Abstract:
In a quest to discover new formulations for the treatment of various parasitic diseases, a
series of triorganobismuth(v) biscarboxylates of type [R3Bi(O2CR′)2] have been synthesized,
characterized and evaluated for their biological potential. The organic moiety R in the
organometallics represents Ph for (1-10) and CH3-Ph for (11-22) whereas R′ represent the
respective carboxylate ligands used. All the synthesized complexes were fully characterized
by elemental analysis, FT-IR, multinuclear (1H, 13C) NMR spectroscopy and single crystal Xray
analysis. The crystal structures for (1-6, 8, 10, 18) have been ascertained and confirmed
distorted trigonal bipyramidal geometry, being monomeric with seven/five coordinated
bismuth center as predicted by IR data. The synthesized complexes (1-21) when screened for
antibacterial, antifungal and antileishmanial activity, demonstrated a moderate to significant
potential against these microorganisms. Enzyme inhibition data for these complexes also
proved to be convincing enough to signify the biological importance of these compounds. A
limited Structure Activity Relationship (SAR) has been developed, demonstrating that
triphenylbismuth derivatives exhibit higher biological activities in general as compared to
tritolyl bismuth derivatives.
Two new bismuth-oxido Carboxylate clusters (23, 24) have been synthesized
including the outcome of a structurally unprecedented Bi12 Carboxylate cluster that is the first
of its own kind. Both these were fully characterized by elemental analysis, FT-IR,
multinuclear(1H, 13C) NMR spectroscopy and X-ray crystallography.
The triphenylbismuth(III) and trifluoroacetic acid (TFAH) were reacted in toluene in
the presence of Ag2O to generate the hetronuclear compound with formulation as; {[Bi4(μ3-
O)2(TFA)9Ag(tol)2]2} (25) (tol = PhMe). Similarly, BiPh3, TFAH, PPh3, and Ag2O were
reacted in hexane to form [Bi4(μ3-O)2(TFA)10(AgPPh3)2]n (26). Both are comprised of
{Bi4(μ3-O)2} units that have been previously observed with a variety of carboxylate ligands
in neutral compounds and anionic compounds. In contrast to other anionic [Bi4(μ3-
O)2(TFA)N](N-8)- with metal-based counter cations, the Ag+ ions in (25) and (26) are directly
attached to oxygen atoms of the TFA- ligands bonded to the bismuth core. A crystallographic
evolution was observed for (25). Solvent-rich orthorhombic crystals grew initially upon
standing. However, by three weeks all crystals had converted to a triclinic unit cell that
contained no free solvent. Therefore molecular volume decreased from 3146.11 Å3
(orthorhombic) to 2954.06 Å3 (triclinic) resulting in formation of (25). The latter (25)
possessed an intermolecular π- π stacking system between silver- and bismuth-bound toluene
molecules, which explains the reorganization to a non-solvated morphology. The compound
(26) crystallizes in the triclinic space group P-1 as a coordination polymer through bridging
xiv
carboxylates. The presence of the PPh3 ligands on Ag+ results in a higher Ag:Bi
stoichiometry than for (25). The importance of the Ag2O in generating the oxido ligands was
confirmed by the isolation of {[Bi2(TFA)6(TFAH)(tol)]2}n (27) from the reaction of BiPh3
with TFAH in toluene in absence of the metal oxide. A unique and previously unknown
hexanitratobismuth(III) anion, [Bi(NO3)6]3− is reported for 28;
[Co{HC(MeCO)2(MeCNH)}2][Bi(NO3)6].
To further explore the potential application of another main group metal, germanium,
a series of substituted dihydropyrimidin-2(1H)-thione derivatives (29-36) have been
synthesized using a facile and modified procedure with triphenylgermyl propionate as a
catalyst. In comparison with the classical Biginelli reaction, this new protocol has the
advantages of excellent yield and shorter reaction times. The synthesized compounds have
been characterized by various spectroscopic techniques such as FT-IR, multinuclear (1H/13C)
NMR spectroscopy and single crystal XRD analysis. Molecular docking studies were
performed to identify the probable binding modes of potent inhibitors in the active site of the
enzymes human topoisomerase II alpha (4FM9) and Helicobacter pylori urease (1E9Y). The
compound (31) was evaluated to be the most potent inhibitor according to the molecular
docking scores and molecular dynamic simulations which suggest it can be further processed
as a lead molecule to interpret the pharmacological properties of such type of compounds.