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Boletín de la Sociedad Chilena de Química

Print version ISSN 0366-1644

Bol. Soc. Chil. Quím. vol.45 n.3 Concepción Sept. 2000 



Department of Chemistry, University of Rajasthan, Jaipur-302004, India
(Received: Frebuary 23, 2000 - Accepted: June 28, 2000)

In memorian of Dr. Guido S. Canessa C.


This paper decribes the synthesis and characterization of several new tetraazamacrocyclic complexes of Pb(II). The template condensation of adipic acid with primary diamines, i.e., ethylenediamine and propylenediamine in the presence of lead salts resulted in the formation of macrocyclic complexes. The geometry and the mode of bonding of the resulting complexes have been inferred from chemical analysis, IR and 1HNMR spectral studies, molecular weight determinations and conductivity measurements. An octahedral geometry around the lead ion is suggested for the [(PbMacn)X2] (X = Cl, NO3 or CH3COO) complex. Based on molecular weight determinations and conductivity measurements, their monomeric and non-electrolytic nature has been confirmed. The biological activities of all the lead salts and their metal complexes have been studied by screening the compounds against organisms such as, E. coli, S. aureus, F. oxysporum and A. alternata and the results have been compared.

KEYWORS: Adipic acid, primary diamines, metal complexes, antibacterial activity , antifungal activity.


Este paper describe la síntesis y caracterización de nuevos complejos tetraazamacrociclos de Pb(II). La condensación en el templado de ácido adípico con aminas primarias p. ej. etilendiamina y propilendiamina en presencia de sales de plomo dieron origen a la formación de complejos macrociclos. La geometría y el modo de unión de los complejos resultantes se han determinado por análisis químico, estudio espectroscópico de IR y 1H RMN, determinaciones de pesos moleculares y medidas de conductividad. Se sugiere una geometría octahédrica para los complejos de plomo [(PbMac)nX2] (x=Cl, NO3 o CH3COO). Basado en las determinaciones de pesos moleculares y medidas de conductividad se ha confirmado su naturaleza monomérica y no-electrolítica. Las actividades biólogicas de todas las sales de plomo y sus complejos metálicos se han estudiando ensayando los compuestos con otros organismos como E. Coli, S. Aureus, F.Oxysporum y A. Altervate, cuyos resultados se han comparado.

PALABRAS CLAVES: Acido adípico, diaminas primarias, complejos metálicos, actividad antibacteriana, actividad fungicida.


The macrocyclic complexes have attracted both inorganic and bioinorganic chemists in recent years1). Naturally occuring macrocycles were shown to be capable of activity transporting metal ion across membranes, beginning with valiomycin2). Synthetic macrocyclic ligands have been shown to form very stable complexes with alkali and alkaline earth metal cations. These complexes can be used as models for investigation of ion transport throughout membrane in biological systems3). The potentialities of tetraaza synthetic macrocyclic complexes as models for more complex natural system is now well recognised4). In these macrocyclic complexes, both the metal ion and the size of the ring play an important role. The saturated macrocycles with various numbers of their ring membered have been synthesized consistently. These compounds have produced interesting informations concerning both the stabilities and structure of their metal complexes5). Organolead compounds possess fungicidal as well as bactericidal activities6,7). It has also been suggested that these are suitable for the treatment of various allergies, asthma and influenza8). Several organolead compounds find uses as good algicides, herbicides and also as anticancerous agents9-11). The applications12-14) of macrocyclic compounds in bioinorganic chemistry, catalysis, extraction of metal ions from solution and the activation of small molecules gave impetus to this endeavour.

The synthesis of some new lead(II) complexes of twenty and twenty two membered tetraazamacrocyles from reaction of primary diamines with dicarboxylic acids, their structural elucidation and biological screening are reported in the present paper.


All the chemicals used during these investigations including ethylenediamine, propylenediamine (E. Merck) and adipic acid (Fluka) were used without further purification. The metal salts PbCl2, Pb(NO3)2 and Pb(CH3COO)2 used were of B.D.H. quality. All of the solvents were dried before use. Moisture was excluded from the glass apparatus using CaCl2 guard tubes.

Synthesis of complexes

Synthesis of (2,7,12,17-tetraoxo-1,8,11,18-tetraazacyclododecane)lead(II) chloride, nitrate and acetate, [(PbMac1)X2]

The reaction is carried out in 1:2:2 molar ratio. An ice cold solution of metal salts [PbCl2, Pb(NO3)2 and Pb(CH3COO)2 (0.005 mol)] in methanol (25 ml.) was reacted with ethylenediamine (0.01 mol) dissolved in methanol (25 ml.). This is followed by the addition of a methanolic solution (25 ml.) of adipic acid (0.01 mol) and put in a magnetically stirred 100ml. round-bottom flask. The resulting mixture after stirring for 12h, was then kept for 8h at room temperature which resulted in the formation of fine, colourless compounds. These were washed with methanol and dried. These compounds were recrystallized in benzene and dried again in vacuo.

Synthesis of (2,7,13,18-tetraoxo-1,8,12,19-tetrazacyclodidodecane)lead(II) chloride, nitrate and acetate, [(PbMac2)X2]

The method is same as described above. The reagents used were metal salts [PbCl2, Pb(NO3)2 and Pb(CH3COO)2 (0.005 mol), propylene diamine (0.01 mol) and adipic acid (0.01 mol).

The resulting products were washed with MeOH in which all of the starting materials are soluble but the complexes are insoluble. Therefore, any unreacted material was washed out and the compound so obtained were completely pure. Their purity was further checked by T.L.C. using silica gel-G.

Analytical Methods and Physical Measurements

The IR spectra (4000-200 cm-1) were recorded on a model Nicolet Megna FTIR-550 spectrophotometer in the form of KBr pellets. The electrical conductivities of 10-3M solutions in dry DMF were obtained on a Systronics type 305 conductivity bridge. Melting points were determined in capillary tubes and were uncorrected. Molecular weights were determined by the Rast Camphor Method. The 1HNMR spectra were obtained in DMSO-d6 using Jeol FX 90 Q spectrometer with Me4Si as an internal

standard. Chemical shifts were reported in ppm units. Lead was estimated as lead sulphate gravimetrically. Nitrogen and chlorine were determined by Kjeldahl’s and Volhard’s methods, respectively15). Carbon and hydrogen analyses were performed at central Drug Research Institute, Lucknow, India.

The biological activity of metal salts and metal complexes were studied by screening the isolated complexes against E. coli and S. aureus for antibacterial and against F. oxysporum and A. alternata for antifungal activity. The microbial screening for antibacterial and antifungal activities were done by paper dise plate method16) and agar plate technique17).


The reactions of lead salts with primary diamines and dicarboxylic acids in 1:2:2 molar ratio in dry methanol can be represented by the following Fig.1.

Conductance values (12-18 ohm-1 cm2 mol-1) in anhydrous DMF at 10-3M concentration show them to be non-electrolytes. These complexes are soluble in DMF and DMSO but insoluble in common organic solvents. Their physical properties and analytical data are given in Table-I.

Table I. Analysis and physical characteristcs of the lead (II) complexes.

Spectral Studies

IR Spectra

The preliminary identification of the ligand precursors (primary diamines and dicarboxylic acids) and complexes have been obtained from IR spectra which show that the bands due to hydroxyl and primary amine groups are absent in the corresponding metal complexes, indicating the condensation of the primary diamines with the dicarboxylic acids and formation of the proposed macrocyclic frame-work. This information together with the appearance of new bands in the 1654-1697, 1504-1526, 1246-1282 and 641-664 cm-1 regions assignable to amide I, amide II, amide III and amide IV in plane deformation vibrations respectively18), further suggest the formation of macrocyclic complexes. In the spectra of all the complexes a single peak is observed in the region 3195-3234 cm-1 which may be assigned to n(NH) of amide group. The position of this peak is found to be lowered by ca 40 cm-1 compared to the analogous metal free tetraaza ligands19). The negative shift in nNH mode along with the appearance of a new medium intensity band in the region 415-445 cm-1 assignable to n(Pb-N) vibrations suggested that the amide nitrogen is coordinating to the metal ion. The absence of a band attributable to nPb-O vibration indicated that the amide oxygen is not coordinating (Table II).

Table II. IR Spectral data of the lead (II) complexes.

1HNMR Spectra

The bonding pattern in the resulting macrocyclic complexes has been further confirmed by the proton magnetic resonance spectra of the ligands and their respective metal derivatives. In the spectra of free diamines and dicarboxylic acids, proton resonance signals due to -NH2 and -OH groups were observed, which disappear completely in the spectra of lead complexes indicating condensation and formation of macrocyclic complexes (Table III).

Table III. 1HNMR (d, ppm) Spectral data of the lead (II9 complexes.

In the spectra of the complexes a multiplet arising due to the methylene protons (CO-N-CH2) appears in the region d3.22-3.41 ppm. The complexes of the type [PbMacn)X2] exhibit a broad signal in the region d7.98-8.19 ppm due to amide (CO-NH) protons. Similar data have been reported by several authors20,21) showing the presence of NH group in the macrocyclic ring. However, a multiplet in the region, d1.91-2.03 ppm may be ascribed to the middle methylene protons of the 1,3-diaminopropane moiety. A singlet observed at d3.16-3.27 ppm in the 1HNMR spectra of the lead (II) complexes may be assigned to methylene protons of dicarboxylic acid moiety (CO-(CH2)4-CO) which are adjacent to nitrogen atom. According to the above interpretation we can say that the ligands act as tetradentate chelating agents having four coordination sites. Secondly, since the anions Cl-, NO3- and CH3COO- remained bonded with the metal atom, a hexacoordinated environment around the lead metal atom seems to be reasonable (Fig.1).

Biological Screening

Antifungal Activity

The antifungal activity of lead (II) compounds have been evaluated against Fusarium oxysporum and Alternaria alternata by the agar plate technique17) using czapek’s agar medium (sucrose, agar-agar, KCl, KH2PO4, NaNO3, FeSO4 and MgSO4). The compounds were dissolved in 125, 200 and 250 ppm concentrations in DMSO and diluted with distilled water and then mixed with medium. Controls were also run and three replicates were used in each case. The linear growth of the fungus was obtained by measuring the diameter of the fungal colony after 96h (Table IV).

Table IV. Antifungal screening data for the Pb (II) macrocyclic complexes.

The percentage inhibition in all of the replicates was calculated by the equation.

Percentage inhibition =

where C and T are the diameters of the fungus colony in the control and test plates, respectively.

Antibacterial Activity

Bactericidal activity of lead (II) compounds were evaluated against Escherichia coli(-) and Staphylococcus aureus(+) by the paper disc plate method16). The nutrient agar medium (peptone, beef extract, NaCl and agar-agar) and 5mm diameter paper disc (Whatman No.1) were used. The compounds were dissolved in DMSO and diluted with distil water in 500 and 1000 ppm concentration. The filter paper discs were soaked in different solutions of the compounds, dried and then placed in the petriplates previously seeded with the test organism. The plates were incubated for 24-30h at 28+2ºC and the inhibition zone, thus formed around each disc containing the test compound was measured (in mm). The results of these studies are shown in Table V.

Table V. Antibacterial screening data for the Pb(II) macrocyclic complexes

The results given in Tables IV and V reveal that all the compounds are active against these organisms, even at low concentrations and the inhibition of the growth of micro-organism was found to be dependent on the concentration of the compounds. The results of the antifungal activity indicated that the metal chelates are more active than their parent diamines and dicarboxylic acids but less reactive than their respective metal salts. In the case of antibacterial activity the metal chelates, diamines, dicarboxylic acids and respective metal salts showed similar type of behaviour as indicated in case of antifungal activity except that in the case of lead acetate, lead chelate is having more activity than lead acetate. Chelation reduces the polarity of the metal ion mainly because of partial sharing of its positive charge with the donor groups and possible p-electron delocalization over the whole chelate ring. This increase the lipophillic character of metal complexes, which subsequently favour its permeation through the semipermeable cell membrane of micro-organism and thereby impairing normal cell process22).


The authors are thankful to the Government of India, Ministry of Science and Technology, New Delhi, India, for financial assistance through grant No.SP/S1/F06/96.


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