PROJECT NO.

#08
Synthesis of Transition Metals (Co -II, Fe- II,
Ni- II, Mn- II, Cu- II) Complexes with 4-
Aminobenzoic Acid.
Submitted by: Group 04
Submitted to: Dr. Muhammad Tariq
Semester: BS 8th

Institute of Chemical Sciences, BZU,

MULTAN.

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Synthesis of Transition Metals (Co -II, Fe- II, Ni-
II, Mn- II, Cu- II) Complexes with 4-
Aminobenzoic Acid.
Abstract
Para-aminobenzoic acid is an organic compound with the formula C7H7NO2. It is a
naturally-occurring, organic, unsaturated 4-Aminobenzoic Acid. It is an intermediate in the
synthesis of folate by bacteria, plants, and fungi. Many bacteria, including those found in the
human intestinal tract such as E. coli, generate Para-aminobenzoic acid from chorismate by the
combined action of the enzymes 4-amino-4-deoxychorismate synthase and 4-amino-4-
deoxychorismate lyase. Plants produce Para-aminobenzoic acid in their chloroplasts, and store it
as a glucose ester (pABA-Glc) in their tissues. This piece of paper investigates the synthesis of
transition metal complexes of 4-Aminobenzoic Acid with five transition metals namely cobalt,
iron, nickel, manganese and copper. The five transition metal complexes [M(PABA)n. nH2O]
(M=Co -II, Fe- II, Ni- II, Mn- II, Cu- II) were prepared by the reaction of 4-Aminobenzoic Acid
(sodium salt) with respective metal salt solution. Synthesis consists of two steps, in first step 4-
Aminobenzoic Acid is treated with sodium hydroxide to give an intermediate specie; sodium 4-
Aminobenzoate which furthers reacts with metal salts to give metal complexes with 4-
Aminobenzoic Acid. The percentage yield of the complexes formed was found. The proposed
geometry of all prepared [M(PABA)2. nH2O] is tetrahedral.

Introduction
A 4-Aminobenzoic acid or simply PABA is an isomeric form of aminobenzoic acid, which
consists of a carboxylic and amine functional group. PABA can exist in three forms (neutral, anion,
and cation) according to the pH of the environment. PABA often found and as ligand bind to a
metal ion. PABA has been applied to medical interest in the past decade, particularly related to its
effects on microorganism metabolism. It has been reported that PABA has antibacterial activity
against E. coli at lower pH. The inhibitory effect on bacterial growth is known related to the
carboxylic functional group. Inhibition of bacterial enzymes is one common mechanism to induce
the antibacterial activity of antibacterial compounds in drugs. Incorporating PABA into whey
protein-based film led to inhibition of L. monocytogenes, E. coli, and S. Typhimuriumat pH 5.2.
The interactions of PABA in that edible film resulted in different diffusion rates leading to
varying degrees of inhibition. PABA can enhance the antibacterial activity of antibiotics and other
primary antibacterials in both topical and systemic use against P. aeruginosa, E. cloacae, and S.
aureus by sub inhibit concentration combination which resulted in the synergistic effect. It is
identified that PABA is a good candidate for imaging a broad range of bacterial infections. A radio-
fluorinated analog of PABA has been developed for a rapid and noninvasive diagnostic tool to
detect and locate S. aureus infection and guide antimicrobial selection. PABA derivatives were
reported for their potential inhibitory property against novel antibacterial targets.

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Thiosemicarbazones of PABA were synthesized and the hydroxamatederivates found to have good
antimicrobial activity against E. coli, K. pneumoniae, S. aureus, V. cholerae, and B. subtilis.
The development of antimicrobial agents through structure design and modification is
important to overcome widespread bacterial and fungal infection cases. The various synthetic
methods mostly used to connect two or more active derivative compounds into the new structures
to improve activity compared to the initial compounds. Synthesis and characterization of the metal-
para-aminobenzoic acid complex have been studied as they possess antimicrobial activity against
pathogenic microorganisms. The widespread use of metal transition complex as an antimicrobial
in medicine has been developed for many years. The complexation of metal ions and ligands
increases their biopotential activity compared to their simple form as the changes in their shape,
size, charge density distribution, and/or redox potential. These complexes consist of an array of
ligand that has available electrons for donating towards positively charged metal ions, forming
covalent bonds.
The complex properties are associated with the nature and structure of the complexes. The
mechanisms of action against the microorganism can be different depending on the complex, i.e.
by occupy surface sites, penetrate the cell wall, and disturb different molecule targets. The different
examples of selected metals with antimicrobial activity applications have been reported, including
Cu(II), Zn(II), and Fe(II) complexes. The studies were performed to compare the antimicrobial
activity of complexes with a specific ligand and different metal ions or vice versa as the nature of
different metal ions and the donor sequence of the different ligands reveal can affect the biological
activity of the compounds.
Some Metal(II)-PABA derivatives complexes were synthesized and tested for
antimicrobial activity against Staphylococcus sp., Escherichia spp., and Streptococcus spp. The
result showed that Mn(II), Fe(II), and Zn(II) complexes of dimethyldithiocarbamic and PABA had
very good antimicrobial activity against these microbes which proving their potentials as broad-
spectrum antimicrobial agents in-vitro. Metal(II) complexes derived from β-diketoneand PABA
were synthesized and characterized include infrared (IR) and electronic spectra measurement.
Furthermore, the study result showed that Mn(II) and Fe(II) complexes have good reactivity that
might be significant in the development of drugs against pathogenic microorganisms. Synthesis of
Cu(II)-PABA complex had been performed and it was tested for antimicrobial activity by diffusion
techniques. The result showed the complexation of PABA with Cu(II) has significant antimicrobial
activity against E. faecalis, S. aureus, B. subtilis, and L. monocytogenes compared to PABA
ligand.
Iron is an essential transition metal ion that can coordinate with organic molecules
presentingantimicrobialactivity. This ion is possible to be used as an active drug carrier in the cell.
Iron(II) participate in the Fenton reaction, which reacts with H2O2 to form reactive hydroxyl radical
that can damage proteins and nuclear acids. Iron is an important element in the establishment of a
pro-oxidant condition in the cell which led to cellular DNA damage. The microorganism’s growth
will be inhibited under the excessive concentration of iron. This exploration of the antibacterial
mechanism of iron against bacteria becoming one of the bases used of Iron(II) complexes as
antibacterial agents.i

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 In this study transition metal complexes of transition metals (Co -II, Fe- III, Ni- II, Mn- II,
Cu- II) were prepared with 4-Aminobenzoic Acid which act as chelating agent due to couple of
donor sites present on it. Synthesis of these complexes consists of two steps. In first step, 4-
Aminobenzoic Acid reacts with sodium hydroxide to give intermediate salt of sodium 4-
Aminobenzoate which further reacts with transition metal salt to give the complex of desired
transition metal with 4-Aminobenzoic Acid.

Experimental Work
[Co(4-Aminobenzoate)2] Complex
Solutions of NaOH (0.15g,3.64mmol in 20ml water), 4-Aminobenzoic Acid
(0.5g,3.64mmol in 20ml) and both these solutions were mixed to make sodium 4-Aminobenzoate
solution. Solution of (0.53g,1.82mmol dissolved in 20ml water) Co(NO3)2.6H2O was also
prepared. Solution of sodium 4-Aminobenzoate and metal salt solution were mixed. Stirring was
done until the precipitates of the complex were formed. In end, these precipitates were filtered.
Co(NO3)2.6H2O + 2 C7H6NO2Na Co(C7H6NO2)2 + 2NaNO3 + 6H2O
Cobalt 4-Aminobenzoate

[Fe(4-Aminobenzoate)2] Complex
Solutions of NaOH (0.15g,3.64mmol in 20ml water), 4-Aminobenzoic Acid (0.50gmmol
in 20ml) and both these solutions were mixed to make sodium 4-Aminobenzoate solution. Solution
of (0.50g,1.80mmol dissolved in 20ml water) FeSO47H2O was also prepared. Solution of sodium
4-Aminobenzoate and metal salt solution were mixed. Stirring was done until the precipitates of
the complex were formed. In end, these precipitates were filtered.
FeSO4.7H2O + 2C7H6NO2Na Fe(C7H6NO2)2 + Na2SO4 + 7H2O
Iron 4-Aminobenzoate

[Mn(4-Aminobenzoate)2] Complex
Solutions of NaOH (0.15g,3.64mmol in 20ml water), 4-Aminobenzoic Acid
(0.5g,3.64mmol in 20ml) and both these solutions were mixed to make sodium 4-Aminobenzoate
solution. Solution of (0.30g,1.77mmol dissolved in 20ml water) MnSO4.H2O was also prepared.
Solution of sodium 4-Aminobenzoate and metal salt solution were mixed. Stirring was done until
the precipitates of the complex were formed. In end, these precipitates were filtered.
MnSO4.H2O +2 C7H6NO2Na Mn(C7H6NO2)3 + Na2SO4 + H2O
Manganese 4-Aminobenzoate

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[Ni(4-Aminobenzoate)2] Complex
Solutions of NaOH (0.15g,3.64mmol in 20ml water), 4-Aminobenzoic Acid
(0.5g,3.64mmol in 20ml) and both these solutions were mixed to make sodium 4-Aminobenzoate
solution. Solution of (0.36g,1.80mmol dissolved in 20ml water) NiCl2.4H2O was also prepared.
Solution of sodium 4-Aminobenzoate and metal salt solution were mixed. Stirring was done until
the precipitates of the complex were formed. In end, these precipitates were filtered.
Ni(NO3)2.4H2O + 2 C7H6NO2Na Ni(C7H6NO2)2 + 2NaCl + 4H2O
Nickle 4-Aminobenzoate

[Cu(anthranilate)2] Complex
Solutions of NaOH (0.15g,3.64mmol in 20ml water), 4-Aminobenzoic Acid
(0.5g,3.64mmol in 20ml) and both these solutions were mixed to make sodium 4-Aminobenzoate
solution. Solution of (0.44g,1.82mmol dissolved in 20ml water) CuSO4.5H2O was also prepared.
Solution of sodium 4-Aminobenzoate and metal salt solution were mixed. Stirring was done until
the precipitates of the complex were formed. In end, these precipitates were filtered.
CuSO4.5H2O + 2 C7H6NO2Na Cu(C7H6NO2)2 + 2Na2SO4 + 5H2O
Copper 4-Aminobenzoate

Results and Discussion

Transition metal complexes of transition metals (Co -II, Fe- III, Mn- II, Ni- II, Cu- II) were
successfully prepared with 4-Aminobenzoic Acid. All complexes formed are stable in air and show
specific colours.
4-Aminobenzoic Acid has two electron donor sites as oxygen atom of the carboxylic group
and nitrogen atom of amino group contribute in the formation of two coordination bonds with any
transition metal. Basically, one oxygen of the carboxylic group with a negative charge donates two
electrons to the metal and the other nitrogen atom of the amino group donates it lone pair of
electrons to the metal for the sake of coordination bond. Transition metals like Co -II, Fe- II, Mn-
II, Ni- II, Cu- II form complexes with two molecules of 4-Aminobenzoic Acid as these metals
exists in +2 oxidation state and give sp3 hybridization to make tetrahedral geometry.
Proposed structuresii of complexes of these transition metals are illustrated below in
figures:

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 [Cu(PABA)2] Complex [Co((PABA)2] Complex
Hybridization state: sp3 sp3
Geometry: Tetrahedral Tetrahedral
% Yield: 82% 59%

[Mn(PABA)2] Complex [Ni(PABA)2] Complex

Hybridization state: sp3 sp3
Geometry: Tetrahedral Tetrahedral
% Yield: 78% 82%

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 [Fe(PABA)2] Complex
Hybridization state: sp3
Geometry: Tetrahedral
% Yield: 73%

References
i
Synthesis and Characterization of Iron(II)-4-aminobenzoic acid complex as Potent Antibacterial agent
Anisya Lisdiana1,2*, HerkuswynaIsnaniyah Wahab1,Sentot Budi Rahardjo2, Teguh Endah Saraswati2
ii
Synthesis and Characterization of Iron(II)-4-aminobenzoic acid complex as Potent Antibacterial agent
Anisya Lisdiana1,2*, HerkuswynaIsnaniyah Wahab1,Sentot Budi Rahardjo2, Teguh Endah Saraswati2

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