A quantitative analysis of N & O donor chelating ligand complexes

Introduction

The coordination, analytical as well as industrial chemistry are highly important to understand the formation and stability of quinoline and p-toluenesulphonamide with a number of metal complexes have attracted special attention because of their therapeutic properties and to know the exact experimental methods of their investigation have already been discussed 1 . Some of the sulphonamides were used as drugs for diseases like diabetes, dengue, tuberculosis, leprosy, malaria, cancer and convulsion and they were found to active against different types of bacteria. It has been observed recently that some drugs have increased activity when administered as metal complexes more so their metal chelates. Similar indication was found in our previous work. In continuation our previous work and to test the change in antibacterial activity of ligands on chelation, we report here the synthesis of metal chelates viz., 5-iodo-8-hydroxy N(4-methylphenyl)quinolyl-4-sulphonamide and 5iodo-7-chloro-8-hydroxy N(4-methylphenyl) quinolyl-4-sulphonamide with di and tri positive transition metals. Beside their synthesis and characterization of number of mixed chelating complexes of transition metals have been reported in our research lab [2,4] . Some of the research work has predicted that normal geometries of the compounds experience distorted as the 'bite' of the bidentate ligands change.

The solid complexes that separated out were washed with distilled water and dried over P 4 O 10 in vacuum desiccator. Ligands and their complexes were subjected to analysis for C, N, S, Cl, I, whereas metal was estimated gravimetrically in the lab 6 . IR spectra of the ligands and their complexes were recorded in FT/IR-4100 type in KBr / nujol mull phase 4000-200 Cm -1 , ITL Labs Pvt. Ltd. Delhi. Electronic spectra of the complexes were recorded with the help of UV-Beckman Du-2 spectrophotometer. Molar conductance of the complexes in different solvents viz., nitrobenzene, DMF & DMSO in 10 -3 M dilution were observed at 27 o C by Philips conductivity-bridge RP-9500 with a dip type conductivity cell. Magnetic susceptibility measurement were carried out by Gouy balance using HgCo(SCN) 4 as standard. Mass spectra of the ligands and their complexes were recorded at the ToF magnetic sector and Quadruploe-SIMS instrument at New Delhi. The molecular weight determination [7] was carried out by Rast's method using camphor as a solvent. The biological activities were tested against antimicrobial and anti-fungal activities as compared to respective standard drugs using the disc diffusion methods [8] .

Result and Discussion: Ligands and their complexes were subjected to elemental analysis and results are reported in Table-1 the exact melting points could not be determined but were more than 300 0 C, data revealed that the ligands have reacted with metals in 1:3 (M:L n ) ratio where n= 3. On the basis of analysis the general formula of the complexes came out to be ML n . There is a significant difference in the melting point of all complexes formed with ligands, which indicates that the complexes may have been formed. All the complexes were found to be insoluble in common organic solvents but soluble in nitrobenzene, DMF and DMSO. The molecular conductance at 27 0 C indicated the nonelectrolytic nature of the complexes. The low values of molar conductance (~2/20) ohm -1 Cm 2 mol -1 in nitrobenzene, DMF and DMSO medium (Table -1) indicate that the complexes are non-electrolytes. The electronic spectra of all complexes were recorded in solid state. Since the colour of all complexes were different, the spectra of all were found to be almost the same in nature. The Ti +3 complexes shows magnetic moment (1.74-1.78 B.M.) for one unpaired e -1 . The higher values may be due to orbital contribution [9,10] . A single broad band has been observed at range 19221-19225 cms -1 for Ti +3 complexes derived from the transition 2 T 2g → 2 E g for an octahedral geometry [9,10] . These bands are unsymmetrical in shape are indeed made up of two closely shaped bands. The second band appears as a hump and may be due to the presence of John-Teller distortion in the complexes. But regular octahedral stereo chemistry would experience distortion due to the presence of chelating agents that too of a dissimilar nature. Hence, it is concluded that Ti +3 complexes reported in this manuscript are mixed chelating complexes and possessing distorted octahedral geometry. The electronic spectrum of V +3 complexes were recorded which showed band at 15992 -15996 cm -1 with shoulder at 21017-21023 cms -1 . The low energy band has been assigned to 3 T 1g → 3 T 2g whereas the high energy band 3 T 1g → 3 T 1g transition, respectively, characteristics of octahedral geometry [11] . Which is further confirmed by absorption spectrum and magnetic moment values 2.63-2.78 B.M. for V +3 complexes. The spectral result for the six coordinated VL 3 and VLʹ 3 complexes are characteristic of an octahedral geometry around the central V +4 ion of the three expected low energy ligand field bands, two are easily observed in the 12868-13330 and 16945-17854 cms -1 ranges and are assigned as 2 B 2g → 2 A 1g and 2 B 2g → 2 B 1g transitions, respectively. Since, the energy separation between the 2 B 1g and 2 B 2g levels occur at ca. 2000 cm -1 . The frequency of this electronic transition is taken to correspond to 10Dq. The strong high energy band in the 27395-27775 cm -1 range may be assigned to a spin forbidden charge transfer transitions.

The magnetic moment of the examined Cr +3 metal complexes as well as the electronic absorption spectra in DMF (10 -3 cm -1 ) were measured at room temperature. The Cr +3 complexes displayed two absorption band at 15037 and 16529 cm -1 correspond to be the transitions 4 A 2g (F)→ 4 T 2g (F) and 4 A 2g (F)→ 4 T 1g (P), respectively, in an octahedral configuration [12] . The octahedral geometry around the Cr +3 ion was confirmed by the Cr +3 complexes magnetic moment values 3.4-3.5 B.M. The octahedral geometry of Mn +2 complexes were confirmed by the magnetic moment values 5.22-5.61 BM.

One absorption band exhibited in the electronic spectrum of Mn +2 complexes at range17064-17301cm -1 as a result 6 A 1g → 4 T 2g (G) transition in the octahedral geometry [13] .

In the Fe +2 complexes a shoulder band at range 27027-27030 cm -1 in the spectrum is attributed to n→π* transition. The band at range18018-18020 cm -1 with a shoulder around 20202 cm -1 is assigned to T 2g →π* transition which is responsible for intense colour of Fe complexes. Dq value of about 924 cm -1 calculated from the maximum of the major (d→d') band suggested octahedral structure for these complexes [12,13] .

In the Co +2 complexes bands at range 9523-9528 and 20747-20749 cms -1 are assigned to the transitions 4 T 2g (F)→ 4 T 2g (F) and 4 T 1g (F)→ 4 T 1g (P), respectively. The energy of 4 T 1g (F) → 4 A 2g (F) transition has been calculated to be 22886 cm -1 .

The spectrochemical parameters of these complexes, Dq= 838.23 cm -1 , β=0.78, B'=8.73.2-cm -1 and magnetic moment of 3.74-3.98 B.M. confirm their octahedral structure [14,15] . In the Ni +2 complexes the electronic spectral bands at ranges 30310-30312 cm -1 , 17852-17854 cm -1 and 10750-70752 cm - 1 are due to 3 A 2g (F)→ 3 T 1g (P), 3 A 2g (F)→ 3 T 1g (P), 3 A 2g (F)→ 3 T 1g (F) and 3 A 2g (F)→ 3 T 2g (F) transitions. All these transitions are spin allowed transition and are designated as V 3 , V 2 and V 1 , respectively. The ratio of V 2 /V 1 (17850/10750) comes out to be 1.66 which suggested octahedral geometry to these complexes. Values of various ligand field parameters viz., Dq (1075 cm -1 ), B' (1060 cm -1 ) and β (0.98) further substantiate the above conclusion. The magnetic moment of 3.10-3.25 B.M. for both the complexes of nickel also confirm the assigned geometry [15] . The magnetic moment of the Cu +2 complexes at room temperature lie in the range (1.83-1.85 B.M.). These spin allowed transition may be expected in the visible region and the E g and T 2g levels of 2 D free ion will split in to B 1g , A 1g , B 2g and E g levels, respectively. The electronic spectrum of six coordinated copper complexes display band at 13698, 15151, and 23202 cms -1 corresponding to the transitions 2 B 1g → 2 B 2g , 2 B1 g → 2 E g and 2 B 1g → 2 A 1g indicate that the both complexes of copper also confirm the octahedral geometry [15] . The ir spectrum data of the ligands and their complexes were recorded. A broad distinct band at 2960 cm -1 in the spectrum of 5-iodo-8-hydroxy N(4-methylphenyl)quinolyl-4-sulphonamide and another at 3110 cm -1 in 5-iodo-7chloro-8-hydroxyN(4-methylphenyl) quinolyl-4sulphonamide ligands were found [4,13,16] . These values are less than the prescribed limit (3700-3300 cm -1 ) for -OH group. It is due to hydrogen bonding. On the basis of intramolecular hydrogen bonding chelate structure (-O-H…N-) have been proposed for the ligands. A critical examination of the spectra of metal chelates indicate that the bonds at 2960 cm -1 and 3110 cm -1 present in the ligands shift to higher values (3600-3300 cm -1 ) in the chelates. Thus on the metal chelate formation the band between 3600-3300 cm -1 which appears in all chelates are not present in the original ligands. The disappearance of H-bonded -OH in the ligand and its reappearance in the metal chelates are suggestive of O-M-N bond formation, where M is a metal atom. The bands of medium intensity around 1610 cm -1 in the spectra of ligands due to γ(>C=N-) shift to lower values with weak intensity in the spectra of chelates. It is due to M←N bond formation. The bands between 1610-1495 cm -1 are due to 520 cm -1 and 810 cm -1 are due to > CH-I and > CH-Cl, respectively [13,16] .The presence of sulphonamide group has been established by a characteristics band in the vicinity of the region 1375 cm -1 . The mass spectra data of ligands and their metal complexes given in table-2, which exhibit some peaks illustrate the power fragmentation. In most cases instance molecular ion peaks were recorded, which were in good agreement for expected values [17] . The mass spectra of the ligands give some peaks at 425 m/z and 458 m/z, respectively, due to the loss of e [18,19] . All di & tri positive metal complexes (ML 3 , ML' 3 ) reveal antimicrobial activity and they were found to be active inhibitors against bacteria-fungi strains (table-3).

Responsiveness of both the testing coordinated complexes ML 3 & ML 3 ′ (M=Ti +3 , V +3 , VO +2 , Cr +3 , Mn +2 , Fe +2 , Co +2 , Ni +2 , Cu +2 , L= 5-iodo-8-hydroxyN(4methylphenyl)quinolyl-4 --sulphonamide, L ′ = 5-iodo-7chloro-8-hydroxy(4-methylphenyl)quinolyl-4sulphonamide) was evaluated based on the diameter of the inhibition zone against gram+ve (S. aureus, B. subtilis) and gram -ve (E. coli, P. aeruginosa) bacteria and two fungal (C. albicans, A. niger) strains. The analysis of results presented in table-3 shows the antibacterial activities of nine different metal-ligand complexes against gram+ve bacterial strain. Using this data an attempt has been made to explain the comparative studies through Fig. a,b,c,d,e. In vitro screening for all coordinated complex was performed at different concentration mentioned above and the result were compared with chloramphenicol antibiotic. The values of the diameter of inhibition zone of CuL 3 & CuL 3 ′ complexes show that these antimicrobial agent are effective in controlling the growth of all the bacteria strains studied when compared with the positive (chloramphenicol) and Cu complexes were also effective against S. aureus, E. coli and P. aeruginosa, respectively. The result also point out that the TiL 3 & TiL 3 ′ complexes are less active than other complexes but like other metal chelates these chelates also showing significant inhibition activity against fungi C. albicans & A. niger [20] . In comparison of the standard drugs fluconazole all metal chelates exhibited anti-fungal activity. Among all testing complexes CuL 3 & CuL 3 ′ complexes were most active against all fungal strains. DMSO (-ve control) has shown negligible activity as compared to these complexes. The metal complexes exhibited different levels of activities against various strains because of variation in cells wall permeability. Inhibition depends on metal complex concentration, culture medium and incubation conditions [20,21] . The antimicrobial activity of the synthesized compounds might be explained on the basis of the overtone concept and chelation theory. Accordingly, polarity of metal-atom gets reduced due to sharing of the partial (+) charge of metal ion to the different donor atoms of the compounds and some pelectrons delocalization inside the entire chelates. Some metal complexes do not show good activity because of their limited lipid solubility, therefore, metal ions present on center may not be able to attack the required site of cell wall to interfere with the normal cell activity. Although chelation enhances the biological activity of the complexes along with other factors like dipole moment, geometry of the complexes, concentration, size of the molecules, bond length, coordination site and hydrophobicity effect activity. Hence it may be concluded that not only chelation but may other contributions also enhance the antimicrobial activity [22] .

Conclusion

Di & tri valent transition metal complexes with biologically active mixed ligands were synthesized in stoichiometric ratio, the ligands function as anionic chelating ligands through deprotonated N, O atoms. The ligand field parameters of the synthesized complexes have been evaluated which suggested to be distorted octahedral geometry. Antimicrobial activities of free ligands and their metal complexes were measured, data prove that the complexes CuL 3 & CuL 3 ′ were found most active complexes followed by cobalt & vanadium, whereas TiL 3 & TiL 3 ′ complexes were found less active as compared to standard drugs fluconazole, all metal chelates exhibited significant anti-fungal activity. The significance of this investigation is to uncover shielding and constructive therapeutic agents that wield against bacterial and fungal infection, all chelates exhibited anti-fungal activity. The molecular docking of the both ligands and its complex with enzyme sterol 1, 4-𝛼 Demethylase suggested the hydrophobic binding. Furthermore, in the silico stressed that the compounds may be used as orally active drugs.

Acknowledgement

AcknowledgementThe authors are thankful to Principal, Hindu College, Moradabad for providing necessary facilities and financial assistance. My heartfelt gratitude to Professor Rakesh Kumar, Department of Mathematics, Hindu College, Moradabad, contributed whole heartedly to make this manuscript excellent. Special thanks to staff department of Chemistry, Bareilly College, Bareilly who helped in the sample analysis.

References

1. Labuda J, Skatulokora M, Nemeth M, Gergely S. Formation and stability of diethyldithiocarbamate complexes. Chem Zvesti. 1984;38:597-605.
2. Baboo M. Synthesis and characterization of mixed bidentate ligands. Quart J Manag Dev. 2010;41(3):8083.
3. Dayaveer, Baboo M. Synthesis and spectral studies of some transition metal complexes. Orient J Chem. 2012;28(4):1797-1802.
4. Baboo M. Synthesis and spectral studies on transition metal(II) complexes of polydentate Schiff base. Int Res J Com Art Sci. 2014;5(6):363-385.
5. Kepert DL. Spectral studies of bidentate ligands with transition metal(II and III) complexes. Inorg Chem. 1972;11:1561-1565.
6. Vogel AI. Textbook of Quantitative Inorganic Analysis. London: Longman; 1961.
7. Simpson W. Determination of molecular weight by cryoscopy method. Nature. 1944;154:705-706.
8. Zaidan MRS, Noor Rain A, Badrul AR, Adlin A, Norazah A, Zakiah I. In vitro screening of five local medicinal plants for antimicrobial activity using disc diffusion method. Trop Biomed. 2006;22(2):165-170.
9. Lever ABP. Inorganic Electronic Spectroscopy. 2nd ed. New York: Elsevier; 1986.
10. Siig OS, Kepp KP. Iron(II) and iron(III) spin crossover: Towards an optimal density functional. J Phys Chem A. 2018;122:4208-4217.
11. Jasinska A, et al. Vanadium(III) and vanadium(IV) Schiff base complexes as potential insulin-mimetic compounds: Comparison, characterization and biological activity. Polyhedron. 2022;215:115682.
12. Ben Amer YO, et al. Synthesis and characterization of Cr(III) and Fe(II) bis(2-methoxybenzylidene)biphenyl4,4′-diamine complexes. Open J Inorg Chem. 2020;10:6-14.
13. Mir MA, Hasnain SM. Mixed Schiff base and 8hydroxyquinoline complexes with Mn, Fe and Zn: Synthesis, characterization and properties. In: Trends in Environmental Sustainability and Green Energy. Conference Proceedings; 2024 Jan 21. p. 151-161.
14. Elmagbari FM, et al. Synthesis and characterization of Cr(III) and Co(II) Schiff base complexes. Mater Sci Appl. 2023;14(2):53-62.
15. Abdulkarem AA. Synthesis and antimicrobial studies of Cu(II), Ni(II) and Co(II) metal complexes with a tridentate ligand. Biophys Chem. 2017;8:13-21.
16. Dyre JR. Applications of Absorption Spectroscopy of Organic Compounds. 2nd ed. New Delhi: Prentice Hall India Learning Pvt Ltd; 1978.
17. Gross JH. Mass Spectrometry: A Textbook. 3rd ed. Berlin: Springer; 2017. p. 55-150, 327-437.
18. Gotz A, Heumann KG. Iron isotope ratio measurement with the thermal ionization technique using a compact quadrupole mass spectrometer. Int J Mass Spectrom Ion Process. 1988;83(3):319-330.
19. Pali SP, et al. Mass spectrometry of coordination of transition metals with tetradentate ligands: Isomeric Ni(II) complexes based on substituted isothiocarbohydrazides and the structure of small ions derived from them. Int J Mass Spectrom. 1999;193(23):131-141.
20. Wadher BJ, Bhoosreddy GL. Manual of Diagnostic Microbiology. 1st ed. Mumbai: Himalaya Publishing House; 1995.
21. Malik MA, et al. Heterocyclic Schiff base transition metal complexes in antimicrobial and anticancer chemotherapy. Med Chem Commun. 2018;9(3):409436.
22. Spectroscopic, thermal, anticancer and antibacterial activity studies. Spectrochim Acta A Mol Biomol Spectrosc. 2015;148:76-89.