Synthesis, and electrochemical and density functional studies of new copper(II)- and manganese(II) -oxicam drugs. Redox potentials and MOs compatible with SOD-like activity and unusual six-membered rings of water molecules bridging complex units

The synthesis and rare structures of Mn-II and Cu-II complexes with OXI drugs (oxicam, a family of non-steroidal anti-inflammatory drugs) are reported. On mixing Mn-II acetate with piroxicam (H2PIR) pale yellow single crystals of trans,trans-[Mn-II(O-N,N-DMF)(2)(N,O-HPIR)(2)], 1, dimethylformamide (DMF), were obtained. The structure shows two HPIR- anions chelate through pyridyl nitrogen and amide oxygen, and two positions around the metal atom are occupied by the two DMF molecules. The Mn-O(amide, HPIR) vector is much shorter than the two other coordination vectors, a novelty for M-II(L)(2)(HOXI)(2) molecules. Single crystals of trans,trans-[Cu-II(H2O)(2)(N,O-HTEN)(2)]center dot 4H(2)O center dot 2DMF, 2, (H2TEN, tenoxicam,) were obtained by long storage from DMF solutions of Cu-II(HTEN)(2) during loading smart synthetic hydrogels. Compound 2 is the first example for M-II(HOXI)(2) units, linked to H2O molecules ever reported, and extensive networks of H2O center dot center dot center dot OH2 hydrogen bonds and Cu center dot center dot center dot OH2 bonds that involve six member cycles of water molecules arranged as puckered rings bridging M-II(HOXI)(2) entities. Infrared bands related to amide groups for HOXI- ligands are significantly influenced by the strength of M-O bonds in agreement with bond length trends. Electrochemical studies for Cu-II(HTEN)(2) in tetrahydrofuran are in agreement with a SOD-like scavenger activity at least for superoxide oxidation to molecular oxygen, E degrees(Cu-II/Cu-I, SCE) -0.31V. Furthermore, density functional investigation at the gas phase reproduces well the structure for trans,trans-[Mn-II(O-DMF)(2)(N,O-HPIR)(2)] sextuplet molecule and for trans,trans-[Cu-II(H2O)(2)(N,O-HTEN)(2)] doublet molecule. Even a model of the {Cu-II(HTEN)(2)(OH2)center dot center dot center dot(H2O)(4)center dot center dot center dot(H2O)Cu-II(HTEN)(2)} entity found for 2 is well reproduced by theory. The estimate stabilization energy brought about by the six water molecules ring between two Cu-II(HTEN)(2) molecules is 69 kcal