Mono antimicrobial properties as well as antitumor

Mono and Diorganoantimony compounds –A Review Abstract: The chemistry of both mono and di-organometallic compounds of antimony has been reviewed. Synthesis and structure of their compounds have been described. Introduction: Antimony complexes have been used in the field of medicine and cosmetics.1,2 For the treatment of various parasitic diseases antimony containing compounds are commonly used.

For example, sodium antimony(V) gluconate is being used as a drug.3 Due to the fascinating structural diversity varying from discrete monomeric molecular species to supramolecular assemblies the chemistry of organoantimony(V) complexes has attracted significant attention in recent times.4 Similar to that of cis-platin, organoantimony derivatives also exhibit significant antimicrobial properties as well as antitumor activities5 which is associated with cytostatic activity.

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6 The biological toxicity of Sb is less than Pt and Pd based anticancer substances. In addition, organoantimony derivatives also show important functions as biocides, fungicides, catalyst components and antioxidants. Antimony in the oxidation state of +5 is interesting considering its hypervalent nature.7 In organic synthesis organoantimony(V) compounds have been used either as reagents or as catalysts extensively.8 Biological activity: Antimonials Since 1913, has been used in the field of therapeutic agent with the introduction of Sb(III) potassium tartarate in the treatment of leishmaniasis.

Pentavalent antimonials have replaced trivalent antimonials due to less toxic nature of Sb(V) compounds such as meglumine antimoniate for treating diseases. Meglumine antimoniate is recommended by WHO as a first choice medicine for leishmaniasis therapy.9 Bayer in 1915 introduced the first organometallic fungicides Upsulun which is an organomercurial compound. Since organomecurial compounds are environment unfriendly, Beiter and Leebrick 1963 chose a series of tri and pentavalent organoantimony and organobismuth compounds and examined their activity against fungicides.

It was found that organoantimony are moderately fungitoxic and more effective than organobismuth compounds. Burrell and Corke in 1980 studied the fungitoxicity of organo antimony compounds and found that fungal toxicity activity increased with increasing the molecular weight of organic compound attached to group VA element.102 Cristian Silvestru et al investigated the organoantimony(III) derivatives of dithiophosphorus ligand which were found to shows antitumor properties in both in vitro and in vivo studies.11 Cytotoxic activity to vascular endothelical cell was diminished when they replaced the bismuth atom by antimony atom in 2-(N,N-dimethylaminomethyl)phenylbis(4-methyl phenyl)bismuthane (DAPBi).12 (C6F5)2SbPh shows antifungal, antibacterial and insecticidal activities.

This compound has also been used as pesticide and insecticide for plant diseases as reported by R. Kant et al. Later the group also synthesized the diaryl antimony(III) amide which exhibits antitumor activity against mammary cancer cell line and human breast adenocarcinoma cell line.

In addition it also shows antibacterial activity against Pseudomonas aeruginosa, Staphylococcus aureus, and Klebsiela pneumonia. It exhibits significant antifungal properties against Aspergillus flavus and Aspergillus niger.13 Organoantimony(V) derivatives from Schiff bases exhibits higher antimicrobial activity than organoantimony(III) derivatives against Aspergillus flavus and Escherichia coli.

14 Potent antimicrobial properties are revealed in three discrete organoantimony(III) containing heteropolytungstates which was recently documented by U. Kortz et al.15 Organostibonic acids have also been used as potential anticancer agents, which inhibits the DNA binding16a,b group of B-ZIP proteins at micromolar concentration have been recently reported by Vinson et al.16c-e Monoorganoantimony Compounds: Monoorganoantimony(V) halides, due to their unstable nature, structural aspects of mono-alkyl and arylantimony(V) chlorides are not fully understood.17 For example at room temperature phenylantimony tetrachloride tends to disproportionate. Monoalkylantimony tetrachlorides also undergoes decomposition ready. Scheme 1 In order to stabilize the monoorganoantimony(V) chlorides, addition of neutral oxo donor ligands have been used which stabilize the compound at room temperature.

On the basis of spectral analysis such as IR and 1H NMR it was suggested that the antimony atom is3 hexacoordinated. In solution state, CH3SbCl4·L (L = PyO or 4-CH3PyO) exists as monomer in cis and trans forms. Above 70 ?C CH3SbCl4.L, it undergo decomposition giving rise to CH3Cl and SbCl3L.18 ?-diketones derivatives: Monoorganoantimony (acetylacetonato) trichlorides have been synthesized either by the reactions of phenylstibonic acid in HCl or monoorganoantimony(V) chloride with acetylacetone at low temperature condition.19 In solution state, monoorganoantimony(acetylacetonato) trichlorides are monomeric. The IR spectra reveal that these compounds show acetylacetone bidentate ligation.

On the basis of the observed doublet and singlet for acetylacetone-CH3 in the 1H NMR spectra, Okawara and co-workers have suggested an asymmetric octahedral structure for PhSb(acac)Cl3 and a symmetric structure for MeSb(acac)Cl3 in which methyl group occupys an axial position (Figure 1). Kawasaki et al have studied 1H NMR for PhSb(acac)Cl3 which shows asymmetric octahedral structure were the phenyl group occupies an equatorial position. For MeSb(acac)Cl3 the magnitude of the separation between methyl resonance increases in aromatic solvents indicating an enhancement in the non-equivalance of two acetylacetone-CH3 groups as a result of the aromatic ring current effect on asymmetrically solvated solute molecule. The dipole moment data also supports the asymmetric geometry for these compounds. Later the single crystal X-ray diffraction analysis of MeSb(acac)Cl3 support the asymmetric structure with distorted octahedral geometry.

20 Figure 1: Asymmetric structure of an MeSb(acac)Cl3 The three-membered organoantimony ring cyclo-Sb3R3 R = (Me3Si)2CH21a was prepared by Breunig and co-workers by reaction of RSbCl2 with Li3Sb at -40 °C. The alkyl groups are occupying cis and trans positions. The cis-trans positions of the substituents are4 identified by 1H and 13C NMR spectra in solution state. The three antimony atoms present almost resemble an equilateral triangular motif (Scheme 2).

Scheme 2 Polyoxometalates: The first organoantimony-containing POM {PhSbOH}3(A-?-PW9O34)29-, is a sandwich-type tungstophosphate which is dimeric in nature (Figure 2). The polyanion can be synthesized by the direct interaction of diphenylantimony trihalide with three different lacunary tungstophosphate precursors, Na9(A-?-PW9O34, K7PW11O39, or K10P2W20O70(H2O)2, in an aqueous acidic medium under hydrothermal conditions. The cluster formation takes place by removal of one of the phenyl group during its reaction with diphenylantimony trihalide.21b Figure 2: Molecular structure of {PhSbOH}3(A-?-PW9O34)29- Diorganoantimony Compounds: Synthesis of diphenylantimony trichloride:5 Diorganoantimony(V) halides have been synthesized by treating antimony(III) chlorides with diazonium salts or by halogenations of diorganoantimony(III) halides R2SbX with X2 (X = Cl, Br) (Scheme 3).

22 Scheme 3 Some of the reducing agents like stannous chloride, sulfur dioxide are used to reduce diorganoantimony(V) halides to diorganoantimony(III) halides.23 Dimeric structure of diphenylantimony trichloride: Michaelis and Reese first synthesized diphenylantimony trichloride where they obtained it as a monohydrate. When heating the monohydrated compound to 100 ?C they readily obtained the anhydrous compound. Initially there was uncertanity about the structure of Ph2SbCl3. Bordner et al resolved the ambiguity by examining the single-crystal X-ray diffraction data of the anhydrous Ph2SbCl3 and found that it exists as a dimer with chlorine bridges and geometry around antimony was found to be octahedral (Figure 3).24 Figure 3: Dimeric structure of diphenylantimony trichloride.

Bone and Sowerby synthesized diarylantimony(V) tribromide (Ph2SbBr3) and the two mixed halides Ph2SbBr2Cl and Ph2SbBrCl2.25 These compounds are monomeric in solid state and geometry around antimony was found to be trigonal-bipyramidal with two phenyl groups and a6 bromine atom occupying the equatorial positions. Due to weak intermolecular interactions arising between axial halogen atom and antimony, these units are linked to form infinite chains in solid state. On the other hand when compared with above mentioned compounds Ph2SbCl3 shows a dimeric nature in solid state. With various oxygen donor ligands such as DMSO and HMPA diorganoantimony(V) halides forms monomeric covalent adducts (R2SbX3.L).

Octahedral geometry has been proposed on the basis of IR and NMR spectra.26 Diorganoantimony ?-diketone derivatives: Diorganoantimony trihalide when treated with acetylacetone under reflux condition gave rise to diorganoantimony(V) ?-diketones, Ph2Sb(CH3COCHCOCH3)Cl2 (Scheme 4) which are monomeric in nature (Figure 4).27 Scheme 4 Figure 4: Diphenyldichloro(acetylacetonato)antimony & Dimethyldichloro(acetylacetonato)antimony. ?-diketonate ligand acts as bidentate ligand in both the complexes and the oxygen atoms from acetylacetone bonds to antimony atom. Interpretations drawn from 1H NMR spectral studies have been confirmed by single crystal X-ray diffraction analysis of Me2Sb(acac)Cl2 and Ph2Sb(acac)Cl2.28,29 Me2Sb(acac)Cl2 compound possess a slightly distorted octahedral geometry around antimony in which methyl groups occupy equatorial positions and are bent towards the planar acetylacetonato group. In compound Ph2Sb(acac)Cl2 the geometry around antimony was distorted octahedral in which the two chlorine are arranged trans to each other (Figure 4).

7 Schiff base derivative of diorganoantimony: Diorganoantimony(V) complexes with planar tridentate schiff base ligands (Trid) have been prepared by the exchange reactions of diorganoantimony(V) chlorides with corresponding schiff bases of trimethylantimony(V) or dimethyltin(IV) compounds (Scheme 5). These reactions proceed due to greater Lewis acidity of R2Sb(V) compared to Me3Sb(V) or Me2Sn(IV).30 Planar tridentate ligands (Trid) coordinate to antimony in ONO fashion, the chelating ONO atoms assumed to be arranged in a meridional fashion and a linear C-Sb-C skeleton has been proposed based on IR and 1H NMR studies.

Certain compounds such as Me2Sb(Sah)Cl, Me2Sb(Bah)Cl, Ph2Sb(Bah)Cl and Ph2Sb(Aah)Cl shows octahedral geometry with meridional arrangement as proven by Mossbauer spectroscopy (Figure 5).31 Scheme 5 Figure 5: Meridional arrangement of tridentate Schiff base ligand around antimony. Reaction with Silver salt of phosphinates: Diphenylantimony trichloride when treated with two equivalents of silver salts of phosphinates leads to the isolation of partially hydrolyzed product {SbPh2ClO2P(C6H11)2}2O (Scheme 6).7a Single crystal X-ray diffraction studies reveals that antimony atoms are in octahedral coordination with bridging phophinates cis to each other. The phosphinates in this compound only acts a bridging ligand. Scheme 68 Kumara Swamy and co-workers reported antimony(V) phosphinates by reacting diphenylantimony trichloride with three equivalence of silver acetate followed by one equivalence of phosphinic acid leading to the isolation of dimeric compounds of formula Ph2Sb(O2PR2)O2.

Interestingly when the dimer was reacted with acetic acid / water gives the tetra nuclear cage of formula Ph8Sb4O4(OH)2(O2P(C6H11)2)2 (Scheme 7).32 Scheme 7 Scheme 8 All the compounds are structurally characterized by single crystal X-ray diffraction analysis. In the di and the tetra nuclear clusters, the antimony atoms are octahedral coordinated with four membered Sb2O2 rings. In tetranuclear cluster two Sb2O2 rings are linked by oxo bridges on two sides to give a Sb4O6 cage (Scheme 8). Diorganoantimony based µ4-peroxo complex: The first main group element µ4-peroxo complex of antimony was synthesized by treating tetra-o-tolyldistibane in air and subsequent reaction with H2O2 and the intermediate (o-Tol2Sb4)O6 (Scheme 9) was identified by mass spectrometry.

The complex is stable in solution9 state. Single crystal X-ray diffraction studies reveal that antimony atoms are arranged as in the vertices of a square planar arrangement (Figure 6).33 Scheme 9 Figure 6: µ4-peroxo Complex of Antimony Synthesis of Quadruply bridged diorganoantimony compound: Quadruply bridged diorganoantimony compounds (SbPh2)2(µ-O)2(µ-O2AsR2)2,34 where R = Me or Ph have been synthesized by reacting (SbPh2BrO)2 with 2 moles of either Na(O2AsMe2) or Na(O2AsPh2) in DCM and the mixture was refluxed for 24 h. The compounds have been characterized by a various spectroscopic methods and analytical methods (Figure 7).

Figure 7: Quadruply bridged diorganoantimony compounds.10 Conclusion: This review describes the synthesis, spectroscopic and structure aspects of organ antimony compounds. References: (1) Krebs, R. E. The History and Use of our Earth’s Chemical Elements, Greenwood Press, Westport, Conn, 2004, 219. (2) Ulrich, N. Chem.

Eng. News, 2003, 81, 126. (3) (a) Singh, N. Indian J.

Med. Res. 2006, 123, 411. (b) Demicheli, C.

; Santos, L. S.; Ferreira, C. S.

; Bouchemal, N.; Hantz, E.; Eberlin, M. N.; Frezard, F.

Inorg. Chim. Acta 2006, 359, 159. (c) Brochu, C.; Wang, J.; Roy, G.

; Messier, N.; Wang, X.-Y.

; Saravia, N. C.; Ouellette, M. Antimicrob. Agents Chemother. 2003, 47, 3073.

(d) Rais, S.; Perianin, A.; Lenoir, M.; Sadak, A.

; Rivollet, D.; Paul, M.; Deniau, M. Antimicrob.

Agents Chemother. 2000, 44, 2406. (e) Ge, R.; Sun, H. Acc.

Chem. Res. 2007, 40, 267.

(4) (a) Jain, V. K.; Bohra, R.; Mehrotra, R. C. Struct. Bonding (Berlin) 1982, 52, 147.

(b) Gibbons, M. N.; Sowerby, D. B.

Phosphorus, Sulfur Silicon 1994, 93, 305. (c) Silvestru, C.; Silvestru, A.; Haiduc, I.; Sowerby, D.

B.; Ebert, K. H.; Breunig, H. J.

Polyhedron 1997, 16, 2643. (d) Garje, S. S.; Jain, V. K.

Main Group Met. Chem. 1999, 22, 45.

(e) Gupta, A.; Sharma, R. K.; Bohra, R.

; Jain, V. K.; Drake, J. E.

; Hursthouse, M. B.; Light, M. E. Polyhedron 2002, 21, 2387. (f) Yin, H. D.

; Zai, J. Inorg. Chim. Acta 2009, 362, 339.

(g) Quan, L.; Yin, H. D.; Cui, J. C.; Hong, M. J.

Organomet. Chem. 2009, 694, 3683.

(h) Yin, H. D.; Zai, J.; Sun, Y. Y.

Polyhedron 2008, 27, 663. (5) (a) Silvestru, C.; Silaghi-Dumitrescu, L.

; Haiduc, I.; Begley, M. J.

; Nunn, M.; Sowerby, D. B. J.

Chem. Soc., Dalton Trans. 1986, 1031. (b) Silvestru, C.; Curtui, M.

; Haiduc, I.; Begley, M. J.; Sowerby, D. B. J.

Organomet. Chem. 1992, 426, 49. (6) Silvestru, C.

; Socaciu, C.; Baba, A.; Haiduc, I. Anticancer Res. 1990, 10, 803. (7) (a) Said, M. A.

; Kumara Swamy, K. C.; Babu, K.; Aparna, K.; Nethaji, M.

J. Chem. Soc. Dalton Trans. 1995, 2151. (b) Dogamala, M.; Huber, F.

; Preut, H. Z. Anorg. Allg. Chem. 1989, 571, 130. (c) Li, J.

S.; Huang, G. Q.; Wei, Y.

T.; Xiong, C. H.; Zhu, D.

Q.; Xie, Q. L.

Appl. Organomet. Chem. 1998, 12, 31. (d) Ma, Y. Q.; Li, J.

S.; Xuan, Z. N.; Liu, R. C. J.

11 Organomet Chem. 2001, 620, 235. (e) Ma, Y.

Q.; Yu, L.; Li, J.

S. Heteroat. Chem. 2002, 13, 299. (f) Sharma, P.

; Perez, D.; Vazquez, J.; Toscano, A.; Gutierrez, R. Inorg. Chem.

Commun. 2007, 10, 389. (8) (a) Huang, Y. Z. Acc. Chem.

Res. 1992, 25, 182. (b) Cross, W. I.

; Godfrey, S. M.; McAuliffe, C.

A.; Mackie, A. G.; Pritchard, R. G.; Norman, N. C.

(Ed.), Chemistry of Arsenic, Antimony and Bismuth, Ch. 5, Blackie Academic and Professional, London, 1998. (9) WHO (World Health Organization), Leishmaniasis: disease information, 2007.

Available from: (10) Burrell, R. E.

; Corke, C. T.; Goel. R.

G. J. Agric.

Food Chem. 1983, 31, 85. (11) Socaciu, C.; Pasca, L.; Silvestru, C.

; Bara, A.; Haiduc. I. Metal-based drugs 1994, 1, 4. (12) Kohri, K.

; Yoshida, E.; Yasuike, S.; Fujie, T.

; Yamamoto, C.; Kaji. T. J. Toxicol. Sci.

2015, 40, 321. (13) (a) Kant, R.; Chandrashekar, A. K.; Anil. K. S.

Phosphorus, Sulfur and Silicon 2008, 183, 1410. (b) Kant, R.; K. Singhal, K.

; Shukla, S. K.; Chandrashekar, K.; Saxena, A. K.; Ranjan, A.; Raj.

P. Phosphorus, Sulfur and Silicon. 2008, 183, 2029. (14) Agrawaly, R.

; Sharmay, J.; Nandaniz, D.; Batraz, A.; Singh. Y. J.

Coord. Chem. 2011, 64, 554. (15) Barsukova-Stuckart, M.; Piedra-Garza, L.

F.; Gautam, B.; Alfaro-Espinoza, G.

; Izarova, N. V.; Banerjee, A.; Bassil, B. S.; Ullrich, M.

S.; Breunig, H. J.; Silvestru, C.

; Kortz, U. Inorg. Chem. 2012, 51, 12015. (16) (a) Seiple, L.A.; Cardellina, J.

H.; Akee, R.; Stivers, J. T. Mol. Pharmacol.

2008, 73, 669. (b) Kim, H.; Cardellina, J. H.; Akee, R.

; James J. Champoux, J. J.; and Stivers, J. T. Bioorg. Chem.

2008, 36, 190. (c) Rishi, V.; Oh, W.-J.; Heyerdahl, S.

L.; Zhao, J.; Scudiero, D.

; Shoemaker, R. H.; Vinson, C. J. Struct.

Biol. 2010, 170, 216. (d) Heyerdahl, S. L.; Rozenberg, J.; Jamtgaard.; Rishi, V.

; Varticovskik, L.; Akah, K.; Scudiero, D.; Shoemaker, R.

H.; Karpova, T. S.; Day, R.

N.; McNally, J. G.; Vinson.

C. Eur. J. Cell Biol. 2010, 89,12 564. (e) Zhao, J.

; Jason, R.; Stagno, J. R.; Varticovski, L.; Nimako, E.; Rishi, V.; McKinnon, K.

; Akee, R.; Shoemaker, R. H.; Ji, X.; Vinson. C. Mol.

Pharmacol. 2012, 82, 814. (17) (a) Schmidt, H.; Justus Liebigs Ann. Chem. 1920, 421, 174. (b) Worrall, D.

E. J. Am. Chem. Soc.

1930, 52, 2046. (c) Biswell, C. B.; Hamilton, C. S. ibid. 1935, 57, 913.

(c) Morgan, G. T.; Davies, G. R. Proc.

Roy. Sec. (London), Ser.

A, 1926, 110, 523. (18) Nishii, N.; Hashimoto, K.; Okawara, R. J.

Organomet. Chem. 1973, 55, 133.

(19) (a) Kawasaki, Y.; Okawara, R. Bull. Chem. Soc.

Japan 1967, 40, 428. (b) Meinema, H. A.; Noltes, J. G. J. Organometal.

Chem. 1969, 16, 257. (c) Meinema, H. A.; Mackor, A.; Noltes, J. G.

J. Organometal. Chem. 1972, 37, 285.

(d) Nishii, N. Inorg. Nucl. Chem. Lett. 1969, 5, 529.

(20) (a) Kanehisa, N.; Kai, Y.; Kasai, N. Inorg.

Nucl. Chem. Lett. 1972, 8, 375. (b) Kanehisa, N.

Bull. Chem. Soc. Japan 1978, 51, 2222. (21) (a) Breunig, H. J.; R?sler, R.

; Lork. E. Organometallics 1998, 17, 5594. (b) Piedra-Garza, L. F.; Dickman, H. M.

; Moldovan, O.; Breunig, H. J.; Kortz.

U. Inorg. Chem. 2009, 48, 411. (22) (a) Bamgboye, T. T.

; Begley, M. J.; Sowerby, D. B.

J. Organomet. Chem. 1989, 362, 77. (b) Rahman, F. M.

M.; Murafuji, T.; Ishibashi, M.; Miyoshi, Y.; Sugihara, Y.

J. Organomet. Chem. 2004, 689, 3395. (c) Bone, S. P.

; Sowerby, D. B. J. Chem. Soc. Dalton Trans.

1979, 715. (23) (a) Campbell, I. G. M. J.

Chem. Soc. 1952, 4448. (b) Campbell, I. G. M.

; Morrill, D. J. J. Chem. Soc. 1955, 1662.

(24) (a) Michaelis, A.; Reese, A. Justus Liebigs Ann. Chem. 1886, 39, 233.

(b) Polynova, T. N.; Porai-Koshits, M. A.

Zh. Strukt. Khim. 1961, 2, 477. (c) Polynova, T. N.; Porai-Koshits, M.

A. Zh. Strukt.

Khim. 1966, 7, 642. (d) Ruddick, J. N. R.

; Sams, J. R.; Scott, J. C. Inorg.

Chem. 1974, 13, 1503. (e) Bordner, J.; Doak, G.

O.; Peters, Jr. J.

R. J. Am. Chem.

Soc. 1974, 96, 6763.13 (25) (a) Bone, S. P.; Sowerby, D. B. J.

Chem. Soc. Dalton Trans. 1979, 715.

(b) Bone, S. P.; Sowerby, D. B. ibid. 1979, 718. (26) (a) Nishii, N.

; Matsumura, Y.; Okawara, R. ibid. 1971, 30, 59.

(b) Popov, V. I.; Kondratenko, N. V. Zh.

Obsh. Khim. 1976, 46, 2579; C. A. 86, 121457.

(27) Meinema, H. A.; Noltes, J. G.

J. Organometal. Chem. 1969, 16, 257.

(28) Kanehisa, N. Bull. Chem.

Soc. Japan 1978, 51, 2222. (29) Uda, S. Cryst. Struct. Commun. 1974, 3, 257.

(30) (a) Di Bianca, F. Atti. Accad. Sci.

Lett. Arti. Palermo, Part 1 1973, 33, 173; C. A. 83, 114572. (b) Meinema, H. A.

J. Organometal. Chem. 1976, 107, 249.

(31) Bertazzi, N. J .Chem. Soc. Dalton Trans. 1977, 957. (32) Said, M. A.; Kumara Swamy, K. C.; Poojary, D. M.; Clearfield, A.; Veith, M.; Huch, V. Inorg. Chem. 1996, 35, 3235. (33) Breunig, H. J.; Kruger, T.; Lork. E. Angew. Chem. Int. Ed. Engl. 1997, 36, 615. (34) Sowerby. D. B. J. Chem. Soc., Dalton Trans. 1997, 2785.