Transcript Presentation - Harlem Children Society

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:
Tissue/wound repair
Resistance to
infection
Natural growth
Manufacture &
regulation of genetic
material
•
•
•
•
•
Antioxidant enzymes
Energy production
Healthy immune &
reproductive systems
Hormone production
and use in the body
Antiviral properties
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 fivesided ‘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
• Added glycine gradually
increases the solubility of
[ZnO]0.47[Zn(citr)]0.53
• Increase in percent
solubility from 3-4 molar
excess may be due to
experimental error in
preparation of salt
% Zinc Titrated
~22% in gylcine.
Zinc Titrated with Glycine
90
80
70
60
50
40
30
20
10
0
y = -0.0697x2 + 3.6929x + 31.893
R2 = 0.839
0
5
10
15
20
Rel. Mol. Glycine
• Maximum solubility of 79% was
seen at a glycine to total zinc molar
ratio of 20:1
25
Zinc Citraconate and Alanine
Zinc Titrated with Alanine
• Added alanine gradually
80
increases the solubility of
70
[ZnO]0.47[Zn(citr)]0.53
y = -0.0573x + 2.1244x + 66.548
60
R = 0.5127
• Maximum solubility of
81% was seen at a alanine 50
0
5
10
15
20
25
30
35
Rel.
Mol.
Alanine
to mixed zinc salt molar
• Alanine is less polar than glycine, and
ratio of 20:1
• 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)
% Zn Titrated
90
2
2
Zinc Citraconate and Serine
100
% Zinc Tritrated
• Added serine increases
the solubility of the
mixed zinc salt
[ZnO]0.47[Zn(citr)]0.53
• Maximum solubility of
72% was seen at a
serine to total zinc molar
ratio of 1:1
Zinc Titrated with Serine
80
60
40
y = -0.0827x + 72.161
R2 = 0.9512
20
0
0
2
4
6
8
10
Rel. Mol. Serine
• Lack of significant change in
solubilities indicates a need to
repeat experiment with better
prepared zinc citraconate
12
Modeling the Zinc
Citraconate:Glycine System
Speciation Diagram of Citraconic Acid
Glycine Speciation as a function of pH
1.2
1
1
0.8
alpha
α
0.8
0.6
0.4
0.6
0.4
0.2
0.2
0
1
2
3
4
5
pH
6
7
8
0
0
1
2
3
4
5
6
7
8
9
10
11
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-
12
13
14
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
• Bobtelsky, M.; Jordan, J. J. Am. Chem. Soc. 1945, 67, 1824-31.
• Campi, E.; Ostacoli, G. et al. J. Inorg. Nucl. Chem. 1964, 26, 55364.
• 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.
• Cunningham, J.J.; Lydon, M.K.; et al. J. Am. Coll. Nutr. 1991, 10,
57-62.
• Haertl, E. J. Agric. Food Chem. 1963, 11, 108-11.
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.