The Effect of Amino Acids on

the Solubility of Zinc

Citraconate

Rhomesia Ramkellowan
Mentor: Sabrina G. Sobel
Hofstra University
 Abstract
• Zinc salts are known to shorten the duration and
severity of the common cold.
• Increasing the percentage of free zinc ions as
compared to chelated zinc increases the efficacy of
this treatment.
• A study of the influence that amino acids have on the
solubility of zinc citraconate may be relevant to such
zinc ion therapy.
• It is hoped that this research may help aid future
development of medical zinc salt treatments.
 Introduction
• Zinc complexes are important in biological and industrial contexts
• Treatment of common cold (treatment within 24 hrs: 4.8
days ill vs. 9.2 days ill)
• Wound healing (promotes debridement and healing of burn
wounds)
• Plant nutrition (provides an essential nutrient)
• Removal of zinc from coal fly ash (reduce environmental
zinc overload = pollution)
• What form of zinc is best for each situation?
• Are free zinc ions (weakly complexed) or strongly
complexed zinc ions more beneficial?
• Strong complexes for the removal of zinc; weak complexes
for the delivery of zinc
 Zinc and the Body
• Zinc is essential for: • Antioxidant enzymes
• Tissue/wound repair • Energy production
• Resistance to • Healthy immune &
infection reproductive systems
• Natural growth • Hormone production
• Manufacture & and use in the body
regulation of genetic • Antiviral properties
material
 Zinc Ion Therapy

• For treating the common cold

• For treating minor burns, cuts,
scrapes, abrasions and infections
• For treating mouth canker sores
• For treating bad breath
• For treating shingles
Attack of the Cold Virus
• Cold virus binds to positive
projections on cell surface
• Cold virus uses its
negatively charged five-
sided ‘canyons’
• 1/5th of a canyon can be
used for zinc binding model
• Related viruses: herpes,
chicken pox
Model of Zinc Binding to
Cold Virus
• Six binding sites found
• Total Zn2+ ions needed for each
virus: 360
• Comparison of viral loading to
lozenge therapy:
23 mg Zn2+ from lozenge in 25 mL
saliva = 13.1 mM
1% transfer to nose = 0.131 mM
typical viral load = 108 virions/L
excess Zn2+= 8 x 1011 Zn2+/virion
 Procedure
• Zinc citraconate was combined with varying molar
amounts of amino acids
• Glycine, alanine and serine
• Each solution was titrated with Na2EDTA
• To determine the total zinc ion content in the
solutions
• To find the percent of zinc citraconate that dissolved
and the percent zinc titrated
Organic Molecules Used

Alanine

Citraconic acid

Serine

Glycine
 Zinc Citraconate and Glycine
• Zinc titrated starts at Zinc Titrated with Glycine
90
~22% in gylcine. 80

% Zinc Titrated
70
• Added glycine gradually 60
50

increases the solubility of 40

30 y = -0.0697x2 + 3.6929x + 31.893
20
[ZnO]0.47[Zn(citr)]0.53 10
R2 = 0.839
0
• Increase in percent 0 5 10 15 20 25

Rel. Mol. Glycine

solubility from 3-4 molar
excess may be due to
experimental error in • Maximum solubility of 79% was
preparation of salt seen at a glycine to total zinc molar
ratio of 20:1
 Zinc Citraconate and Alanine
Zinc Titrated with Alanine
• Added alanine gradually 90

% Zn Titrated
80
increases the solubility of
[ZnO]0.47[Zn(citr)]0.53 70
2
y = -0.0573x + 2.1244x + 66.548
• Maximum solubility of 60 R = 0.5127
2

81% was seen at a alanine 50

0 5 10 15 20 25 30 35
to mixed zinc salt molar Rel. Mol. Alanine

ratio of 20:1 • Alanine is less polar than glycine, and

• Composite Ksp of mixed serine is more polar that glycine
salt is 1.47 x 10-4 • Order in solubilites is not clear –
possibly due to impure starting material
(mixed zinc salt instead of zinc
citraconate)
 Zinc Citraconate and Serine
Zinc Titrated with Serine
• Added serine increases 100
the solubility of the

% Zinc Tritrated
80
mixed zinc salt 60

[ZnO]0.47[Zn(citr)]0.53 40 y = -0.0827x + 72.161

• Maximum solubility of 20 R2 = 0.9512
0
72% was seen at a 0 2 4 6 8 10 12
serine to total zinc molar Rel. Mol. Serine

ratio of 1:1
• Lack of significant change in
solubilities indicates a need to
repeat experiment with better
prepared zinc citraconate
 Modeling the Zinc
Citraconate:Glycine System
Speciation Diagram of Citraconic Acid Glycine Speciation as a function of pH
1.2
1
1
0.8
0.8
0.6

alpha
α 0.6
0.4
0.4
0.2
0.2
0
0
1 2 3 4 5 6 7 8
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14
pH pH

• Standard plots of acid speciation as a function of pH based on

acid ionization constants. Citraconic acid:blue = H2citr, red =
Hcitr-, green = citr-2; Glycine: green = Hgly+, blue = gly
zwitterion, red = gly-
Total Metal Ion and Ligand
Concentrations
•These equations provide a way
to test if mixed ligand complexes
are important.
• If TM = calculated values from
all measured concentrations, then
mixed ligand complexes are not
important.
• The same analysis can be
completed with ligand.
• Determination of free [Zn] via
ion specific electrode titration is
essential to this analysis.
 Conclusion
• Attempted synthesis of zinc citraconate was partially successful
• It was concluded that while making zinc citraconate, a mixed zinc salt
was made
• Elemental analysis showed 46.4% Zn in the salt prepared, which is
consistent with a mixed salt: [ZnO]0.47[Zn(citr)]0.53 (Theor: 46.44%,
Exptl 46.4%)
• Zinc titrated did show general trends seen in group previously
• Percent zinc dissolved increased as amino acid ratio increased
• Added amino acid dramatically enhances solubility of mixed zinc salt
prepared
• Enhancement of solubility cannot solely be due to protonation
of salt anion by free amino acid as pK’s of anions and amino
acids are comparable
 Future Work
• Create new method to synthesize pure zinc citraconate
• Analysis of salt will be done before titrations with
amino acids
• Expect percent zinc dissolved to increase as amino
acid ratio increase
• Expect to see an increase in free [Zn2+] as the amino
acid : zinc salt ratio increases
 Bibliography
Analytical Articles
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• Campi, E.; Ostacoli, G. et al. J. Inorg. Nucl. Chem. 1964, 26, 553-
64.
• Childs, C.W.; Perrin, D.D. J. Chem. Soc. A 1969, 1039 - 44.
• Novick, S.G. J. Chem. Educ. 1997, 74, 1463.
• Zarembo, J.E.; Godfrey, J.C.; Godfrey, N.J. J. Pharm. Sci. 1992, 81,
128-30.
Medical/Agricultural Articles
• Novick, S.G.; Godfrey, J.C. et al. Med. Hypoth. 1996, 46, 295-302.
• Henzel, J.; DeWase, M. et al. Arch. Surg. 1970, 100, 349.
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 Acknowledgments
• Tracy Concepcion, Allison Haigney: additional
mentors,
• Lois and Mike: helpful co-researchers,
• Hofstra U. Chemistry Department: site sponsor,.
Partially funded by Godfrey Science & Design, Inc.,
Huntingdon Valley, PA
• Ms. Susan Fahrenholtz, Project Seed and the
American Chemical Society,
• Dr. Sat Bhattacharya and Harlem Children Society.