γ-Cyclodextrin can be used to control the orientation of alkenes and direct photodimerization reactions to form specific cyclobutane products. The study investigated the use of γ-cyclodextrin to direct the photodimerization of cinnamic acid and coumarin derivatives. Steric and electronic complementarity between the alkene guests governed the formation of hetero- versus homodimer complexes within the γ-cyclodextrin cavity. Substituents on the alkenes, like methyl and halogen groups, influenced the proportion of hetero- versus homodimers formed. The head-to-head heterodimer was generally the favored product when steric factors

1. 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

2. Photodimerization
• Photodimerization is a cycloaddition reaction involving two π bonds of two
neighboring molecules.
A
B
A
B
*
A
B
*
A
B
*
A
B
*
A
B
A
B
*
A
A
A
A B
B A
B A
B
(hυ)

3. • 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
t
H
t
t
H
t
t
H

4. Natural products with cyclobutane core have medicinal values
AntinociceptivePulmonary hypertension treatment
Neuroprotector

5. 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.

6. Photo-polymerization
• The complexes are useful in synthesis polymer that
has wide applications in science materials.
Ma, and Tian Acc. Chem. Res. 2014

7. 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
7.5 Å
8.3 Å
7.9 Å

8. 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.

9. 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.

10. 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 O
h
OHO
R
HOOC COOH
HOOC COOH
COOH
HOOC
COOH
HOOC
h
O OO O
O OO O
O
OO
O
O
OO
O
HOOC HOOC
HOOC
O
O O
O
HOOC
O
O
h
h

11. 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

12. 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

13. What happen if 6-methyl coumarin (6-MeCU) is used?
• 6-MeCU with a bulky group compared to un-substituted cinnamic
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-Head
Head-Tail
Tail-Tail
Tail-Head
O O
OH
O
h
-CD
?
Head Tail TailHead

14. 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
H
OH
O
OO
H
H
H
H-H
H-T
T-T
T-H
Heterodimers were major products with 60%.

15. 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

16. COSY analysis
hμ
g-CD

17. 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.

18. 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.
3-methylcinnnamic acid and coumarin
3-methoxycinnamic acid and coumarin

19. Both guests had a bulky substituent
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
.

20. How about electron withdrawing substitutes?
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

21. Are there any differences between halogenated substitutes?
44% homodimer
48% 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

22. Photodimerization between cinnamic acid esters in
the γ-CD cavity
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 3.85
Chemical Shift (ppm)
CDCl3
57%37%

23. 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

24. 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.

25. 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 Aspen Clements for experimental
support.

26. References
Pattabiraman, M., & Clements, A. (2015). Journal of Photochemistry and
Photobiology A: Chemistry. γ-Cyclodextrin Mediated Photo-
heterodimerization between Cinnamic Acids and Coumarins, 297, 1-7.
Retrieved March 10, 2015, from
http://www.sciencedirect.com/science/article/pii/S1010603014004043
Pattabiraman, M., Natarajan, A., Kaanumalle, L., & Ramamurthy, V.
(2005). Organic Letter. Previous Article Next Article Table of Contents
Templating Photodimerization of Trans-Cinnamic Acids with Cucurbit[8]uril
and γ-Cyclodextrin, 7. Retrieved March 10, 2015, from
http://pubs.acs.org/doi/abs/10.1021/ol047866k
Maddipatla, M., Pattabiraman, M., Natarajan, A., Srivastav, K., Mague, J.,
& Ramamurthy, V. (2012). Organic & Biomolecular Chemistry.
Regioselective Photodimerization of Pyridyl-butadienes within
Curcubit[8]uril Cavities, 10(9219). Retrieved March 10, 2015, from
http://www.ncbi.nlm.nih.gov/pubmed/23103970