This PDF presentation describes briefly my research experiences in synthetic organic and analytical chemistry. The time period of these research projects range from 09/2006 to 06/2015. All the projects were carried out at various academic institutes/university in the Czech republic and Poland. Time period, place of work and position were mentioned at the first slide of individual project. To noted that all the experimental synthesis, separation/purification, characterization and applied analytical experiments were performed independently by me.

1. Place of work:
University of Wroclaw,
Wroclaw, Poland
15/01 - 15/05/2015
(1%)

2. 21
5, 20
o- tol
p-Me
7, 8
17, 18
12, 13
2, 3
NH
m- tol
Figure. 1H NMR spectrum of 10,15-Ditolyl-21-carbachlorin 4 in CDCl3.
HR-MS(ESI+): m/z calcd for C35H29N3+ H+: 492.2440; found 492.2460

3. 3
Modified cucurbit[n]urils:
Synthesis and supramolecular interactions
Ph.D. Defense Presentation
Date: 1st October 2012
Place of work: Department of Chemistry,
Masaryk University Brno, Czech Republic
09/2006 - 09/2012

4. 4
Chemical structure of cucurbit[n]uril and the reactive sites of it’s modification?
Sites for functionalization
CB[n]: Cucurbit[n]uril
(n = 5-8, 10)
Glycoluril
(Building block of CB[n])
Cucurbit[6]uril
Peripheral (equatorial) position
Methylene bridge (axial) position
, 100°C,
24 h
1. Kim, J.; et. al. J. Am. Chem. Soc. 2000, 122, 540-541. 2

5. 5
1. Extremely low solubility in common organic/aqueous solvents
(except for aqueous solution of strong acids).
2. Problem of accessing CB[n] derivatives/analogues by tailor-made synthetic procedures
What are the limitations in the CB[n] chemistry ?
1. To prepare functionalized CB[n] compounds.
2. To improve their solubility in both aqueous and organic solvents.
3. To access their wide range of applications.
Why is modification of CB[n] compounds necessary ?

6. 6
Methods of preparing functionalized cucurbit[n]uril: Three possible routes
2. Kim, K.; et. al. Chem. Soc. Rev., 2007, 36, 267-279.
Route 1
Route 2
Direct method of
functionalization
Indirect method of
functionalization
Route 3
Indirect method of
functionalization
Substitution at the peripheral position
Substitution at the CH2 bridge position
(so far found to be unsuccessful)
Substitution at the peripheral position

7. 7
Research aims of this dissertation work
Two major projects
Project 1
Synthesis and separation of new
monosubstituted CB[6]
compounds modified at the CH2
bridge (axial) position.
Project 2
Synthesis, purification and supramolecular interactions of a water soluble CB[6] derivative,
namely, hexamethylcucurbit[6]uril (MeCB[6]).
Here, different pyridinium guests (G1, G3, G4) were used to study their supramolecular
complexations with the MeCB[6] macrocycle both in the solution and solid state.

8. Scheme. Reaction Scheme for Synthesis of Monosubstituted CB[6]
Figure. X-ray crystal structure of Monosubstituted CB[6]
3. L. Gilberg, M. Shamsul Azim Khan, M. Enderesova, V.Sindelar. Organic Letters, 16 (9), 2446-2449, 2014.
Project 1: Synthesis of monosubstituted CB[6]
(0.2%)

9. N N
NN
O
O
N N
NN
O
O
C
H
C
H2
5
1
I-01
3. L. Gilberg, M. Shamsul Azim Khan, M. Enderesova, V.Sindelar. Organic Letters, 16 (9), 2446-2449, 2014.

10. 10
Project 2: Synthesis of hexamethylcucurbit[6]uril (MeCB[6]) and its
supramolecular interactions with different pyridinium guests
4. Khan, M.S.A.; Heger, D., Necas, M.; Sindelar, V. J. Phys. Chem B. 2009, 113, 11054-11057.
X-ray crystal structure of MeCB[6]•acetone•19H2O complex
The “acetone molecule” was not
possible to remove completely
from MeCB[6] cavity even after
drying at 100 °C for 24 h.

11. 11
Figure. 1H NMR spectrum (500 MHz, D2O) of pure hexamethylcucurbit[6]uril, MeCB[6].
4. Khan, M.S.A.; Heger, D., Necas, M.; Sindelar, V. J. Phys. Chem B. 2009, 113, 11054-11057.

12. 12
Supramolecular interactions of MeCB[6] with pyridinium guests (G1, G3, G4)
Two different modes of interaction between MeCB[6] and the pyridinium guests were
studied
1. Binding mode in the solid state (using X-ray crystallography)
2. Binding mode in the solution using
a) 1H NMR titration method
b) UV-vis spectrophotometric titration method

13. 13
Supramolecular interactions of MeCB[6] with methylviologen (MeV2+ = G1) guest
4. Khan, M.S.A.; Heger, D., Necas, M.; Sindelar, V. J. Phys. Chem B. 2009, 113, 11054-11057.
Binding mode between MeCB[6] and MeV2+in the pure D2O solution: 1H NMR fast exchange kinetics
NN CH3
CH3
+ +
Crystal preparation of
MeCB[6]•MeV2+•8H2O complex
Slow evaporation of aqueous
solution of the host and guest in 1:1
ratio resulted X-ray quality single
crystals.
Binding mode between MeCB[6] and MeV2+in solid state: X-ray crystallography - wireframe model
Methyl protons of MeV2+ (red ●), MeCB[6] (green ▲), and acetone (blue ♦).
α β
β
α
β α
α β
(A)
(B)
(C)
Free MeV2+
0.5 : 1
1 : 1
MeCB[6]: MeV2+

14. 14
Determination of binding constants (K / M-1) for the complexation between MeCB[6] and
methylviologen (MeV2+) guest : UV-vis spectrophotometric titration method
4. Khan, M.S.A.; Heger, D., Necas, M.; Sindelar, V. J. Phys. Chem B. 2009, 113, 11054-11057.
Figure. Electronic absorption spectrum of the
complexation between MeV2+ and MeCB[6] in
pure water.
P S I - P l o t W o r k i n g D e m
w w w . p o l y s o f t w a r e . c o m
P S I - P l o t W o r
w w w . p o l y s o f
P S I - P l o t W o r k i n g D e m
w w w . p o l y s o f t w a r e . c o m
P S I - P l o t W o r
w w w . p o l y s o f
P S I - P l o t W o r k i n g
w w w . p o l y s o f t w a r e
P S I - P l o t
w w w . p o l
P S I - P l o t W o r k i n g
w w w . p o l y s o f t w a r e
P S I - P l o t
w w w . p o l
Legend
0.1mM NaCl
fit1
0.5mM
fit2
1mM
fit3
3mM
fit4
5mM
fit5
10mM
fit6
20mM
fit7
P S I - P l o t W o r k i n g D e m o
w w w . p o l y s o f t w a r e . c o m
P S I - P l o t W o r k i n g D e m o
w w w . p o l y s o f t w a r e . c o m
P S I - P l o t W o r k i n g D e m o
w w w . p o l y s o f t w a r e . c o m
P S I - P l o t W o r k i n g D e m o
w w w . p o l y s o f t w a r e . c o m
P S I - P l o t W o r k i n g D e m o
w w w . p o l y s o f t w a r e . c o m
P S I - P l o t W o r k i n g D e m o
w w w . p o l y s o f t w a r e . c o m
P S I - P l o t W o r k i n g D e m o
w w w . p o l y s o f t w a r e . c o m
P S I - P l o t W o r k i n g D e m o
w w w . p o l y s o f t w a r e . c o m
c(MeCB[6]) in mol / L
0.0000 0.0001 0.0002 0.0003 0.0004
Absorbanceat257nm(a.u.)
0.40
0.45
0.50
0.55
0.60
0.65
0.70
0.75
0.80
Effect of NaCl on the binding constant K
Figure. Fitting of the absorbance data for the 1:1 complex
formation between MeV2+ and MeCB[6].
257 nm
K = (2.05 ± 0.21) × 105 M-1
MeCB[6]
concentration
increases

15. Table: Values of Association Constants of the MeCB[6]-MeV2+ Complex (KMeCB[6]) and the
CB[7]-MeV2+ Complex (KCB[7]): UV-vis Spectrophotometric and 1H-NMR Titration methods
4. Khan, M.S.A.; Heger, D., Necas, M.; Sindelar, V. J. Phys. Chem B. 2009, 113, 11054-11057.
NaCl/mM KMeCB[6] / M-1 KCB[7] / M-1
0 (1.23 ± 0.15) × 105c Ndd
0 (2.05 ± 0.21) × 105 (1.68 ± 0.30) × 106
0.1 (1.97 ± 0.13) × 105 ndd
0.2 (1.03 ± 0.06) × 105 ndd
0.4 (6.85 ± 0.43) × 104 ndd
0.5 (7.17 ± 0.45) × 104 ndd
0.8 (3.15 ± 0.28) × 104 ndd
1 (2.84 ± 0.31) × 104 ndd
2 (2.47 ± 0.21) × 104 ndd
3 (1.17 ± 0.12) × 104 ndd
5 (3.76 ± 0.35) × 103 ndd
10 (2.15 ± 0.20) × 103 (8.3 ± 1.8) × 105
20 (7.6 ± 1.4) × 102 ndd
30 (3.02 ± 0.55) × 102 ndd
40 (1.25 ± 0.63) × 102 ndd
50 (1.00 ± 0.67) × 102 (3.45 ± 0.52) × 105
100 nbb (1.49 ± 0.16) × 105
200 (6.0 ± 2.5) × 101c (9.4 ± 1.0) × 104
a The standard deviation of the fit is given for each measurement. b K not obtained by
UV-vis spectroscopy. c Determined by 1H NMR titration. d Not measured.
CB[7]•MeV2+ complex
NN CH3
CH3
+ +
MeCB[6]•MeV2+ complex
> 2000-fold
decrease
only 5-fold
decrease

16. 16
Table: Values of Association Constants (K/M-1): UV-vis Spectrophotometry
Unpublished results: KMeCB[6]●G3 and KMeCB[6]●G4
5. Kolman, V.; Khan, M.S. A.; Babinský, M.; Marek, R.; Sindelar, V. Org. Lett. 2011, 13, 6148-6151.
K / M-1
NaCl / M MeCB[6]∙G1 MeCB[6]∙G3 MeCB[6]∙G4
0 (2.05 ± 0.21) × 105 (3.47 ± 1.95) × 107 (9.79 ± 3.63) × 107
0.005 (3.76 ± 0.35) × 103 (7.41 ± 1.78 ) × 106 -
0.01 (2.15 ± 0.2) × 103 (2.04 ± 1.32) × 106 (1.65 ± 1.51) × 107
0.02 (7.60 ± 1.40) × 102 (1.05 ± 1.30) × 106 (2.28 ± 1.05) × 106
0.03 (3.02 ± 0.55) × 102 (4.79 ± 1.23) × 105 (1.15 ± 1.12) × 106
0.04 (1.25 ± 0.63) × 102 (2.75 ± 1.17) × 105 (1.08 ± 1.2) × 106
0.05 (1.0 ± 0.67) × 102 (1.95 ± 1.12) × 105 (4.19 ± 1.23) × 105
(2.10 ± 0.20) × 106 *
0.1 n.d (6.46 ± 1.40) × 104 (3.09 ± 1.35) × 105
0.2 (6.0 ± 2.5) × 101 ** (4.20 ± 2.0) × 104 (7.88 ± 1.26) × 104
0.3 - (3.31 ± 1.82) × 104 (8.8 ± 1.12) × 103
* value for the complex with CB[6], ** 1H NMR titration method
Figure. Structures of host (MeCB[6])
and guests (G1, G3, G4)
M-1 : 2.1 × 105 < 3.5 × 107 < 9.8 × 107
Extra stabilized: one
hydrogen bond
(+N-H···O), ion-dipole
interactions
Extra stabilized due
to hydrophobicity of
ethylene moiety
Different binding mode of pyridinium
guests inside MeCB[6] cavity

17. Collaborative project: Deprotection of propylene bridged glycoluril dimer
6. Stancl, M.; Khan, M.S.A.; Sindelar, V. Tetrahedron, 2011, 67, 8937-8941.
Figure. Chemical structures of mono- (A), di- (B), tri- (C) and tetra- (D) hydroxy- bis(propylene)glycoluril dimers.
N N
NN
O
O
N N
NN
O
O
NH N
NNH
O
O
N NH
NHN
O
O
K2
S2
O8
/ H2
O
(Glycoluril dimer, Yield: 37.4 %)Bis(propylene)glycoluril dimer
N2 atm / 78°C, 6h
Characterization: 1H, 13C NMR (d6-DMSO) spectroscopy and HRMS (ESI+)

18. 0,1
0,15
0,2
0,25
0,3
0,35
0 0,00001 0,00002 0,00003 0,00004 0,00005
Conc. of CB6 / M
Absorbanceat317nm
CB6·2 complex (1:1) at 0.05 M NaCl
K = (2.1 ± 0.2) × 106 M-1
UV-vis titration method
Figure. 1H NMR spectra (300 MHz, 0.05 M NaCl-D2O)
5. Kolman, V.; Khan, M.S. A.; Babinský, M.; Marek, R.; Sindelar, V. Org. Lett. 2011, 13, 6148-6151.
Guest G4
0.5 : 1
1 : 1
CB6●2
Slow exchange process in the 1H NMR time scale
Collaborative project: Supramolecular shuttle based on CB6 and guest 2 (BPE)
Figure. Structures of synthesized host (CB6)
and guest 2 (BPE).

19. Calix[n]phyrin chemistry
Place of work: (current position- Postdoctoral fellow)
University of Chemical Technology Prague, Czech Republic
05/2013 - 06/2015

20. 1. Synthesis of calix[n]phyrin conjugates with Tröger's bases (TB).
2. sensing of cations /anions of the synthesized compounds.
Research goals
Calix[4]phyrin-TB conjugate
V shape

21. Synthesis of bis-(nitro)calix[4]phyrin

22. Tb
Tc
Td
Te
Cb Cc
Cd
Ce
Ta
Ca
Tb
Cb
Tc
Cc
Cd
Ce
Td
Te
Tf
Cf
Figure 2: 1H NMR spectrum of Bis(nitro)calix[4]phyrin, 2a (cis-isomer, green)
and 2b (trans-isomer, red) in CDCl3.

23. Synthesis of TB-calix[4]phyrin and TB-calix[6]phyrin

24. 2 x NH
18 x CH: TB
8 x CH: pyrrole
6 x CH2: CB
4 x CH3
3 x NH
27 x CH: TB
12 x CH: pyrrole
9 x CH2: TB
6 x CH3
A) TB-calix[4]phyrin, 8a
B) TB-calix[6]phyrin, 8b
Compound 8a: HRMS-ESI+: for [M+H]+ (C62H53N8) calcd: 909.44; found 909.44 and for
[M+2H]2+ (C62H54N8) calcd: 455.22; found 455.22
Compound 8b: HRMS-ESI+: for [M+H]+ (C93H79N12) calcd: 1364.66; found 1364.66 and for
[M+2H]2+ (C93H80N12) calcd: 682.83; found 682.83

25. Tris-mannose methylamine
Supramolecular object
Construction of supramolecular host from TB

26. Synthesis of tris-mannose cluster from D(+)-mannose

28. Cyclodextrin chemistry - dimerization of cyclodextrins
Place of work: (Position- Research assistant)
Institute of Organic Chemistry and Biochemistry, Prague,
Academy of Sciences of the Czech Republic
08/2011 - 12/2012

29. Concept: Duplex Cyclodextrins Connected with Reversible Linkages
Guest
Duplex CD
Cleavage by external stimuli
Guest
release

30. 2 R1–SH
H2OO2
pH ≥ 7
R2–S R1–S–S–R1
+ R1–S + R1–S–S–R2
Concept: Duplex Cyclodextrins Connected with Disulfide Linkages

31. • Synthesis of cyclodextrin homoduplexes and heteroduplexes linked by disulfide bonds
Cyclodextrin Duplexes Linked by Disulfide Bonds - Outline
• Dynamic exchange of building blocks in the presence of a guest (template effect)
• Thermodynamic stabilities of inclusion complexes with organic molecules
• Cleavage of disulfide bonds by reducing thiols
• Applications in supramolecular / material chemistry

32. 5 steps, 69 %
5 steps, 65 %
J. Org. Chem. 2009, 74, 1082.
α-CD
O
OH
OHO
O
OH
OH
AcS O
O OH
OH
OH
O
O
O
OH
OH
O
OH
OH
SAcO
OOH
OH
OH
O
OH
OH
β-CD
O
OH
OH
O
O
OH
OHAcS
O
O
OH
OH
OH
O
O
OH
OH
OOH
OH
SAc
O
O
OH
OH
OH
O
OH
OH
O
OHOH
OH
O
O
Starting Cyclodextrin Disulfanyl Building Blocks
Figure. Gradient parameters for the elution of the mixture reaction of
β-cyclodextrin heteroduplex formation (volume of each collected fraction was 39 ml).
= =

35. Synthesis of 3-hydroxyadamantane-1-acetamidohexanol in dry DMF
Figure. Chromatograms of βCD-
heteroduplex: A) in equimolar
mixture with the template (guest),
and for the synthesis of βCD-
heteroduplex B) without template,
and C) with template. The solvent
system in HPLC analysis was 22-60%
MeOH-water (30 min).
A
B
C
Host : template; 1:1
Host: no template
Host: with template

37. Dimerization of Bifunctional Cyclodextrins by Oxidation of Sulfanyl Groups
[O]

38. Duplexes with Cleavable Bonds for Drug Delivery

39. Monolayers on Glass Surfaces Using Cyclodextrin Hetroduplexes
as Divalent Connectors

40. 5.7 Å
7.8 Å
~ 14 Å
Monolayers on Glass Surfaces Using Cyclodextrin Hetroduplexes
as Divalent Connectors

41. Si / glass
H2SO4
H2O2
activation
α
β
(15 min, drops)
SAM: preparation
μCP
(5 min,
3x5 µm, lines)
Rh-Ad3

42. lissamin-Ad3 (Rh-Ad3)
excitace: 510-550 nm
emise: 590 nm (červená)
3.5 μM, voda/EtOH (1:1)
Fluorescent Trivalent Ligand

43. Fluorescence microscopy

44. Duplexes for Selective Sensors