurate, simple, and selective stability-indicating reversed phase HPLC and TLC-densitometric methods with UV detection have been developed and validated for simultaneous determination of chlordiazepoxide and clidinium bromide in the presence of its alkaline induced degradation product. Successful separation of the drugs from the degradation product was achieved^[1]. The spectroscopic and structural morphology properties of the charge transfer complex of the anticholinergic drug clidinium bromide with picric acid have been studied^[2] in three polar solvents acetonitrile, methanol, and ethanol at room temperature. The formed transfer complex complex in each solvent was characterized in both solution and solid state using electronic, IR, and ¹H and ¹³CNMR spectroscopies and XRD, SEM, TEM, and CHN elemental analyses. The outcome suggests that the formation of the CT complex is high in less polar solvent and that its spectroscopic and morphologic characteristics are markedly affected by the variation in solvent polarity. The United States Pharmacopeia (USP) stated the nonaqueous titration method for the assay of clidinium bromide and chlordiazepoxide^[3,4,5,6]. Few methods for the determination of clidinium bromide and chlordiazepoxide in combined dosage forms including HPLC^[7,8,9], derivative spectrophotometry^[10,11], spectrophotometry using multivariate calibration techniques^[12], and capillary SFC^[13] have been reported. The present article reports studies on interactions between clidinium bromide drug and some of divalent transition metal ions like (Mn(Ⅱ), Ni(Ⅱ), and Hg(Ⅱ)). The elemental analysis, conductivity, IR and, ¹H-NMR, electronic spectral studies of these complexes were assignments and deduced the suggested structure via deprotonation of the hydroxyl —OH group.