Structural and Spectroscopic Properties of Two New Isostructural Complexes of Lapacholate with Cobalt and Copper

1 Facultad de Ciencias Exactas, Universidad Nacional de Salta, Avenida Bolivia 5150, 4400 Salta, Argentina 2 Facultad de Bioquı́mica, Quı́mica y Farmacia, Universidad Nacional de Tucumán, Ayacucho 491, 4000 Tucumán, Argentina 3 Departamento de Fı́sica, Facultad de Ciencias Exactas, Universidad Nacional de La Plata and Institute IFLP (CONICET-CCT La Plata), C. C. 67, 1900 La Plata, Argentina 4 Instituto de Fı́sica de São Carlos, Universidade de São Paulo, C.P. 369, 13560 São Carlos, SP, Brazil


Introduction
Lapachol (LapH), [2-hydroxy-3(3-methyl-2-butenyl)-1,4naphthoquinone] is a yellow pigment present in several plant species, including the Lapacho tree Tabebuia ipe (shredded wood) from which it is extracted.This extract is also used as alternative medicine for different illness such as cancer, Chagas, and various skin diseases [1][2][3][4][5][6].A tea extract from the inner bark of the Lapacho tree has been used as a folk remedy against many diseases in South America since the time of the Incas [7].Lapachol presents pharmacological activity similar to acetonaphthonates, flavonates, and hydroxypyronates [8].Several patents involving pharmaceutical applications of Lapachol have been filed in the last few years; for example, in 2008 alone there were granted 13 related patents [7].The quest for improving this activity prompted renewed work during the last 10 years on the synthesis, physicochemical characterization, and pharmacological properties of Lapachol complexes with transition metal ions, including the Zn, Ni, and Mn lapacholates [7,9,10].
In alkaline medium, LapH loses a proton.This gives rise to a lapacholate anion (Lap) and turns into a bidentate ligand (Lap) to divalent metal ions through its phenolic and quinonic oxygen atoms located at positions 1 and 2 (see Scheme 1).
We present here the synthesis, characterization and the crystal structure of two new isostructural complexes of Co(II) and Cu(II) with LapH and DMF as ligands of formula [M(Lap) 2 (DMF) 2 ], M: Co, Cu.

Preparation
Co Complex.This compound was prepared at room temperature, by mixing 0.99 g of Lapachol in 50 mL of dimethylformamide (DMF), solution of concentration 0.08 M, with 0.74 g of cobalt(II) acetate tetrahydrate in 100 mL of water (0.03 M).The precipitate, with a yield of 78.6%, was separated by filtration, washed with water, dried, and redissolved in dimethylformamide.Single crystals adequate for structural X-ray diffraction were obtained by slow evaporation of the solvent.
Cu Complex.0.54 g of Lapachol in 20 mL of DMF (0.1 M) was added to a hot (60 • C) solution of 0.56 g of copper(II) acetate in 50 mL of water (0,06 M).The resulting solution was stirred and kept at 60 • C during few minutes and then left at room temperature.The precipitate obtained, with a yield of 64.9%, was filtered out from the solution which was then allowed to evaporate until the appearance of single crystals.These were separated by filtration, washed with water, and then dried.
Lapachol was extracted with chloroform from the sawdust of "Lapacho" (Tabebuia ipé) and purified with absolute alcohol.

X-ray Diffraction
Data.The X-ray measurements were performed on an Enraf-Nonius Kappa-CCD diffractometer with graphite-monochromated MoKα (λ = 0.71073 Å) radiation.Diffraction data were collected (ϕ and ω scans with κ-offsets) with COLLECT [11].Integration, scaling, and reduction of the diffraction intensities were performed with HKL DENZO-SCALEPACK [12] suite of programs.The data for the Co complex were corrected numerically for absorption effects with PLATON [13].No absorption correction was applied to the Cu complex as the linear absorption coefficient times the largest crystal size was 0.116.The unit cell parameters were obtained by least-squares refinement based on the angular settings for all collected reflections using HKL SCALEPACK [12].The structures were solved by direct methods with SHELXS-97 [14] and the molecular model refined by full-matrix least-squares procedure on F 2 with SHELXL-97 [15].The H-atoms were positioned stereochemically and refined with the riding model.The locations of methyl hydrogen atoms were optimized during the refinement procedure by treating them as rigid bodies which were allowed to rotate around the corresponding C-C bond.Crystal data and refinement results are summarized in Table 1.Full crystal structure data have been deposited at the Cambridge Crystallographic Data Centre under reference codes CCDC 846042 (Co complex) and CCDC 846043 (Cu complex).Enquiries for data can be directed to: Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge, UK, CB2 1EZ or (e-mail) deposit@ccdc.cam.ac.uk or (fax) +44 (0) 1223 336033.

Spectra.
Infrared transmittance spectra from 4000 to 400 cm −1 region were collected at a resolution of 4 cm −1 on KBr-sandwiched samples with a Perkin Elmer GX FT-IR instrument.The electronic spectra (UV-Vis) of both solutions of DMF samples were run on a double-beam GBC 918 spectrophotometer.

Thermogravimetric Analysis.
TGA was performed under flowing oxygen (50 mL/min) with a Shimadzu TGA-50 instrument at a heating rate of 5 • C/min from room temperature to 500 • C.

Physical Properties.
The dark red crystals of both complexes were stable in ambient conditions.They are soluble in DMF, ethanol, and ether, less soluble in benzene, and insoluble in water.

Structural
Results.An ORTEP [16] drawing of the copper complex is shown in Figure 1, and corresponding bond distances and angles around the metal ion for both complexes are in Table 2.The metal ions are sited on a crystallographic inversion center in a distorted octahedral environment, equatorially coordinated to two symmetry-related lapacholate anions acting as bidentate ligands through their The molecular structure of M(Lap) 2 (DMF) 2 (M: Co, Cu) is closely related to other metal complexes with a pair of equatorially coordinated lapacholate ions.These include the Zn(Lap) 2 (EtOH) 2 center symmetric complex, where the EtOH ligands coordinate axially to the metal [9] and also Ni(Lap) 2 (DMF)(H 2 O) where two nearly parallel lapacholate ions cis-coordinate the Ni(II) ion and the octahedral axial positions are occupied by DMF and water molecules [10].The versatility of lapacholate anions to coordinate transition metal ions is shown by the related M(Lap) 2 (DMF)(H 2 O), M: Co, Zn isostructural complexes.Here the M(II) ion is also in a distorted octahedral environment, but now coordinated by two nearly orthogonal (cis) lapacholate anions with DMF and water molecules completing the octahedral coordination at cis-positions to each other [3].A similar cis coordination of near perpendicular lapacholates to metal is observed in the Cu(Lap)2bpy, where the bipyridine molecule bridges the remaining cis-positions acting as a bidentate ligand though their N-atoms [17].Also [Mn(Lap) 2 ] n shows near cis orthogonal lapacholate ions acting as bidentate ligands to Mn(II) ion through the orthocarbonyl and phenol oxygen atoms, but here the distorted octahedral coordination around the metal is completed by the para carbonyl oxygen of two neighboring complexes, giving rise to a polymeric arrangement in the lattice [7].

IR Spectra.
The IR spectra of Figure 2 show that both complexes exhibit the same transmittance profile as others studied complexes of lapacholate [10,18].The broadband centered at 3369 cm −1 (Co) and 3448 cm −1 (Cu) indicates the presence of moisture in the KBr disk that supports the .sample and therefore it will not be further discussed.In the 2800-3000 cm −1 spectral range there appear bands due  to CH stretching of the CH-CH, CH 2 , and CH 3 groups.
The stretching mode of noncoordinated to metal C8-O3 group appears at 1585 cm −1 (Co) and 1582 cm −1 (Cu), and stretching mode of the quinonic CO group (C1-O1) coordinated to the metal appears at 1630 cm −1 (Co) and 1621 cm −1 (Cu).These bands are red-shifted with respect to the corresponding bands of uncomplexed lapachol [19] at 1660 and 1640 cm −1 , upon coordination to the metal and the resonance between the para-and orthonaphthoquinone forms that involves those carbonyl groups and the noncoordinated, C8-O3, hydrogen bonded (shifts from 1640 to 1585 and 1582 cm −1 , resp.).In the region between 1620 and 1660 cm −1 , overlapping bands appear that can be assigned to CO and DMF stretching modes [20].The bands located at 1542 and 1545 cm −1 correspond to the quinone ring C-C stretching mode [18].Medium intensity bands between 1339 and 1370 cm −1 can be assigned to the DMF CN stretching, overlapping with the CH absorption of lapachol side chain [21].Bands in the 1276-1275 cm −1 range are attributed by Sawhney and Matta [22] to lapachol C10-O2 (single bond, phenol) stretching modes, but it is not possible to make definitive assignments as there may also appear overlapping in-plane CC and CH coupled vibrations [22,23].The M-O stretching modes are expected in the region from 500 to 200 cm −1 , as in acetylacetonates of Cu 2+ and Ni 2+ where IR bands are reported at 455 and 291 cm −1 , and 438 and 271 cm −1 , respectively [24,25].Being out of the useful range of our instrument, they will not be discussed any further.

Electronic Spectra.
The electronic spectra of the Co and Cu complexes (Figure 3) show in the UV strong bands at 280 nm (Co) and 284 nm (Cu) and shoulders at 345 and 350 nm, respectively.In the visible region there appear a medium intensity broad band with maximum absorption at 510 nm (Co) and 490 nm (Cu) which give rise to the intense dark red color exhibited by the complexes.These bands may be due to the conjugated system mesomeric: O2-C10 = C9-C8 = O3 ↔ O2 = C10-C9 = C8-O3 (p-quinone ↔ oquinone) [9].This band could be assigned to a transition (π → π * ) of the quinone carbonyls [25].
The electronic absorption bands of aromatic rings assigned to π → π * transitions are observed at 214 and 231 nm (benzene ring), 277 nm (quinone ring), and 340 nm (benzene ring) [24].In the electronic spectra of the complexes we observe a sharp and intense band at 238 nm and weak shoulders at 271 and 341 nm that could be attributed to those transitions.

Conclusions
From the above discussion, we can draw the following main conclusions.
(i) We confirm here the chelating versatility of lapacholate ligand toward transition metal ions, through their phenol and ortho and para carbonyl oxygen atoms, by reporting two new isostructural M(Lap) 2 (DMF) 2 (M: Co, Cu) members of an ever growing family of lapacholate-metal complexes.We also demonstrate the ability of DMF molecule (along with other polar solvents like water and ethanol) to complete octahedral binding sites around metal in lapacholate complexes.(ii) We have determined the vibration structure of the new complexes by assigning most of their modes and characterized common features that relate the isostructural pair to each other and to other members of the lapacholate-metal family of complexes.(iii) The dark-red color of the complexes can be traced to a strong and broad electronic absorption band centered at about 510 nm (Co) and 490 nm (Cu) in the UV-visible spectra which can be assigned to pquinone ↔ o-quinone mesomerism in the quinonic ring conjugated system.Listings of fractional coordinates and equivalent isotropic displacement parameters of the non-H atoms (Tables S3a, b), full intramolecular bond distances and angles (Tables S4a,b), anisotropic displacement parameters for the non-H atoms (Tables S5a,b), and hydrogen atoms positions (Tables S6a,b) are provided as Supplementary Material available online at doi:10.1155/2012/973238.

10 Scheme 1 :
Scheme 1: Molecular structure of Lapachol with carbon labeling as in the X-ray study.

Figure 1 :
Figure 1: Drawing of Cu(Lap) 2 (DMF) 2 complex showing the labeling of the non-H atoms and their displacement ellipsoids at the 50% probability level.Cu(II)-ligand bonds are indicated by dark lines.

4. 4 .
Thermogravimetric (TGA) Analysis.As expected, the thermogravimetric data for both isostructural complexes are very similar to each other.The TGA recording for [Co(Lap) 2 (DMF) 2 ] is shown in Figure4.The first step ends at about 250 • C and has a mass loss of 20.8% and corresponds to the elimination of two molecules of DMF (theoretical value: 21.2%).The second and third steps between 275 • C and 450 • C correspond to the oxidation reaction of the lapacholate groups.The total mass loss is 88.6% while the expected value for the formation of the Co 2 O 3 is 87.9%[18].

Table 1 :
Crystal data and structure solution methods and refinement results for M(Lap) 2 (DMF) 2 (M: Co, Cu) complexes.