SYNTHESIS, SPECTRAL CHARACTERIZATION AND ANTIFUNGAL STUDIES ON LANTHANUM (III) AND PRASEODYMIUM (III) COMPLEXES WITH N2O2DIAZADIOXAMACROCYCLES

Priti Tripathi, Akhilesh Kumar Srivastava, Om Prakash Pandey and Soumitra Kumar Sengupta Department of Chemistry, DDU Gorakhpur University, Gorakhpur 273009, India. ...................................................................................................................... Manuscript Info Abstract ......................... ........................................................................ Manuscript History Received: 01 September 2020 Final Accepted: 05 October 2020 Published: November 2020

A novel series of N 2 O 2 diazadioxamacrocyclic complexes of type [Ln(mac)Cl 3 ] has been synthesized via the condensation reactions of a 3-(phenyl/substituted phenyl)-4-amino-5-hydrazino-1,2,4-triazoles with salicylaldehyde and 1,4-dibromobutane in the presence of lanthanum(III) chloride and praseodymium(III) chloride in ethanol. All the newly synthesized compounds were characterized by elemental analysis, electronic absorption, IR, 1 HNMR. The particle size of the complexes have been calculated from XRD spectral using Debye-Scherrer formula and these are found to be in 29-31 nm range. In order to evaluate the biological activity of Schiff bases and to assess the role of Ln(III) and Pr(III) metal on biological activity, the hydrazine triazole Schiff bases and their lanthanide complexes have been studies for in vitro antifungal activity against Fusariumoxysporum, CurvularialunataandColletotrichumfalcatum.
The reactions of a metal ion by a macrocyclic ligands and modification of the resulting complexes controlled to a large extent by a match between the size of a ligand hole and that of the metal ion 4 . There has been considerable activity concerned with the synthesis of cyclic systems, which also contain appended side chains incorporating additional donor functions 5 . Such products have been obtained both from structural modification of selected simple rings as well as via synthetic procedure design to produce the required macrocycle directly from non-cyclic precursors 6 . Many ligands of this category offer the prospect of inducing axial metal-ion coordination even for those cases where the pendant arms incorporate weak donor functions. The use of metals as templates in such reaction has led to the synthesis of metal complexes of macrocyclicligands.Severalmacrocyclic complexes have been synthesized by the template condensationand this provides an opportunity to design and study the model biological systems to understand the chemical changes taking place in such cases [7][8] .
Macrocyclic ligands form stable complexes with lanthanides and actinides. Macrocyclic complexes of lanthanides are currently attracting much attention as pharmaceuticals, in radioimmunotherapy, radio immunography (-Scientigraphy), as contrast-enhancing agents in magnetic resonance imaging, as NMR shift reagents and relaxation 2 agents for proteins and biological cations as fluorescent probes in fluoroimmunoassay. There is an emerging interest in the application of macrocyclic ligands as effective metal ion chelators and in the separation of lanthanides. One of the most tantalizing applications of lanthanide(III) macrocyclic complexes is the efficient catalytic cleavage of RNA. Dinuclearlanthanide(III) complexes are also important as novel tunable photonic devices and potential application in biomedical diagnostics and fluorescent imaging. They are also important in studying the molecular recognition processes which govern the lanthanide(III) cations pairing events. There is no report available on simultaneous study of synthesis, spectral and biological activity of newly synthesized this complexes so far. So that, in the present communication, authors were focused on simultaneous study of synthesis, spectral and biological activity of newly synthesized lanthanum(III) and praseodymium(III) complexes with N 2 O 2 diazadioxamacrocycles

Experimental:
All the solvents and chemicals used were of reagent grade and used without further purification. Lanthanum(III) and praseodymium(III) chloride was procured from Aidrich Chemical Co., England. 3-(phenyl/ substituted phenyl)-4amino-5-hydrazino-1,2,4-triazoles were prepared by a previously reported method 9 . The progress of the reaction, throughout the synthesis, was monitored by TLC. The physical measurements and analytical methods were the same as those described previously. Elemental analyses (C, H and N) were measured with a Perkin-Elmer 1400C analyzer. The lanthanum(III) and praseodymium(III) metal was estimated gravimetrically as oxide form. Infra-red spectra (4000-200cm -1 ) of the ligands and complexes were recorded as KBr pellets on a Nicolet-5700 FTIR spectrophotometer. The room temperature magnetic susceptibilities were measured by Gouy's method using Hg[Co(NCS) 4 ] as calibrant. Electronic spectra of the complexes were recorded on Varian Cary-100 Bio UV-Vis spectrophotometer using DMSO as solvent. Conductance measurements were recorded in DMSO (10 -3 M) using Elico conductivity bridge type CM-82, provided with a dip type conductivity cell fitted with Pt electrodes. The particle size of the complexes has been calculated by analysis of the X-ray diffraction pattern, obtained using an Xray powdered diffractometer (RigakuGeigerflex) with Cu Koe 1( λ = 1.54060 Ả) source.
The empirical formulae, color, percentage yield, elemental analyses values are listed. Synthesis of the macrocyclic complexes are schematically represented in the Table 1(a) and Table 1

(b).
Steps used for fungicidal activityIn vitro antifungal activity: All newly prepared Schiff bases and their complexes were screened for their activity against three fungal organisms Colletrotricumfalcatum,Fusariumoxysporum and Curvularialunataby petridishes method [10]. Fungicidal activity of each compound was evaluated at three different concentrations, i.e., 10, 100 and 1000 ppm. For each compound 1% standard solution was prepared and 1 mL of the solution was diluted with 9 mL of the solvent (DMSO). Petridishes of equal diameter were sterilised at 180 o C. Stock solutions of each compound were prepared for three concentration viz. 10, 100 and 1000 ppm. Solution of 1 mL of each concentration was poured in presterilisedpetridishes and 9 mL of agar medium was added immediately. Each dish was rotated on the table top in order to achieve through mixing of medium with the compound. After this, fungus and bacterial strain was inoculated in the dishes (diameter 5 mm). These set were then inoculated at 30 ±2 o C. The colony diameter of the test organism was measured with mm scale after 6 days. The percentage inhibition of the growth of the test organism was calculated by following formula. % inhibition = 100(Cd-Td)/Cd Where Cd = Colony diameter of control Td = Colony diameter of treated set 3 Each set was kept in triplicate.

Minimum inhibitory concentrations:
The minimum inhibitory concentrations (MICs) in 1000, 100 and 10 ppm were noted. To ensure that solvent had no effect on fungal growth, a control test was performed with test medium supplemented with DMSO at the same dilutions as used in the experiment. Fluconazole was used as a standard drug for antifungal activity.

Results And Discussion:-
A new series of diazadioxamacrocyclic lanthanum(III) and praseodymium(III) complexes have been prepared by the template synthesis of Schiff bases derived from 3-(phenyl/ substituted phenyl)-4-amino-5-hydrazino-1,2,4-triazoles and 1,4-dibromobutane in the presence of lanthanum(III) chloride and praseodymium(III) chloride in 1:1:1 M ratio. All the lanthanum(III) and praseodymium(III) complexes are brown to light yellow to orange colored polycrystalline solids and the elemental analyses data agree well with the proposed mononuclear macrocyclic framework. The complexes are stable in the atmosphere and are soluble in DMF, DMSO, acetone and nitrobenzene. Reaction is shown in Scheme 1.

Magnetic moment and electronic Spectra:
All the complexes in which lanthanum(III) acts as a metal are diamagnetic in nature which is in accord with the 5d 0 4f 0 electronic configuration of lanthanum(III). The praseodymium(III) complexes have magnetic moments lie in the range of 3.50-3.60  B . These values of magnetic moments show little deviation from Van Vleck 11 value and that of hydrated sulphate. This is probably due to very effective shielding of 4f electrons from external forces by the overlaying 5s 2 and 5p 6 shells. The f-f electronic bands of praseodymium(III) complexes are obscured by intense change transfer bands. The complexes show broad bands at ca. 17200-17815, 20800-21200, 21700-22000 cm -1 and at ca. 22400-22600 cm -1 corresponding to the transitions from 3 H 4 → 1 D 2 , 3 P 6 , 3 P 1 and 3 P 2 energy levels, respectively. Nephelauxetic ratio (), covalency parameter () and bonding parameter (b ½ ) were calculated in Table 2, using standard procedures [12][13] and were found to lie in the range 0.9883-0.9986, 0.3814-1.1838 and 0.0264-0.0765, respectively. These values suggest that the complexes are slightly covalent and 4f orbitals are very slightly involved in the bonding.

Infrared spectra:
The infrared spectral bands of the lanthanum(III) and praseodymium(III) macrocyclic complexes are presented in Table 3. The tentative assignments of the data for the compounds were made by comparing the spectra of similar systems 14 reported in the literature. The acyclic ligands and their corresponding lanthanum(III) and praseodymium(III) macrocyclic complexes show band at ca. 3210 assigned to (N-H). The strong characteristic peak for azomethine nitrogen appears in the 1640-1620 cm -1 region which shifts downward (ca. 15-20 cm -1 ) in the complexes indicating 15 a decrease in the bond order of C=N due to the coordination of the azomethinenitrogens to lanthanum(III) and praseodymium(III). This has further been confirmed by the appearance of medium bands at ca. 380-410 cm -1 assignable to (Ln-N).
The infrared spectra of the acyclic ligands show medium bands in the 3380-3410 cm -1 due to phenolic oxygens. This disappears in their corresponding lanthanum(III) and praseodymium(III) complexes indicating the coordination of phenolic oxygen atoms. The (C-O) band of the ligands, which occurs at 1265-1280 cm -1 , shifted to 1278-1295cm -1 in the complexes which further suggests the coordination of the phenolic oxygens with the lanthanide(III). The (Ln-O) band appearsat ca. 500 cm -1 . The two moderately strong bands appearing at ca. 710 and 880 cm -1 can be attributed to (N-N) of the hydrazone residue and in plane deformation of triazole ring, respectively. Bands in the 300-320 cm -1 region are assignable to (Ln-Cl).

H NMR Spectra:
Theproton magnetic resonance spectra of lanthanum(III) complexes in Table 4have   4H) protons adjacent to oxygen.

X-ray diffraction study:
X-ray powder diffraction pattern of one representative complex [La(mac 4 )Cl 3 ] is shown inFigure 1. The structural characterization of the complex was carried out from the analysis of X-ray powder diffraction (XRD) patterns obtained using an X-ray powder diffractometer (Bruker AXS D8 Advance) with CuKα 1 (λ = 1.54056 A o ) source. The peaks in the XRD pattern clearly indicate the formation of nanocrystals. The crystallite sizes have been calculated using Debye-Scherer formula 17 given by, D=0.94 λ / β Cos θ, where D is the crystallite size, λ is the wavelength of X-ray used;  is the full width at half maximum (FWHM) and is the Bragg angle of diffraction. The average crystallite size of the complex was found to be 30.32 nm.
The indexing of the powder patterns for each complex was carried out using the program N-TREOR. The Miller indices (hkl) relate the peak positions or d-spacings to the lattice parameters by an equation specific to the crystal system. The initial unit cell (lattice) parameters were also determined by N-TREOR 18 . These unit cell parameters were refined from the regression analysis and the best crystal system and space group were assigned using CHEKCELL 19 program. It was found that the complex reveals monoclinic crystal system with the most probable space group P2 / c. The lattice parameters and observed & calculated X-ray diffraction data for the complex has been shown in Table 5.    Table 3:-Infrared spectral bands of Schiff bases derived from 4-amino-3-(phenyl / substituted phenyl)-5-hydrazino-1,2,4triazoles and salicylaldehyde with 1,4-dibromobutane and their corresponding macrocyclic complexes of lanthanum(III) and praseodymium(III) complexes.

Complexes / Drugs
10 shows that complexes are 29-31 nm in size. All complexes show slightly higher activity as compared to free ligands to all fungi.