Reactions of MoCl5 and MoO2Cl2 with Succinimide, 1, 4-Diaminobutane, 3-Methylpyridine, 1, 3-Diaminopropane, Pyrazole and 1- Methylpyrrolidine in Tetrahydrofuran

Introduction

Succinimide

Succinimides¹ are involved in various biological applications. Succinimide is a constituent of various biologically active compounds having significance as: CNS depressant², hypotensive³, antitumour⁴, cytostatic⁵, bacteriostatic⁶, nerve conduction blocking⁷, muscle relaxant⁸, anorectic⁹, antibacterial¹⁰, analgesic¹¹, anti-convulsant¹², anti-tubercular¹³, antispasmodic¹⁴ and antifungal¹⁵.

Succinimide can form complex through oxygen atom. Deprotonated succinimide (on removal of hydrogen from nitrogen)can form complex through the nitrogen atom. In deprotonated succinimide, the CN bond length lies between single and double bond, because the new free electron pair of nitrogen gets delocalized and is spread on both CN bonds due to conjugation between lone pair of nitrogen and π-electrons of C=O bonds¹⁶. This conjugation reduces chances of availability of this lone pair for coordination. So coordination in succinimide through oxygen is more likely.

1, 4-Diaminobutane

1, 4-Diaminobutane^17-19 has a variety of applications in agrochemicals, paint additives, pharmaceuticals, surfactants and micronutrients. It is used as starting material in some biological systems and amido-ureas. It is used in the preparation of nylon 46. It acts as corrosion inhibitor of mild steel in 1N H₂SO₄.

3-Methylpyridine

3-Methylpyridine²⁰ has application in agrochemical industry as chlorpyrifos²¹. 3-Methylpyridine degrades/evaporates slowly from water samples as compared to 2-methylpyridine/4-methylpyridine^{22, 23}. 3-Methylpyridine is precursor to prepare antidote for organophosphate poisoning²⁴. It is used as waterproofing agent²⁵ in textile industry.

1, 3-Diaminopropane

1, 3-Diaminopropane²⁶ has a variety of industrial applications, such as, in epoxy resin and cross-linking agents. It is used as precursor for preparation of pharmaceuticals, organic chemicals and agrochemicals.  It is used²⁷ in the synthesis of heterocycles used in coordination complexes and textile finishing. It is a potential inhibitor^{28, 29} against neoplasia and ornithine decarboxylase enzyme protein on rat urinary bladder carcinogenesis.

Pyrazole

Pyrazoles as well as their derivatives have a lot of biological properties, like antipshycotic^30-32,antimicrobial³³, anticonvulsant³⁴, antitumor³⁵, anti-cyclooxygenase³⁶, analgesic³⁷, antitubercular³⁸, antidiabetic³⁹, antiinflammatory⁴⁰, etc.

1-Methylpyrrolidine

1-Methylpyrrolidine⁴¹ has numerous applications in agrochemicals, pharmaceuticals, colourants, organic synthesis, photographic chemicals, plasticizers, emulsifiers, rubber chemicals, curing agent for epoxy resins, corrosion inhibitors, etc. It is used in PU manufacture as a catalyst. In cosmetics,it acts as a powerful surfactant.It is present in cigarette smoke. It is part of cefepime⁴²: broad-spectrum cephalosporin antibiotic capable to treat bacteria causing pneumonia, infections of the skin and urinary tract.

Transition metals complexes on coordination withligandsundergo deep change in physiological properties of the metals and ligands. Desired properties^{27, 43} on transition metals for particular applications can be incorporated by coordination of metals with certain ligands. It involves modification of properties, like stability of oxidation states, electrophilic/nucleophilic properties and solvophilicity of the metal ions. We have to choose a suitable metal and the ligand after various trials. On coordination, metal and ligand properties undergo a desired change. Many drugs containing metal chelates have higher biological activity than the uncoordinated ligands themselves^44-49. 

Aim of Investigation

MoCl₅ reacts with a variety of bases. The author has investigated^50-55 the reactions of MoCl₅ with 4-phenylimidazole-2-thiol, aromatic azoles, imides, diaminoalkanes, alkylpyridines, 2-thiazoline-2-thiol, thiols and mercaptopyridine-N-oxide sodium.

MoO₂Cl₂ reacts with various bases. The author has investigated^50-58 the reactions of MoO₂Cl₂ with aromatic azoles, alkanediols, diaminoalkanes, imides, amides, thioamides, purine and thiols.

It has been reported that molybdenum may extract^{59, 60} oxygen from oxygen containing ligands. Oxo complexes of above bases with transition metals show numerous applications and are biologically active. So to study the biological activity of molybdenum complexes and to study oxo abstraction reactions by molybdenum, reactions of succinimide/1, 4-diaminobutane/3-methylpyridine/1, 3-diaminopropane/pyrazole/1-methylpyrrolidine with MoCl₅/MoO₂Cl₂ have been carried out. Formulations of these compounds were made and their properties were studied with FTIR, ¹H NMR/¹³C NMR, microbiological studies, elemental analysis and LC-MS.

Materials and Methods

Succinimide, 1, 4-diaminobutane, 3-methylpyridine, 1, 3-diaminopropane, pyrazole, 1-methylpyrrolidine, MoCl₅ and MoO₂Cl₂were procured from Sigma-Aldrich.

The reactants and products are sensitive to air/moisture, so all preparations, separations and isolations were executed in vacuum line and dry atmosphere (dry nitrogen) to eliminate any oxidation/hydrolysis of reactants/products by air/moisture.

Ligand solution in dry THF was dropped from dropping funnel with continuous agitation to MoCl₅/MoO₂Cl₂ solution in THF taken in 100 ml round bottom flask. The reaction was carried out for about 7 h. The products were isolated after filtration through filtration unit fitted with G-4 sintered glass crucible.

Oxinate gravimetric method ⁶¹ was used formolybdenum estimation. Mixture of sodium carbonate and sodium peroxide was fused with a known weight of the sample by using nickel crucible. Contents were fused in muffle furnace for 1 hr. at 400º C. Fused mixture was extracted with distilled water and content was filtered through fine filter paper. Discarded the residue and only filtrate was retained. Added methyl red indicator to the filtrate. 2 N sulphuric acid was added to it dropwise to make it acidic. Added 2N ammonium acetate solution dropwise until colour of solution became faint. Solution was heated to boiling. Added 3% oxine solution (in glacial acetic acid) dropwise until yellow precipitates obtained. Boiled gently with stirring until the precipitation was complete. Filtered the yellow precipitate with G-4 sintered glass crucible Precipitate were washed with hot water, dried at 130-140° C and weighed as MoO₂(C₉H₆NO)₂.

Estimation of chlorine was carried out gravimetrically as silver chloride⁶¹. A known weight of the sample was taken in distilled water. Added 10-12 pallets of sodium hydroxide in it. Content was boiled, cooled and filtered through a fine filter paper. Acidified the solution with dilute nitric acid. Added excess of N/10 aqueous solution of AgNO₃ until white precipitate of AgCl were obtained. Boiled the solution until precipitation and coagulation were complete. Filtered the precipitate through G-4 sintered glass crucible, washed with acetone, dried at 130-140° C and weighed as AgCl.

Carbon, hydrogen and nitrogen were estimated by Thermo Finnigan Elemental Analyser. Perkin-Elmer 400 FTIR Spectrometer was used for obtaining infrared spectra (transmission mode). Multinuclear Brucker Avance-II 400 NMR spectrometer was used for recording¹H/¹³C NMR in DMSO-d₆ solvent.LC-MS spectra in the range 0-1100 m/z have been attained. These studies were executed in SAIF at P. U. Chandigarh.

Molybdenum compounds prepared were tested using agar well diffusion assay methodfor their antibacterial and antifungal potential on the strains: Staphylococcus aureus (gram positive bacteria) (MTCC-737), E. coli (gram negative bacteria) (MTCC-1687), Candida albicans (fungus) (MTCC-227) and Aspergillus niger (fungus) (MTCC-282).Standard drugs amoxicillin and ketoconazole were used for bacteria and virus, respectively as reference. Cultures of MTCC (The Microbial Type Culture Collection and Gene Bank, Chandigarh, India) were used. Drug testing at ISF Analytical Laboratory (ISF College of Pharmacy), Ferozepur Road, Moga, Punjab (India) was carried out.R (Residue)/ F (Filtrate) refer to product source.

Results and Discussions

Elemental Estimation

Percentage of the observed (theoretical) values of the elements has been depicted in Table-1.

Table 1: Elemental Estimation

Compounds	Cl	Mo	H	C	N
Mo2O3Cl5(C4H5NO2)2(C4H8O)2, [1] (Black/759.5)	22.87 (23.37)	24.73 (25.27)	03.23 (03.42)	24.67 (25.27)	04.13 (03.68)
Mo2O2Cl2(C4H5NO2)2(C4H8O)2,[2] (Dark black/637.0)	11.55 (11.14)	29.42 (30.14)	03.68 (04.08)	29.87 (30.14)	04.74 (04.39)
Mo2O2Cl2(H2NCH2CH2CH2CH2NH2)2, [3] (Coffee brown/375.0)	18.23 (18.93)	24.73 (25.60)	06.48 (06.40)	24.79 (25.60)	14.27 (14.93)
Mo3Cl8(C6H7N)4(C4H8O)2, [4] (Coffee red/1088.0)	25.33 (26.10)	25.69 (26.47)	03.39 (04.04)	34.67 (35.29)	04.64 (05.14)
Mo3O6Cl6(C6H7N)6, [5] (Light brown/1055.0)	17.73 (18.44)	24.69 (24.93)	03.93 (03.63)	36.78 (37.40)	06.98 (07.27)
MoO2Cl3(HNCH2CH2CH2NH2)2, [6] (Black/380.5)	27.02 (27.98)	24.67 (25.22)	05.13 (04.73)	17.98 (18.92)	14.13 (14.71)
Mo2O4Cl4(C3H4N2)4, [7] (Black/670.0)	20.68 (21.19)	27.93 (28.65)	02.71 (02.38)	20.98 (21.49)	16.04(16.71)
Mo2O6Cl8(C5H11N)4, [8] (Brick red/912.0)	30.47 (31.14)	20.28 (21.05)	05.36 (04.82)	27.11 (26.31)	05.84 (06.14)

FTIR Spectra

N-H stretching of succinimide^{62, 63}havebeen notedat 3409 cm^-1 & 3221 cm^-1. Strong absorption at 3294 cm^-1 indicates that [1] contains N-H group. Bands at 980 cm^-1 and 919 cm^-1 support the availability of cis-MoO₂²⁺ core^{64, 65}in [1]. Occurrence of cis-MoO₂²⁺ core is due to oxo abstraction^{59, 60} by molybdenum from THF. There is some decrease in C=O sym and asym absorptions. There is decrease in C=O bond order, referring to the presence of O→Mo coordination¹⁶ in [1] (Table-2).

Strong absorption at 3433 cm^-1 indicates that [2] contains N-H group. Bands at 984 cm^-1 and 923 cm^-1 support the availability of cis-MoO₂²⁺ core^{64, 65}in [2]. Occurrence of cis-MoO₂²⁺ core is due to oxo abstraction^{59, 60} by molybdenum from THF. There is some decrease in C = O sym and asym absorptions. There is decrease in C = O bond order, referring to the presence of O → Mo coordination¹⁶ in [2] (Table-2).

Table 2: FTIR absorptions in cm⁻¹

Assignments	Succinimide62, 63	[1]	[2]
N-H str.	3409 s b, 3221 s b	3509.6 sh, 3381.5 sh, 3294.4 s, 3152.4 s, b	3433.5 s b
CH2 sym. str.	2960, 2947 w	2983.7 sh
C = O sym., H – N – C in plane bending	1774 m	1776.9 m, 1756.0 m	1772.8 w
C = O asym., H – N – C in plane bending	1710 vs, b	1686.0 s	1705.2 s, 1637.2 m
CH2 sym. scissoring	1430 m	1415.1 sh
CH2 asym. scissoring	1401 m	1399.1 sh	1399.8 sh
C – N – C asym. str., H – N – C in plane bending	1347 s, 1337	1373.7 m, 1358.9 sh	1373.3 w
CH2 bending, ring in plane bending	1298 s	1297.9 s	1298.1 w
CH2 bending	1240	1248.1 m	1247.1 sh
C – N – C asym. str., H – N – C in plane bending	1189 s,	1183.2 s	1189.9 m
C – C str., CNC sym. str.	849	857.2 w
CH2 bending, ring out of plane bending	820 s	817.1 s
		722.9 s	725.1 m b
OCN asym. out of plane bending	632 m	645.9 s	642.4 m
OCN sym. out of plane bending, CH2 bending	539 w	552.2 w	563.2 m
Mo-N str.			418.0 sh
Mo=O str. of cis-MoO22+ core64, 65		980.6 s, 919.1 w	984.7 w, 923.5 sh

 

N-H stretching of 1, 4-diaminobutane⁶⁶ hasbeendetectedat 3345 cm^-1 & 3278 cm^-1. Strong N-H absorptions have been recorded at 3391 cm^-1, 3077 cm^-1 and 3010 cm^-1 in [3] (Table-3). Terminal Mo=O stretching occurs⁶⁷ at 990 cm^-1 -1010 cm^-1 in various inert solvents. A medium Mo=O stretching^{64, 67, 68} at 921 cm^-1 conforms to the presence of terminal Mo=O group. There is a decline in Mo=O stretching to 921 cm^-1 showing Mo coordination⁶⁹ to 1, 4-diaminobutane through N atom, in a direction trans to Mo=O bond. Bending mode due to NH₂ observed in 1, 4-diaminobutane⁶⁶ at 1146 cm⁻¹ is declined to 1116 cm⁻¹, because of N→Mo coordination.

Table 3: FTIR absorptions in cm⁻¹

Assignments	1, 4-Diaminobutane66	[3]
N-H str.	3345, 3278	3391.2 s, 3077.1 s, 3010.1 s
CH2 str.	2961-2874	2881.1 sh
NH2 bending	1608	1614.2 s
CH2  deformation (strong)	1498, 1391, 1355, 1310	1519.3 m, 1470.7 m, 1448.1 s, 1403.3 w, 1344.4 w
NH2 bending	1146	1184.4 w, 1116.2 s
C-N sym str. (weak)	1071	1025.3 m
CH2 deformation (medium)	862, 736	817.1 s
Mo-N (strong)		498.3 m
Terminal Mo=O64, 67, 68str.		921.2 m

3-methylpyridine^70-73showsring C-H absorptions at 3060 cm^-1 and 3032 cm^-1. Strong bands at 3119 cm^-1 and 3054 cm^-1 have been noticed in [4]. Ring C=N stretching & ring C=N torsion wave numbers have increased and ring C-H bending mode wave numbers have declined due to Mo(dπ)→N(pπ) back bonding. A strong band at 989 cm^-1 revealsthe presence of terminal Mo=O^{64, 67, 68}group in [4] (Table-4).

Strong band at 3391 cm^-1 has been noticed in [5]. Ring C=N stretching & ring C=N torsion wave numbers have increased and ring C-H bending mode wave numbers have declined due to Mo(dπ)→N(pπ) back bonding. A medium band at 989 cm^-1 revealsthe presence of terminal Mo=O^{64, 67, 68}group in [5] (Table-4). Occurrence of terminal Mo=O is due to oxo abstraction^{59, 60} by molybdenum from THF.

Table 4: FTIR absorptions in cm⁻¹

Assignments	3-Methylpyridine70-73	[4]	[5]
C-H ringstr.	3060, 3032	3168.9 s, 3119.9 s, 3054.8 s	3391.0 s b
C-H methylstr.	3002, 2958, 2928	2937.5 sh, 2866.8 sh
ringstr.	1600, 1578	1629.1 m, 1607.1 m, 1543.1 s	1630.7 s, 1554.6 s
Ring C-H bending	1478
C-H methyl assym bending	1458, 1452	1469.1 m	1474.2 m
Ring C-H bending	1415
C-H methyl sym. bending	1388	1387.1 w	1386.2 w
Ring C-H bending	1361	1306.2 w
Ring str.	1250	1258.1 w	1264.3 w
C-C bond between ring and methyl str.	1228
Ring C-H bending	1190	1180.2 w	1186.2 sh
C-H methyl rocking	1127, 1044	1116.9 s	1119.2 w
Ring out of plane bending	1030	1044.1 sh, 1019.1 sh	1048.5 w
Ring C=N str.	792	883.1 vs, 785.7 s, 738.7 m	891.1 s, 788.1 s
Ring C=N torsion	710	722.7 m	721.9 m
Ring bending	635, 540	676.6 s, 511.1 m	678.0 s, 630.3 sh, 568.4 sh, 513.8 sh
∂ C-C bond between ring and methyl	458	463.1 m	463.3 w
Terminal Mo=O64, 67, 68 str.		989.9 s	949.9 m

1, 3-Diaminopropane⁷⁴ shows N-H absorption bands in the range 3052-3351 cm^-1. Absorptions at 3427 cm^-1& 3014 cm^-1 suggest the presence of N-H group in [6] (Table-5). A strong band at 944 cm^-1 is attributed to terminal Mo=O^{64, 67, 68}stretching. NH₂ bending absorption in the range 1159 cm⁻¹-1182 cm⁻¹ is also shifted to lower wave number 1108 cm⁻¹, mainly due to coordination with molybdenum. Occurrence of terminal Mo=O is due to oxo abstraction^{59, 60} by molybdenum from THF.

Table 5: FTIR absorptions in cm⁻¹

Absorptions	1, 3-Diaminopropane74	[6]
N-H str.	3052–3351	3427.1 m, 3014.1 v s
CH2 str.	2873–2961	2898.3 sh, 2787.7 sh, 2701.1 sh
NH2 bending	1627	1609.1 s
CH2 deformation	1571–1582	1481.1 m, 1464.5 s, 1409.1
NH2 Bending	1159–1182	1193.2 m, 1108.2 m
C-N sym str.	1062	1031.3 sh
CH2 deformation	742, 841	887.1 s, 786.1 m
Mo-N		449.3 w
Terminal Mo=O64, 67, 68 str.		944.9 s

N-H stretching of pyrazole^{75, 76}occursat 3452 cm^-1. Band at 3386 cm^-1 reflects that [7] contains N-H group. N-H stretching is declined due to N→Mo coordination. Medium band at 969 cm^-1 shows the existence of terminal Mo=O^{64, 67, 68}in [7] (Table-6). Occurrence of terminal Mo=O is due to oxo abstraction^{59, 60} by molybdenum from THF.

Table 6: FTIR absorptions in cm⁻¹

Absorptions	Pyrazole75, 76	[7]
N-H,  str.	3452	3386.9 s
C-H str.	3153, 3142	3149.9 sh
C=C ring str.	1560	1631.0 m, 1519.0 sh
N-C  ring str.	1467, 1140	1474.5 w, 1402.2 sh, 1350.3 w
C-H in plane bending	1047, 1037	1126.0 w, 1052.2 w
C-H out of plane bending (wagging), ring twisting	891, 841, 762	777.0 m, 760.1 sh, 740.8 sh
Ring twisting	658, 620	675.4 sh, 605.2 sh, 581.8 sh
Mo-N		437.7 sh
Ring twisting, N-H wagging	501	518.7 w
Terminal Mo=O64, 67, 68 str.		969.6 m

1-Methylpyrrolidine^77-79shows strong C-H symmetric stretching at2971cm^-1 and C-H asymmetric stretching at2890 cm^-1, 2832 cm^-1, 2780 cm^-1. C-H asymmetric stretching of [8] is found at 2750 cm^-1. Weak band corresponding to the presence of terminal Mo=O^{64, 67, 68} str. is observed at 976 cm^-1 in [8] (Table-7). A peak at 3410 cm^-1 may be due to 1-methylpyrrolidinium cation. Occurrence of terminal Mo=O is due to oxo abstraction^{61, 62}by molybdenum from THF.

Table 7: FTIR absorptions in cm⁻¹

Absorptions	1-Methylpyrrolodine77-79	[8]
N+-H		3410.6 v s,
υs(C-H) str	2971 s
υas(C-H) str	2890 sh, 2832 m, 2780 s	2750.3 sh
(C-H) deformation	1450 s	1634.0 m, 1462.0 w
υ(C-C) str	1364 s	1383.7 sh
υ(C-N) str	1245 s, 1202 m, 1163 s, 1113 m	1108.6 w
(C-H) bending	1046 s	1004.6 sh
CH2 rocking	877 s	734.9 m b
CNC deformation	575 w
Terminal Mo=O64, 67, 68 str.		976.1 w

¹H NMR Spectra

Spectra were taken in DMSO-d₆solvent. Solvent residual peak ofDMSO-d₆⁸⁰occurs at 2.50 ppm.THF⁸⁰ spectrum in DMSO-d₆shows O-CH₂ peak and CH₂peak at 3.60 ppm and 1.76 ppm, respectively. In the spectra given below, ↑ and ↓ represent upfield/downfield shift.

Succinimide^{51, 53} CH₂ absorb at 2.73 ppm. Spectrum of [1]in DMSO-d₆ shows CH₂ absorption at 3.63 ppm showing downfield shift due to decrease in electron density around these protons on coordination with molybdenum through carbonyl group (Fig.-1, Table-8).

Figure 1: 1H-NMR of Mo2O2Cl2(C4H5NO2)2(C4H8O)2, [1]. Click here to View figure

Spectrum of [2]in DMSO-d₆ shows CH₂ absorption at 3.42 ppm showing downfield shift due to decrease in electron density around these protons on coordination with molybdenum through carbonyl group (Fig.-2, Table-8).

Figure 2: 1H-NMR of Mo2O3Cl5(C4H5NO2)2(C4H8O)2, [2]. Click here to View figure

Table 8: ¹H NMR absorptions in ppm

Assignments	Succinimide51, 53 in CDCl3	[1]	[2]
N-H	8.9	11.06 ↓	10.97 ↓
CH2	2.73	3.63 ↓	3.42 ↓
Residual80 DMSO-d6		2.54	2.48

 

1, 4-Diaminobutane⁸¹in H₂Oshows N-H peak at 1.15 ppm.NMR of [3] in DMSO-d₆suggests that NH₂ peak has shifted downfield. Peak of side CH₂ (attached to N which coordinates)as well as peak of middle CH₂ (attached to outer CH₂ on the side in which N coordinates)have shifted downfield due to decrease in electron density around these protons on N→Mo coordination (Fig.-3, Table-9).

Figure 3: 1H-NMR of Mo2O2Cl2(H2NCH2CH2CH2CH2NH2)2,[3]. Click here to View figure

Table 9: ¹H NMR absorptions in ppm

Assignments	1, 4-Diaminobutane81in H2O	[3]
NH2	1.14 4H	8.23 ↓
Side CH2 (attached to N which coordinates)	3.02-3.05 4H	3.52 ↓
Middle CH2 (attached to outer CH2 on the side in which N coordinates)	1.75-1.78 4H	2.66 ↓
Residual80 DMSO-d6		2.43

 

Comparisonof 3-methylpyridine^{71, 72, 82}spectrum withthat of [4], shows thatthere is downfield shift for all protons. This is due to reduction in ring π-electron density around these protons on sharing of lone pair by nitrogen with molybdenum (Fig.-4, Table-10).

Figure 4: 1H-NMR of Mo3Cl8(C6H7N)4(C4H8O)2,[4]. Click here to View figure

Further, in the spectrum of [5], it is found that there is downfield shift for all protons. This is due to reduction in ring π-electron density around these protons on sharing of lone pair by nitrogen with molybdenum (Fig.-5, Table-10).

Figure 5: 1H-NMR of Mo3O6Cl6(C6H7N)6,[5]. Click here to View figure

Table 10: ¹H NMR absorptions in ppm

Absorptions	3-Methylpyridine71, 72, 82  in CDCl3	[4]	[5]
H (CH3)	2.32 3H Singlet	3.27 ↓	2.56 ↓
H-C1	8.44 1H Singlet	8.77 ↓	8.80 ↓
H-C3	7.45 1H Doublet	8.40 ↓	8.23 ↓
H-C4	7.16 1H Triplet	7.92 ↓	7.82 ↓
H-C5	8.42 1H Doublet	8.70 ↓	8.74 ↓
Residual80 DMSO-d6		2.46	2.49
THF80 C-2, 5 (attached to N)		3.53
THF80 C-3, 4		1.69

 

Comparison of spectrum of 1, 3-diaminopropane⁸³ with that of [6] (Fig.-6, Table-11) in DMSO-d₆suggests that NH₂ and CH₂ absorptions of 1, 3-diaminopropane have downfield shift. This is because of decrease in electron density around these protons on N→Mo coordination.

Figure 6: 1H-NMR of MoO2Cl3(HNCH2CH2CH2NH2)2,[6] Click here to View figure

Table 11: ¹H NMR absorptions in ppm

Assignments	1, 3-Diaminopropane83in CDCl3	[6]
NH2	1.21 4H	7.89 ↓
Middle CH2	1.59 2H	2.87 ↓
Side CH2 (attached to N which coordinates)	2.76 4H	3.56 ↓
Residual80 DMSO-d6		2.50

 

Spectrum of pyrazole^{72, 84} in CCl₄ shows absorptions due to middle C-H proton at 6.31 ppm, C-H protons on other two carbons at 7.61 ppm and due to N-H proton at 12.64 ppm. Spectrum of [7] shows that all the pyrazole CH protons have moved downfield (Fig.-7, Table-12). This is because of decrease in electron density around these protons on N→Mo coordination. Due to keto-enol tautomerization equilibrium, peaks of CH protons of pyrazole appear as singlets.

Figure 7: 1H-NMR of Mo2O4Cl4(C3H4N2)4,[7] Click here to View figure

Table 12: ¹H NMR absorptions in ppm

Assignments	Pyrazole72, 84in CCl4	[7]
N-H	12.64 1H	9.42 ↑
Middle CH	6.31 (s) 1H	6.51 ↓
Side CH	7.61(s) 2H	7.96 ↓
Residual80 DMSO-d6		2.57

 

Spectrum of[8] shows that all the CH absorptions of 1-methylpyrrolidine⁷⁷ have moved downfield, referring to decline in electron density of the ring on N→Mo coordination (Fig.-8, Table-13). There is a broad peak at 11.10 ppm indicating formation of 1-methylpyrrolidinium ion.

Figure 8: 1H-NMR of Mo2O6Cl8(C5H11N)4, [8] Click here to View figure

Table 13: ¹H NMR absorptions in ppm

Assignments	1-Methylpyrrolidine77	[8]
N+-H		11.10
CH3	2.3 3H	3.43-3.51 ↓
C2-H & C5-H (attached to N)	2.5 4H	2.73-2.91↓
C3-H & C4-H	1.6 4H	1.85-1.98 ↓
Residual80 DMSO-d6		2.50

 

Spectra were taken in DMSO-d₆solvent. Solvent residual peak ofDMSO-d₆⁸⁰occurs at 39.52±0.06 ppm.THF⁸⁷ spectrum in DMSO-d₆shows O-CH₂ peak and CH₂peak at 67.03 ppm and 25.14 ppm, respectively. In the spectra given below, ↑ and ↓ represent upfield/downfield shift.

Spectrum of [3] shows that there is slight upfield shift of all absorptions of 1, 4-diaminobutane⁸⁵. This may be due to change of solvent from CDCl₃ to DMSO-d₆ (Fig.-9, Table-14).

Figure 9: 13C-NMR of Mo2O2Cl2(H2NCH2CH2CH2CH2NH2)2,[3] Click here to View figure

Table 14: ¹³C NMR absorptions in ppm

Assignments	1, 4-Diaminobutane85 in CDCl3	[3]
C attached to nitrogen	41	38.24↑
Other C	29	25.04↑
Residual80 DMSO-d6		39.50

 

Spectrum of [4] shows that there is slight upfield shift of C-2 and C-6 of 3-methylpyridine⁸⁶, whereas there is slight downward shift of C-3, C-4 and C-5. This is due to flow of π-electron density from C-3, C-4 and C-5 to N through C-2 and C-6, when N coordinates with Mo (Fig.-10, Table-15).

Figure 10: 13C-NMR of Mo3Cl8(C6H7N)4(C4H8O)2,[4] Click here to View figure

Table 15: ¹³C NMR absorptions in ppm

Assignments	3-Methylpyridine86 in CDCl3	[4]
C-2 (attached to CH3)	150.27	146.14 ↑
C-3	133.08	136.27 ↓
C-4	136.40	138.77 ↓
C-5	123.16	126.43 ↓
C-6	146.93	140.83 ↑
CH3	18.36	17.94 ↑
Residual80 DMSO-d6		39.42
THF87 C-2, 5 (attached to N)		65.88
THF87 C-3, 4		23.97

 

Spectrum of [7] shows that there is practically no change in chemical shift of pyrazole⁸⁸ on N→Mo coordination (Fig.-11, Table-16).

Figure 11: 13C-NMR of Mo2O4Cl4(C3H4N2)4,[7] Click here to View figure

Table 16: ¹³C NMR absorptions in ppm

Assignments	Pyrazole88 in CDCl3	[7]
Carbons attached to N atoms	134.0	133.12 ↑
Remaining carbon	105.1	104.81 ↑
Residual80 DMSO-d6		39.42

Spectrum of [8] shows that there is slight upfield shift of all absorptions of 1-methylpyrrolidine⁸⁹. This may be due to change of solvent from CDCl₃ to DMSO-d₆ (Fig.-12, Table-17).

Figure 12: 13C-NMR of Mo2O6Cl8(C5H11N)4, [8] Click here to View figure

Table 17: ¹³C NMR absorptions in ppm

Assignments	1-Methylpyrrolidine89 in CDCl3	[8]
C-1, C-4 (attached to N)	58.8	54.24 ↑
C-2, C-3	23.3	22.66 ↑
CH3	46.6	40.12 ↑
Residual80 DMSO-d6		39.42

 

Microbiological Activity

Molybdenum compounds prepared were tested using agar well diffusion assay methodfor their antibacterial and antifungal potential on the strains: Staphylococcus aureus (gram positive bacteria) (MTCC-737), E. coli (gram negative bacteria) (MTCC-1687), Candida albicans (fungus) (MTCC-227) and Aspergillus niger (fungus) (MTCC-282).Standard drugs amoxicillin and ketoconazole were used for bacteria and virus, respectively as reference.Zone of inhibition⁹⁰ for a strain of bacteria/fungi was estimated to ascertain the amount of resistance of bacteria/fungi to the drug used as reference.Molybdenum compounds synthesized have been noted as potentially active against the above said bacteria and fungi (Table-18). Especially,

Compounds 1, 2, 4, 5 and 8 have greater antibacterial activity against E. coli than the reference drug (amoxicillin).

Compounds 1, 2 and 5 have greater antifungal activity against C. albicans than the reference drug (ketoconazole).

Table 18: Microbiological Study

Compound (100 µg/ml)	Zone of inhibition90 (mm)
	Gram- positive	Gram- negative	Antifungal
	S. aureus	E. coli	C. albicans	A. niger
Reference Drug	25.69	18.35	21.37	28.21
[1]	24.12	19.56	21.74	21.56
[2]	19.28	22.51	23.12	21.58
[4]	19.84	22.21	19.52	21.69
[5]	21.54	49.62	21.47	19.87
[8]	23.11	22.61	19.85	18.72
Conclusion and results: These compounds can kill and inhibit the growth of microbes

 

Mass Spectra (LC-MS)

Theoretical m/z values of the fragments have been calculated⁹¹ on the basis of the most abundant isotopes of the individual elements. Fragments detected (Tables-19, 20) reinforce the formulae,

Table 19:  LC-MS Ionization. Click here to View table

Table 20: LC-MS Ion m/z values

Comp.	Fragment	Calculated91	Detected	Relative  intensity
[1]	[MoOCl2(C4H8O)2]+	327.95	324.17	30%
	[MoOCl2(C4H5NO2)2(C4H8O)]2+	226.97	230.08	58%
	[MoOCl3(C4H5NO2)2(C4H8O)]+	488.92	490.35	8%
	[MoO2Cl2]+	199.83	197.04	34
	[MoOCl2]2+	91.91	91.03	25
	[Mo2O2Cl5(C4H5NO2)2(C4H8O)2]2+	372.41	376.20	100%
	[MoO2Cl2(C4H5NO2)(C4H8O)2]+	442.99	448.25	10%
[2]	[MoOCl2]2+	91.91	91.04	100
	[C4H5NO2]+	99.03	100.05	21%
	[C4H8O]+	72.05	73.07	11%
	[MoOCl2(C4H5NO2)2(C4H8O)]2+	226.97	230.09	8%
	[MoOCl2(C4H5NO2)2(C4H8O)2]2+	263.00	263.13	52%
	[Mo2O2Cl2(C4H5NO2)2(C4H8O)2]2+	319.95	321.11	20%
	[MoO2Cl2(C4H5NO2)2(C4H8O)]+	469.95	471.24	12%
	[MoO2Cl2(C4H5NO2)2]+	397.89	397.23	18%
	[MoO2Cl2(C4H5NO2)]+	298.86	299.18	14%
	[MoO2Cl]+	164.86	163.10	15%
[3]	[MoO2Cl2]+	199.83	199.8	100%
	[MoO2Cl]+	164.86	164.90	40%
	[MoOCl]+	148.86	147.00	92%
	[MoO2]+	129.89	130.00	10%
	[H2NCH2CH2CH2CH2]+	72.08	71.0	22%
	[H2NCH2CH2CH2]+	58.06	59.0	36%
[4]	[C6H7N]+	93.05	94.07	44%
	[MoCl4]+	237.78	235.17	17%
	[MoCl4(C6H7N)]+	330.83	329.11	5%
	[Mo3Cl8(C6H7N)4]2+	472.84	472	1%
	[MoCl6(C6H7N)]+	400.77	400	3%
	[Mo3Cl8(C6H7N)4(C4H8O)2]2+	544.90	544.46	5%
	[Mo3Cl8(C6H7N)4(C4H8O)]2+	508.87	509.34	5%
	[C4H8O]+_	72.05	73.07	20%
[5]	[C6H7N]+	93.05	94.06	100
	[MoO2Cl3(C6H7N)]+	327.85	328.25	10%
	[MoO2Cl3(C6H7N)]2+	163.92	163.0	1%
	[MoO2Cl3(C6H7N)3]2+	256.98	256.18	5%
	[Mo3O2Cl3(C6H7N)4]2+	401.40	400.31	5%
	[Mo3O5Cl3(C6H7N)5]2+	471.94	472.38	3%
	[MoOCl2]2+	91.91	91.04	3%
	[Mo3O6Cl4(C6H7N)6]2+	543.95	545.49	2%
	[Mo3O6Cl6(C6H7N)6]2+	578.92	581.38	<1%
[6]	[MoO(HNCH2CH2CH2NH2)]+	186.97	187.00	15%
	[MoO(HNCH2CH2CH2NH2)]2+	93.48	93.10	60%
	[MoOCl(HNCH2CH2CH2NH2)]+	221.94	220.0	100.0%
	[H2NCH2CH2CH2]+	58.06	59.0	4%
[7]	[C3H4N2]+	68.03	69.05	100%
	[MoOCl2]2+	91.91	91.04	27%
	[MoO2Cl]+	164.86	163.11	24%
	[MoO2Cl3(C3H4N2)2]+	370.87	375.30	5%
	[MoO2Cl3]+	234.80	235.17	8%
	[Mo2O3Cl4(C3H4N2)2]+	519.74	519.42	3%
	[Mo2O3Cl2(C3H4N2)2]+	449.80	447.36	5%
[8]	[C5H11N]+	85.08	86.09	100%
	[MoOCl2]2+	91.91	91.04	3%
	[Mo2O3(C5H11N)2]2+	206.98	207.19	6%
	[Mo2O6Cl4(C5H11N)2]+	601.83	596.19	2%
	[MoO2Cl]+	164.86	163.12	2%
	[Mo2O5Cl4(C5H11N)]+	500.74	503.10	7%

 

Conclusion

Band at 3294 cm^-1 indicates that [1] contains succinimide N-H group. Bands at 980 cm^-1and 919 cm^-1support the availability of cis-MoO2²⁺core in [1]. Occurrence of cis-MoO₂²⁺ core is due to oxo abstraction by molybdenum from THF. There is decrease in C=O sym and asym absorptions due to decrease in C=O bond order on O→Mo coordination in [1]. Succinimide CH₂ absorb at 2.73 ppm. Spectrum of [1]shows CH₂ absorption at 3.63 ppm showing downfield shift due to decrease in electron density around these protons on coordination with molybdenum through carbonyl group. Microbiological studies reveal that [1] is effective against the bacteria/fungi tested for, especially E. coli and C. albicans, where [1] is more effective than the reference drugs themselves. Elemental analysis and LC-MS fragmentation support the proposed formula.

Band at 3433 cm^-1 indicates that [2] contains succinimide N-H group. Bands at 984 cm^-1and 923 cm^-1support the availability of cis-MoO2²⁺ core in [2]. Occurrence of cis-MoO₂²⁺ core is due to oxo abstraction by molybdenum from THF. There is decrease in C=O sym and asym absorptions due to decrease in C=O bond orderon O→Mo coordination in [2]. Spectrum of [2]shows CH₂ absorption at 3.42 ppm showing downfield shift due to decrease in electron density around these protons on coordination with molybdenum through carbonyl group. Microbiological studies reveal that [2] is effective against the bacteria/fungi tested for, especially E. coli and C. albicans, where [2] is more effective than the reference drugs themselves. Elemental analysis and LC-MS fragmentation support the proposed formula.

Strong 1, 4-diaminobutaneN-H absorptions have been recorded at 3391 cm^-1, 3077 cm^-1 and 3010 cm^-1 in [3]. Terminal Mo=O stretching occurs at 990 cm^-1 -1010 cm^-1 in various inert solvents. A medium Mo=O stretching at 921 cm^-1 conforms to the presence of terminal Mo=O group. There is a decline in Mo=O stretching to 921 cm^-1 showing Mo coordination to 1, 4-diaminobutane through N atom, in a direction trans to Mo=O bond. Bending mode due to NH₂ observed in 1, 4-diaminobutane at 1146 cm⁻¹ is declined to 1116 cm⁻¹, because of N→Mo coordination. 1, 4-Diaminobutaneshows N-H peak at 1.15 ppm.NMR of [3] suggests that NH₂ peak has shifted downfield. Peak of side CH₂ (attached to N which coordinates)as well as peak of middle CH₂ (attached to outer CH₂ on the side in which N coordinates)have shifted downfield due to decrease in electron density around these protons on N→Mo coordination. ¹³CNMR spectrum of [3] shows that there is slight upfield shift of all absorptions of 1, 4-diaminobutane . This may be due to change of solvent from CDCl₃ to DMSO-d₆. Elemental analysis and LC-MS fragmentation support the proposed formula.

Strong bands at 3119 cm^-1 and 3054 cm^-1 have been noticed in [4] which show presence of 3-methylpyridinering C-H absorptions. Ring C=N stretching & ring C=N torsion wave numbers have increased and ring C-H bending mode wave numbers have declined due to Mo(dπ)→N(pπ) back bonding. A strong band at 989 cm^-1 revealsthe presence of terminal Mo=O in [4].Comparisonof 3-methylpyridinespectrum withthat of [4], shows thatthere is downfield shift for all protons. This is due to reduction in ring π-electron density around these protons on sharing of lone pair by nitrogen with molybdenum.¹³C NMR spectrum of [4] shows that there is slight upfield shift of C-2 and C-6 of 3-methylpyridine, whereas there is slight downward shift of C-3, C-4 and C-5. This is due to flow of π-electron density from C-3, C-4 and C-5 to N, through C-2 and C-6, when N coordinates with Mo. Microbiological studies reveal that [4] is effective against the bacteria/fungi tested for, especially E. coli where [4] is more effective than the reference drug itself. Elemental analysis and LC-MS fragmentation support the proposed formula.

Strong band at 3391 cm^-1 has been noticed in [5] which shows presence of 3-methylpyridinering C-H absorption. Ring C=N stretching & ring C=N torsion wave numbers have increased and ring C-H bending mode wave numbers have declined due to Mo(dπ)→N(pπ) back bonding. A medium band at 949 cm^-1 reveals the presence of terminal Mo=O group in [5].Comparison of 3-methylpyridine spectrum with that of [5], shows thatthere is downfield shift for all protons. This is due to reduction in ring π-electron density around these protons on sharing of lone pair by nitrogen with molybdenum. Microbiological studies reveal that [5] is effective against the bacteria/fungi tested for, especially E. coli and C. albicans, where [5] is more effective than the reference drugs themselves. Elemental analysis and LC-MS fragmentation support the proposed formula.

Absorptions at 3427 cm^-1& 3014 cm^-1 in [6] suggest the presence of 1, 3-diaminopropane N-H group in the compound. A strong band at 944 cm^-1 is attributed to terminal Mo=O stretching. NH₂ bending absorption in the range of 1159 cm⁻¹-1182 cm⁻¹ is also shifted to lower wave number 1108 cm⁻¹, mainly due to coordination with molybdenum. Occurrence of terminal Mo=O is due to oxo abstraction by molybdenum from THF. Comparison of spectrum of 1, 3-diaminopropane with that of [6]suggests that NH₂ and CH₂ absorptions of 1, 3-diaminopropane have downfield shift. This is because of decrease in electron density around these protons on N→Mo coordination. Elemental analysis and LC-MS fragmentation support the proposed formula.

Band at 3386 cm^-1 reflects that [7] contains pyrazole N-H group. N-H stretching is declined due to Mo-N coordination. Medium band at 969 cm^-1 shows the existence of terminal Mo=O in [7]. Occurrence of terminal Mo=O is due to oxo abstraction by molybdenum from THF. Spectrum of pyrazole shows absorptions due to middle C-H proton at 6.31 ppm, C-H protons on other two carbons at 7.61 ppm and due to N-H proton at 12.64 ppm. Spectrum of [7] shows that all the pyrazole CH protons have moved downfield. This is because of decrease in electron density around these protons on N→Mo coordination. Due to keto-enol tautomerization equilibrium, peaks of CH protons of pyrazole appear as singlets.¹³ C NMR spectrum of [7] shows that there is practically no change in chemical shift of pyrazole. Elemental analysis and LC-MS fragmentation support the proposed formula.

Absorption at 2750 cm^-1 in [8] shows the presence of 1-methylpyrrolidine C-H asymmetric stretching. Weak band corresponding to the presence of terminal Mo=O is observed at 976 cm^-1. A peak at 3410 cm^-1 may be due to 1-methylpyrrolidinium cation. Occurrence of terminal Mo=O is due to oxo abstraction by molybdenum from THF. Spectrum of[8] shows that all the CH absorptions of 1-methylpyrrolidinehave moved downfield, referring to decline in electron density of the ring on N→Mo coordination. There is a broad peak at 11.10 ppm indicating formation of 1-methylpyrrolidinium ion.¹³C NMR spectrum of [8] shows that there is slight upfield shift of all absorptions of 1-methylpyrrolidine. This may be due to change of solvent from CDCl₃ to DMSO-d₆. Microbiological studies reveal that [8] is effective against the bacteria/fungi tested for, especially E. coli where [8] is more effective than the reference drug itself. Elemental analysis and LC-MS fragmentation support the proposed formula.

Acknowledgement

We, the authors thank P. U. Chandigarh, India for providing facility of elemental analysis and spectral studies. We are also thankful to ISF Analytical Laboratory (ISF College of Pharmacy), Ferozepur Road, Moga, Punjab (India) for carrying out microbiological studies.

Conflict of Interest

There is no conflict of interest among the authors.

References

1. Shetgiri, N. P.; Nayak,B. K., Indian J. Chem., 2005, 44B, 1933-1936.
2. Aeberli,   P;  Go gerty,  J. H;  Houlihan,  W. J;  Iorio,  L. C., J. Med. Chem.,1976, 19(3),  436-438.
   CrossRef
3. Pennington, F. C.; Guercio, P. A.; Solomons, I. A., J. Amer. Chem. Soc., 1953, 75(9), 2261.
   CrossRef
4. Hall, I. H.; Wong, O. T.; Scovill, J. P., Biomed Pharmacother, 1995, 49(5), 251-258.
   CrossRef
5. Crider, A. M; Kolczynski, T. M.; Yates,  K. M., J. Med. Chem.,1980, 23(3), 324-326.
   CrossRef
6. Johnston, T. P.; Piper, J. R.; Stringfellow, C. R., J. Med. Chem., 1971, 14(4), 350-354.
   CrossRef
7. Kaczorowski, G. J.; McManus, O. B.; Priest, B. T.; Garcia, M. L., Gen. Physiology, 2008, 131(5), 399-405.
   CrossRef
8. Musso, D. L.; Cochran, F. R.; Kelley, J. L.; McLean, E. W.; Selph, J. L.; Rigdon, G. C., J. Med. Chem., 2003, 46(3), 399-408.
   CrossRef
9. Rich, D. H.; Gardner, J. H., Tetrahedron Letters, 1983, 24(48), 5305-5308.
   CrossRef
10. Zentz, F.; Valla, A.; Guillou, R. L.; Labia, R.; Mathot, A. G.; Sirot, D., Farmaco, 2002,   57(5), 421-426.
    CrossRef
11. Correa, R.; Filho, V. C.; Rosa, P. W.; Pereira, C. I.; Schlemper, V.; Nunes, R. J., Pharm. Pharmacol. Comm., 1997, 3(2), 67-71.
12. Kornet, M. J.; Crider, A. M.; Magarian, E. O., J. Med. Chem., 1977, 20(3), 405-409.
    CrossRef
13. Isaka, M.; Prathumpai, W.; Wongsa, P.; Tanticharoen, M.; Hirsutellone, F., Org. Lett.,2006, 8(13), 2815-2817.
    CrossRef
14. Filho, V. C.; Nunes, R. J.; Calixto, J. B.; Yunes, R. A., Pharm. Pharmacol. Comm., 1995, 1(8), 399-401.
15. Hazra, B. G.; Pore, V. S.; Day, S. K.; Datta, S.; Darokar, M. P., Saikia, D., Bioorg. Med. Chem. Lett., 2004, 14(3), 773-777.
    CrossRef
16. Amah, K. U.; Sylvain, A. Y. G.; Gaston, K. A.; Alice, K. H. M. T.; Baptiste,M. J.,International Research Journal of Pure & Applied Chemistry, 2016, 12(4), 1-11.
    CrossRef
17. Gao, S.; Wang, J.; Xu, S.; Li, H.; Chen, K.; Ouyang, P., Chinese Journal of Chemical Engineering, 2021, 30, 4-13.
    CrossRef
18. Gaymans, R. J.; Utteren, T. E. C.; van den Berg, J. W. A.; Schuyer, J., Journal of Polymer Science: Polymer Chemistry Edition, 1977, 15(3), 537-545.
    CrossRef
19. Pasupathy, A.; Nirmala, S.; Abirami, G.; Satish, A.; Milton, R. P., International Journal of Scientific and Research Publications, 2014, 4(3), 1-3.
20. Stellman, J. M., Encyclopaedia of Occupational Health and Safety, 4^th Edition, International Labour Office, Geneva, 1998, 4.
21. Shimizu, S.; Watanabe, N.; Kataoka, T.; Shoji, T.; Abe, N.; Morishita, S.; Ichimura. H., Ullmann’s Encyclopedia of Industrial Chemistry, 2002, doi:10.1002/14356007.a22_399.
    CrossRef
22. Sims, G. K.; Sommers, L. E., Environmental Toxicology and Chemistry, 1986, 5, 503-509.
    CrossRef
23. Sims, G. K.; Sommers, L. E., J. Environmental Quality, 1985, 14, 580-584.
    CrossRef
24. Srinivasu, J. V.; Narendra, K.; Rao, B. S., Indian Journal of Pure & Applied Physics, 2017, 55, 797-805.
25. Bingham, E.; ‎ Cohrssen, B., Patty’ Toxicology, John Wiley & Sons, 6^th Edition, 2012, 1.
26. Chae, T. U.;  Kim, W. J.;  Choi, S.;  Park, S. J.;  Lee, S. Y., Scientific Reports, 2015, 5, article 23040, 1-13.
    CrossRef
27. Abebe, A.; Bayeh, Y.; Belay, M.; Gebretsadik, T.;  Thomas, M.;  Linert, W., Future Journal of Pharmaceutical Sciences, 2020, 6, Article No. 13, 1-9.
    CrossRef
28. Salim, E. I.; Wanibuchi, H.; Morimura, K.; Kim, S.; Yano, Y.; Yamamoto, S.; Fukushima S., Carcinogenesis, 2000, 21(2), 195-203.
29. J. E. Seely; Pegg, A. E., Biochem. J., 1983, 216, 701-707.
    CrossRef
30. Barcelo, M.; Ravina, E.; Masaguer, C. F.;  Dominguez, E.;  Areias, F. M.; Brea, J., Bioorg. Med. Chem. Lett.,2007, 17, 4873-4877.
    CrossRef
31. Pospisil, P.; Folkers, G.;  FABAD J. Pharm. Sci.,2004, 29, 81-92.
32. Cho, A. E.; Guallar, V.; Berne, B. J.; Friesner, R., J. Computchem.,2005, 26, 915-931.
    CrossRef
33. Bekhit, A. A.; Ashour, H. M. A.; Ghang, Y. S. A.; Bekhit, A. E. A.; Baraka, A., Eur. J. Med. Chem., 2008,43, 456-463.
    CrossRef
34. Aziz, M. A.; Abuorahma, G. E. A.; Hassan, A. A.,  Eur. J. Med. Chem.,2009, 44, 3480-3487.
    CrossRef
35. Ahmed, O. M.; Muhamed, M. A.; Ahmed, R. R.; Ahmed, S. A., Eur. J. Med. Chem., 2009, 44, 3519-3523.
    CrossRef
36. Frigola, J.;  Colombo, A.; Pares, J.; Martinez, L.; Sagarra, R.; Rosert, R., Eur. J. Med. Chem., 1989,24, 435-445.
    CrossRef
37. Bondock, S.; Rabie, R.; Etman, H. A.; Fadda, A. A., Eur. J. Med. Chem.,2008, 43, 2122-2229.
    CrossRef
38. Castagnolo, D.; Mantti, F.; Radi, M.; Bechi, B.; Pagano, M.; Logu, A. D., Bioorg. Med. Chem., 2009,17, 5716-5721.
    CrossRef
39. Gopalakrishnan, S.; Ravi, T. K.; Manojkumar, P., Eur. J. Med. Chem.,2009, 44, 4690-4694.
    CrossRef
40. Bekhit, A. A.; Aziem, T. A.,  Bioorg. Med. Chem., 2004, 12, 1935-1945.
    CrossRef
41. Richardson, C. H.; Shepard, H. H., Journal of Agricultural Research, 1930, 40(11), 1007-1015.
42. Page, N.; Stevenson, R.; Powell, M., Analytical Methods, 2014, 6(4), 1248-1253. 
    CrossRef
43. Abebe, A.; Hailemariam, T., Bioinorganic Chemistry and Applications, 2016, Article ID 3607924, 1-9.
    CrossRef
44. Thomas, D. D.; Ridnour, L. A.; Isenberg, J. S.; Flores, S. W.; Switzer, C. H.; Donzelli, S.; Hussain, P.; Vecoli, C.; Paolocci, N.; Ambs, S.; Colton, C. A.; Harris, C. C.; Roberts, D. D.; Wink, D. A., Free Radical Biology and Medicine, 2008, 45(1), 18-31.
    CrossRef
45. Chen, P. R.; He, C., Current Opinion in Chemical Biology, 2008, 12(2), 214-21.
    CrossRef
46. Pennella, M. A.; Giedroc, D. P., Biometals, 2005, 18(4), 413-28.
    CrossRef
47. Cowan, J. A.; Bertini, I.; Gray, H. B.; Stiefel, E. I.; Valentine, J. S.,
    Structure and Reactivity: Biological Inorganic Chemistry, 3, University Science Books, Sausalito, 2007, 8(2): 175181.
48. Jameel, A.; MSA, S. A. P., Asian Journal of Chemistry, 2010, 22(12), 3422-48.
49. Anupama, B.; Sunuta, M.; Leela, D. S.; Ushaiah; Kumari, C. G., Journal of Fluorescence, 2014, 24(4), 1067-76.
    CrossRef
50. Singh, G.; Mangla, V.; Goyal, M.; Singla, K.; Rani, D., American International Journal of Research in Science, Technology, Engineering & Mathematics, 2014, 8(2), 131-136.
51. Singh, G.; Mangla, V.; Goyal, M.; Singla, K.; Rani, D., American International Journal of Research in Science, Technology, Engineering & Mathematics, 2015,10(4), 299-308.
52. Singh, G.; Mangla, V.; Goyal, M.; Singla, K.; Rani, D., American International Journal of Research in Science, Technology, Engineering & Mathematics, 2015,11(2), 158-166.
53. Singh, G.; Mangla, V.; Goyal, M.; Singla, K.; Rani, D.; Kumar, R., American International Journal of Research in Science, Technology, Engineering & Mathematics, 2016, 16(1), 56-64.
54. Singh, G.; Kumar, R., American International Journal of Research in Science, Technology, Engineering & Mathematics, 2018, 22(1), 01-08.
55. Rani, D.; Singh, G.; Sharma, S., Oriental Journal of Chemistry, 2020, 36(6), 1096-1102.
    CrossRef
56. Singh, G.; Mangla, V.; Goyal, M.; Singla, K.; Rani, D., International Congress on Chemical, Biological and Environmental Sciences,2015, 930-942, May 7-9, Kyoto (Japan).
57. Rani, D.; Singh, G.; Sharma, S., Oriental Journal of Chemistry, 2021, 37(1), 46-52.
    CrossRef
58. Rani, D.; Singh, G.; Sharma, S., Oriental Journal of Chemistry, 2021, 37(2), 459-466.
    CrossRef
59. Planinic, P.; Meider, H.; Yeh, H.; Vikic-Topic, D., J. Coord. Chem., 1992, 25, 193-204.
    CrossRef
60. Behzadi, K.; Baghlaf, A. O.; Thompson, A., J. Less Common Metals, 1978, 57, 103-110.
    CrossRef
61. Vogel, A. I.,  A Text Book of Quantitative Inorganic Analysis; John Wiley and Sons: New York, (Standard methods), 1963.
62. Stamboliyska, B. A.; Binev, Y. I.; Radomirska, V. B.; Tsenov, J. A.; Juchnovskiet, I. N., Journal of Molecular Structure, 2000, 516, 237-245.
    CrossRef
63. Uno, T.; Machida, K., Bulletin of the Chemical Society of Japan, 1962, 35(2),276-283.
    CrossRef
64. Heyn, B.; Hoffmann; Regina, Z. Chem.,1976, 16, 407.
    CrossRef
65. Abramenko, V. L.; Sergienko, V. S.; Churakov, A.V., Russian J. Coord. Chem., 2000, 26(12), 866-871.
    CrossRef
66. Ergu¨ N. Kasap; Su¨ Leyman; O¨ Zceli´K., J. Inclusion Phenomena and Molecular Recognition in Chem., 1997, 28, 259-267.
    CrossRef
67. Barraclough, C. G.; Kew, D. J., Australian J. Chem., 1970, 23, 2387-2396.
    CrossRef
68. Ward, B. G.; Stafford, F. E., Inorg. Chem.,1968,7, 2569.
    CrossRef
69. Abramenko, V. L.; Sergienko, V. S., Russian J. Inorg. Chem., 2009, 54(13), 2031-2053.
    CrossRef
70. Toco’n, I. L.; Woolley, M. S.; Otero, J. C.; Marcos, J. I., Journal of Molecular Structure, 1998,470, 241-246.
    CrossRef
71. Gupta, S. K.; Srivastava, T. S., J. Inorganic and Nuclear Chem., 1970, 32, 1611-1615.
    CrossRef
72. Hossain, A. G. M. M.; Ogura, K., Indian J. Chem., 1996, 35A, 373-378.
73. Brewerp, D. G.; Wong, P. T. T.; Sears, M. C., Canadian J. Chem., 1968, 46(20), 3119-3128.
    CrossRef
74. Yadav, S.; Moheman, A.; Siddiqi, K. S., Arabian Journal of Chemistry, 2016, 9, suppliment 2, S1747-S1754.
    CrossRef
75. Stamboliyska, B. A.;  Binev, Y. I.; Radomirska, V. B.; Tsenov, J. A.; Juchnovski, I. N., Journal of Molecular Structure,2000,516, 237-245.
    CrossRef
76. Uno, T.; Machida, K.,Bulletin of the Chemical Society of Japan, 1962, 35(2), 276-283.
    CrossRef
77. Hoa, N. V.; Tuan, N. A.; Thao, P. T.; Huyen, T. T. T., Journal of Science and Technology, 2016, 54(2), 231-237.
78. Wang, G. T.; Mui. C.; Tannci, J. F.; Filler, M. A.; Musgrave, C. B.; Bent, S. F., J. Phys. Chem., B, 2003, 107, 4982-4996.
    CrossRef
79. Szafran, M.; Koput, J.; Szafran, Z. D.; Kwiatkowski, J. S., Vibrational Spectroscopy., 2000, 23, 1-11.
    CrossRef
80. Gottlieb, H. E.: Kotlyar, V.; Nudelman, A., J. Org. Chem., 1997, 62, 7512-7515.
    CrossRef
81. Olmo, C.; Casas, M. T.; Martínez, J. C.; Franco, Puiggalí, L.; J., Polymers, 2019, 11(4), 572, 1-19.
    CrossRef
82. Kumari, N.; Sharma, M.; Das,, P.; Dutta, D. K., Applied Organomet. Chem., 2002, 16, 258-264.
    CrossRef
83. Chatterjee, C.; Phulambrikar, A.; Das, S., J. Coord. Chem., 1990, 21(3), 231-236.
    CrossRef
84. Editor: Teresa M. V. D. Pinho e Melo, Recent Research Developments in Heterocyclic Chemistry,: 397-475 ISBN: 81-308-0169-8, 2007.
85. https://spectrabase.com/compound/GhReRxNt2Lp#9R7ID3SyH4X.
86. https://www.chemicalbook.com/SpectrumEN_108-99-6_13CNMR.htm.
87. Babij, Ni. R.; E. O.; McCusker, Whiteker, G. T.;Canturk, B.; Choy, N.; Creemer, L. C.; Amicis, C. V. D.; Hewlett, N. M.; Johnson, P. L.; Knobelsdorf, J. A.; Li, F.; Lorsbach, B. A.; Nugent, B. M.; Ryan, S. J.; Smith, M. R.; Yang, Q., Org. Process Res. Dev., 2016, 20, 661-667.
    CrossRef
88. Begtrup, M.; Boyer, G.; Cabildo, P.; Cativiela, C.; Claramunt, R. M.; Elguero, J.;  Garcia, J. I.; Toiron, C.; Vedser, P., Magnetic Resonance in Chemistry, 1993, 31, 107-168.
    CrossRef
89. http://www.molbase.com/en/hnmr_120-94-5-moldata-22594.html.
    CrossRef
90. Bhattacharjee, M. K., The Journal of Antibiotics, 2015, 68, 657-659.
    CrossRef
91. Audi, G.; Wapstra, A. H., Nucl. Phys. A. 1995, 595, 409-480.
    CrossRef

---

This work is licensed under a Creative Commons Attribution 4.0 International License.