Structures in solid state and solution of dimethoxy curcuminoids: regioselective bromination and chlorination.

Chemistry Central Journal (Impact Factor: 1.66). 06/2013; 7(1):107. DOI: 10.1186/1752-153X-7-107
Source: PubMed

ABSTRACT Several papers described the structure of curcumin and some other derivatives in solid and in solution. In the crystal structure of curcumin, the enol H atom is located symmetrically between both oxygen atoms of the enolone fragment with an O...O distance of 2.455 A, which is characteristic for symmetrical H-bonds. In the solution, the geometry of the enolone fragment is attributed to the inherent disorder of the local environment, which solvates one of the basic sites better than the other, stabilizing one tautomer over the other. In this paper, how the position of methoxy groups in dimethoxy curcuminoids influence the conformation of molecules and how the halogen atoms change it when they are bonded at alpha-position in keto-enol part of molecules is described.
Six isomers of dimethoxy curcuminoids were prepared. Conformations in solid state, which were determined by X-ray single crystallography and 1H MAS and 13C CPMAS NMR measurements, depend on the position of methoxy groups in curcuminoid molecules. In solution, a fast equilibrium between both keto-enol forms exists. A theoretical calculation finding shows that the position of methoxy groups changes the energy of HOMO and LUMO. An efficient protocol for the highly regioselective bromination and chlorination leading to alpha-halogenated product has been developed. All alpha-halogenated compounds are present mainly in cis keto-enol form.
The structures in solid state of dimethoxy curcuminoids depend on the position of methoxy groups. The NMR data of crystalline solid samples of 3,4-diOCH3 derivative, XRD measurements and X-ray structures lead us to the conclusion that polymorphism exists in solids. The same conclusion can be done for 3,5-diOCH3 derivative. In solution, dimethoxy curcuminoids are present in the forms that can be described as the coexistence of two equivalent tautomers being in fast equilibrium. The position of methoxy groups has a small influence on the enolic hydrogen bond. Theoretical calculations show that the energy gap between HOMO and LUMO depend on the position of methoxy groups and are lower in solution. Chlorination and bromination on alpha-position of 1,3-diketone moiety do not change the preferential form being cis keto-enol as in parent compounds.

  • Biochemical Pharmacology 09/1976; 25(15):1811-2. · 4.65 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Some pharmacological actions of curcumin (diferuloyl methane) have been examined in rats, mice and cats. The compound possesses significant anti-inflammatory activity in acute as well as in chronic models of inflammation. It is as potent as phenylbutazone in the carrageenan oedema test but only half as potent in chronic tests. Curcumin possesses a much lower ulcerogenic index than phenylbutazone. It prevents the inflammation induced increase in SGOT and SGPT levels. It lacks analgesic and antipyretic activity. It has no other significant pharmacological effects. The oral LD50 in mice is more than 2ṁ0 g kg−1.
    Journal of Pharmacy and Pharmacology 07/1973; 25(6):447-52. · 2.16 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: When activated, NF-kappa B, a ubiquitous transcription factor, binds DNA as a heterodimeric complex composed of members of the Rel/NF-kappa B family of polypeptides. Because of its intimate involvement in host defense against disease, this transcription factor is an important target for therapeutic intervention. In the present report we demonstrate that curcumin (diferuloylmethane), a known anti-inflammatory and anticarcinogenic agent, is a potent inhibitor of NF-kappa B activation. Treatment of human myeloid ML-1a cells with tumor necrosis factor (TNF) rapidly activated NF-kappa B, which consists of p50 and p65 subunits, and this activation was inhibited by curcumin. AP-1 binding factors were also found to be down-modulated by curcumin, whereas the Sp1 binding factor was unaffected. Besides TNF, curcumin also blocked phorbol ester- and hydrogen peroxide-mediated activation of NF-kappa B. The TNF-dependent phosphorylation and degradation of I kappa B alpha was not observed in curcumin-treated cells; the translocation of p65 subunit to the nucleus was inhibited at the same time. The mechanism of action of curcumin was found to be different from that of protein tyrosine phosphatase inhibitors. Our results indicate that curcumin inhibits NF-kappa B activation pathway at a step before I kappa B alpha phosphorylation but after the convergence of various stimuli.
    Journal of Biological Chemistry 11/1995; 270(42):24995-5000. · 4.60 Impact Factor

Full-text (2 Sources)

Available from
May 22, 2014