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γ-Cyclodextrin mediated supramolecular control of photochemical reactions
By Nga Nguyen-Undergraduate
Research Advisor: Mahesh Pattabiraman, Ph.D
Department of Chemistry
University of Nebraska-Kearney
Photodimerization• Photodimerization is a cycloaddition reaction involving two π bonds of two
neighboring molecules.
AB
AB
*A
B
*
AB
*
A
B*
A
B
AB
*
AA
A
A B
B A
B A
B
(hυ)
• Controlling the orientation of olefins and directing them to any stereospecific cyclobutane creates diverse products.
H
tH
t
H
tH
tH
tt
H
H
tt
H
H
t
H
t
H
t
H
tH
t
t
H
H
t
t
H
Natural products with cyclobutane core have medicinal values
O
O
O
O
NH
H
N
H
H
N
N
O
OH
O
OH
AntinociceptivePulmonary hypertension treatment
O
N
N
O
OO
OO
O O
Neuroprotector
Method
Using solution phase which is convenient and suitable for achieving higher conversion as a method instead of solid state that have been reported less general, requiring considerable preparation and are often limited by poor conversions and low yields.
Among many methods available to pre-orient molecules in solution phase, supramolecular control using host-guest chemistry of cavitand is shown convenient and effective strategy.
Photo-polymerization
• The complexes are useful in synthesis polymer that has wide applications in science materials.
Ma, and Tian Acc. Chem. Res. 2014
γ-Cyclodextrin(γ-CD)
γ-CD composed by 8 sugar molecules connecting together γ-CD has cone shape structure with the hydrophilic outside
and hydrophobic inside and function as a macromolecular host for photo-heterodimerizarion.
γ-CD is readily available, environmental and low cost
O
OHHO
OH
O
O
OH
HOOHO
OOH
OH
OH
O
O
OH
OH
OH
O
O
OH
OH
HO
O OH
OH
HO
O
OOH
HO
HO
O
O
OH
OH
HO
O
O
H
7.5 Å
8.3 Å
7.9 Å
Why γ-Cyclodextrin?
• The ability of γ-Cyclodextrin to encapsulate two alkenes simultaneously to form 1:2 inclusion complexes has been employed but the photo-heterodimerization within γ-CD has not been demonstrated.
• γ-CD has been well studied for their role as solubilizing and confining agents to steer excited state reactivity towards regioselective and stereoselective outcomes.
Hypothesis
Any specific alkenes that have steric complementarity and electronic complementarity can form the inclusion within the γ-Cyclodextrin cavity in which the 1:1:1 hetero-complex is dominant.
Purpose of research is to find how changes in properties of alkenes effects the formation of complex that depend upon steric and electronic complementary.
Cinnamic acid and coumarin pair The reaction between cinnamic acid and coumarin pair with in g-CD
cavity yield following possible outcomes. Reaction occurred with 42% heterodimer and 49% homodimer.
OH
O
O Oh
OHO
R
HOOC COOH
HOOC COOH
COOH
HOOC
COOH
HOOC
h
O OO O
O OO O
O
OO
O
O
OO
OHOOC HOOC
HOOC
O
O O
O
HOOC
O
O
h
h
Reasoning for the formations
Possible weak electronic interactions such as pi-pi, hydrogen bond responsible for inside interaction between host γ-CD and guest molecules.
When the size of guests molecules is compatible and confined to the limited cavity volume of γ-CD , the result is “right fix” inclusion complex. Two larges guest molecules are unable to fit.
Steric complementarity
Electronic complementarity
Procedures
Irradiation
The white precipitate was filtered, washed with water and organic solvents.
Products are irradiated between glass plates using medium pressure mercury vapor lamp.
Complexation.
Biphasic extraction
Analysis
What happen if 6-methyl coumarin (6MeCU) is used?
• 6-methyl coumarin with a bulky group compared to unsubstituted cinamic acid Test steric complementarity.
• As both alkenes are photoactive, a total of twelve homo-and heterodimers are possible.
• Heterodimers are deduced to better understand the reaction outcomes four possible 6-MeCU heterodimers within g-CD.
Head-HeadHead-TailTail-TailTail-Head
O OOH
Oh
-CD?
Head Tail TailHead
Heterodimer outcomes
OH
O
OH
O
O O
H
H
H
O O
H
H
H
OO
H
H
H
OH
O
OH
O
O O
H
H
HOH
OOO
H
H
H
H-H
H-TT-T
T-H
Heterodimers were major products with 60%.
1H NMR analysis of the photoproduct mixture isolated using biphasic extraction showed the presence of four distinct pseudo-triplet signals of equal intensity un the cyclobutane region (3-5ppm). The signals were present alongside the syn H-H homodimers of cinamic acid and 6-methyl coumarins which are known to be formed within γ-CD.
The pseudo-triplets correspond to the multicity pattern of cyclobutane skeleton with non-equilvalent protons, as is expected in a heterodimer.
2.53.03.54.04.55.05.56.06.57.07.5 ppm
2.53.03.54.04.55.05.56.06.57.07.5 ppm
* *• •
^ ^ ^ ^ #
No cyclodextrin
g-cyclodextrin
Computational Studies
COSY analysis
OHO
O O
OH
OO O h
-CD inclusion complex
hμ
g-CD
What drive the formation of hetero-guest pair complex?
Steric complementary directs the formation of hetero-guest within the cavity. The H-H dimer was compact
enough to fit both the aromatic rings within the cavity
Other heterodimers consist of aromatic rings that are spaced much father away to be simultaneously included within the cavity.
The complex formation is based on the ability of the hydrophobic moieties to avoid aqueous environment outside cavity.
What if other substitutes attached to the
ring of guest?
- One guest possessed a bulky group heterodimer is present in proportions much higher than both the homodimers combined.
O OH
O
OO OH
O
OO OH
O
O
O OH
O
O
H3CO
O OH
O
O
H3CO
O OH
O
O
O OH
O
OO OH
O
OO OH
O
O
O OH
O
O
H3CO
O OH
O
O
H3CO
O OH
O
O
3-methylcinnnamic acid and coumarin
3-methoxycinnamic acid and coumarin
Both guests had a bulky substituent
O OH
O
OO OH
O
OO OH
O
O
O OH
O
O
H3CO
O OH
O
O
H3CO
O OH
O
O
3- methoxycinnamic acid and 6-methyl coumarin
The proportion of the heterodimer was significantly lower than that if homodimers.Reason: No complementarity in
this combination, so no significant driving force for selective formation 1:1:1.
The spatial complementarity could have a strong influence in governing the proportion of homo and hetero guest pair complexes
.
How about electron withdrawing substitutes?
O OH
O
O
Cl
O OH
O
O
Cl
O OH
O
O
Br
O OH
O
O
Br
O OH
O
O
Cl
O OH
O
O
Cl
O OH
O
O
Br
O OH
O
O
Br
Using alkene pairs which differed in their electronic properties to see influence of electronic effect.
Reason: Electron withdrawing chlorine atom in CAs which enables them to engage in a stabilizing weak interaction with CU and 6-MeCU.
51% homodimer
63% homodimer
Are there any differences between halogenated substitutes?
O OH
O
O
Cl
O OH
O
O
Cl
O OH
O
O
Br
O OH
O
O
Br
44% homodimer
O OH
O
O
Cl
O OH
O
O
Cl
O OH
O
O
Br
O OH
O
O
Br48% homodimer
Heterodimer is still the major product though their proportion was not as high as in case of chlorine.
No significant difference between the 3-Br CA-CU and 3-Br CA-6-MeCU.
The size of halogen substitutes influence the formation of complex.
The higher percent of product could be attributed to the electronic factor.
Weak electronic interaction between the aromatic rings of the alkene pairs could be strong enough to govern the inclusion complex arrangement to favor the formation of hetero-guest pair complex
Photodimerization between cinnamic acid esters in
the γ-CD cavity
O
OO
O
2014-Dec-13 - Methyl-cinnamate within g-CD.001.esp
4.55 4.50 4.45 4.40 4.35 4.30 4.25 4.20 4.15 4.10 4.05 4.00 3.95 3.90 3.85Chemical Shift (ppm)
O
O
O
O
O
O O
O
O
O
CD inclusion complex
h
O
O
O
O
CDCl3
57%37%
Conclusion
γ-CD could be used to to effect selective photo-heterodimerization between non-identical alkenes.
Steric and electronic govern complex distribution.
Steric effect appears to be the leading factor
Selectivity of the syn Head-Head arrangement is favored
Future directions
• Understanding the interactions between alkenes basing on their specific properties and take advantage of special characteristics of cavitand can perfectly create any special complexes for essential applications.
• Exanimate how other substitutes can change the properties of complexes.
• To obtain complete characteristics and configuration of complexes
• Advance other properties in complexes such as energy.
Acknowledgements
I want to thank Dr. Pattabiraman for his mentorship and encouragement during making my project. Thank you for starting my interest in research.
I want to thank Aspens Clements for experimental support.
ReferencesPattabiraman, M., & Clements, A. (2014). Journal of photochemistry and photobiology A: Chemistry. G-Cyclodextrin Mediated Photo-heterodimerization between Cinnamic Acids and Coumarins, 297(2014) 1-7.Pattabiraman, M., Natarajan, A., Kaanumalle, L., & Ramamurthy, V. (2005). Templating Photodimerization of Trans-cinnamic Acid with Cucurbit[8] and G-cyclodextrin, 7(529-532).Maddipatla, M., Pattabiraman, M., Natarajan, A., Srivastav, K., Mague, J., & Ramamurthy, V. (2012). Organic and Biomolecular Chemistry. Regioselective Photodimerization of Pyridyl-butadienes within Curcubit[8]uril Cavities, 2012,10,9219.