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

It has been reported that molybdenum may extract 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, in THF medium using equimolar/bimolar quantities of the ligand, at normal temperature. The products thus obtained are: Mo2O3Cl5(C4H5NO2)2(C4H8O)2,[1]; Mo2O2Cl2(C4H5NO2)2(C4H8O)2,[2]; MoO2Cl2(HNCH2CH2CH2CH2NH2)2,[3]; Mo3Cl8(C6H7N)4(C4H8O)2, [4]; Mo3Cl6(C6H7N)6(C4H8O)6,[5]; MoO2Cl3(HNCH2CH2CH2NH2)2,[6]; Mo2O4Cl4(C3H4N2)4, [7] and Mo2O6Cl8(C5H11N)4, [8]. There is oxygen abstraction by molybdenum during the reaction from the oxygen containing solvent THF. Formulations of these compounds were made and their properties were studied with FTIR (transmission mode), 1H NMR/13C NMR, microbiological studies, elemental analysis (Mo, Cl, C, H, N) and LC-MS. All preparations, separations and isolations were executed in vacuum line and inert atmosphere (dry nitrogen) to eliminate any oxidation/hydrolysis of products by air/moisture. The formulations proposed have been supported by the above characterization studies.

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 bonds 16 . 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][18][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 H 2 SO 4 .

1,3-Diaminopropane
1, 3-Diaminopropane 26 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 used 27 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.

1-Methylpyrrolidine
1-Methylpyrrolidine 41 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 cefepime 42 : broad-spectrum cephalosporin antibiotic capable to treat bacteria causing pneumonia, infections of the skin and urinary tract.
Tr a n s i t i o n m e t a l s c o m p l e x e s o n coordination with ligands undergo 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][45][46][47][48][49] .
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/1,4diaminobutane/3-methylpyridine/1,3-diaminopropane/ pyrazole/1-methylpyrrolidine with MoCl 5 /MoO 2 Cl 2 have been carried out. Formulations of these compounds were made and their properties were studied with FTIR, 1 1-methylpyrrolidine, MoCl 5 and MoO 2 Cl 2 were 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 MoCl 5 /MoO 2 Cl 2 solution in THF taken in 100 mL round bottom flask. The reaction was carried out for about 7 hours. The products were isolated after filtration through filtration unit fitted with G-4 sintered glass crucible.
Oxinate gravimetric method 61 was used for molybdenum 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 hours. at 400ºC. 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 MoO 2 (C 9 H 6 NO) 2 .
Estimation of chlorine was carried out gravimetrically as silver chloride 61 . 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 AgNO 3 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 recording 1 H/ 13 C NMR in DMSO-d 6 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 method for their antibacterial and antifungal potential on the strains: Staphylococcus aureus (Gram-positive bacteria) (

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

FTIR Spectra
N-H stretching of succinimide 62,63 have been noted at 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-MoO 2 2+ core 64,65 in [1]. Occurrence of cis-MoO 2 2+ 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 coordination 16 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-MoO 2 2+ core 64,65 in [2]. Occurrence of cis-MoO 2 2+ 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 coordination 16 in [2] (Table-2).   [5] ( Table 4). Occurrence of terminal Mo=O is due to oxo abstraction 59,60 by molybdenum from THF. stretching. NH 2 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 6). Occurrence of terminal Mo=O is due to oxo abstraction 59,60 by molybdenum from tetrahydrofuran.  (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 tetrahydrofuran.  [1] in DMSO-d 6 shows CH 2 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).
Spectrum of [2] in DMSO-d 6 shows CH 2 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).  [3] in DMSO-d 6 suggests that NH 2 peak has shifted downfield. Peak of side CH 2 (attached to N which coordinates) as well as peak of middle CH 2 (attached to outer CH 2 on the side in which N coordinates) have shifted down field due to decrease in electron density around these protons on N→Mo coordination (Fig. 3, Table 9). Comparison of 3-methylpyridine 71,72,82 spectrum with that of [4], shows 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. 4, Table 10).
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). Comparison of spectrum of 1, 3-diaminopropane 83 with that of [6] (Fig. 6, Table 11) in DMSO-d 6 suggests that NH 2 and CH 2 absorptions of 1,3-diaminopropane have downfield shift. This is because of decrease in electron density around these protons on N→Mo coordination. Spectrum of pyrazole 72,84 in CCl 4 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. Spectrum of [8] shows that all the CH absorptions of 1-methylpyrrolidine 77 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.  occurs at 39.52 ± 0.06 ppm. THF 87 spectrum in DMSO-d 6 shows O-CH 2 peak and CH 2 peak at 67.03 ppm and 25.14 ppm, respectively. In the spectra given below, ↑ and ↓ represent upfield/ downfield shift.
Spectrum of [4] shows that there is slight upfield shift of C-2 and C-6 of 3-methylpyridine 86 , 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).  Spectrum of [7] shows that there is practically no change in chemical shift of pyrazole 88 on N→Mo coordination (Fig. 11, Table 16). Spectrum of [8] shows that there is slight upfield shift of all absorptions of 1-methylpyrrolidine 89 . This may be due to change of solvent from CDCl 3 to DMSO-d 6 (Fig. 12, Table 17).

Fig. 11. 13 C-NMR of Mo 2 O 4 Cl 4 (C 3 H 4 N 2 ) 4 , [7]
Microbiological Activity Molybdenum compounds prepared were tested using agar well diffusion assay method for 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 inhibition 90 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 and 5 have greater antifungal activity against C. albicans than the reference drug (ketoconazole).

Mass Spectra (LC-MS)
Theoretical m/z values of the fragments have been calculated 91

CONCLUSION
Band at 3294 cm -1 indicates that [1] contains succinimide N-H group. Bands at 980 cm -1 and 919 cm -1 support the availability of cis-MoO 2 2+ core in [1]. Occurrence of cis-MoO 2 2+ 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 CH 2 absorb at 2.73 ppm. Spectrum of [1] shows CH 2 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 -1 and 923 cm -1 support the availability of cis-MoO 2 2+ core in [2]. Occurrence of cis-MoO 2 2+ 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 [2]. Spectrum of [2] shows CH 2 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.  [3] suggests that NH 2 peak has shifted downfield. Peak of side CH 2 (attached to N which coordinates) as well as peak of middle CH 2 (attached to outer CH 2 on the side in which N coordinates) have shifted down field due to decrease in electron density around these protons on N→Mo coordination. 13 C NMR 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 CDCl 3 to DMSO-d 6 . 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] [4]. Comparison of 3-methylpyridine spectrum with that of [4], shows 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. 13 C 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-methylpyridine ring 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 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. 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. NH 2 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 NH 2 and CH 2 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 presence of 1-methylpyrrolidine C-H asymmetric the 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-methylpyrrolidine have 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. 13 C 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 CDCl 3 to DMSO-d 6 . 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.