The document outlines multiple research projects in chemistry, focused on the synthesis and characterization of organic compounds, including Schiff bases and bisphosphonates, for pharmacological applications such as cancer treatment. It includes detailed descriptions of various methodologies used in synthesis, characterization techniques, and the exploration of supramolecular interactions with modified cucurbiturils. The work culminated in several published articles illustrating the findings and contributions to the field of organic chemistry and materials science.

1. 1
M.Sc. Thesis research project (1999 - 2000)
Place: Department of Chemistry (synthetic organic gr.) , Jahangirnagar University, Savar - 1342, Dhaka, Bangladesh.
Title: Synthesis of Schiff bases, thiadiazoline derivatives and some heterocyclic compounds as probes for
pharmacological studies especially as Anticancer agents
Published articles
1. Synthesis of aldehyde- ∆
2
-1, 3, 4 -thiadiazoline heterocycles.
Journal of the Bangladesh Chemical Society, 16(2), 124-132, 2003.
2. Synthesis of aldehyde schiff bases of 4-amino-1,2,4-triazine-3-thione and p-substituted phenylthiazolyl derivatives.
Journal of The Bangladesh Chemical Society, 17(1), 52-58, 2004.

2. 2
UNESCO - IUPAC research project (Jul’2004 - Oct’2005)
Place: Institute of Macromolecular Chemistry, Academy of Science of the Czech Republic, Prague 6.
Topic: Functionalized bisphosphonic acids for surface modification of magnetic iron oxide and other metal oxides
EUROGREENPOL- In book of proceedings p.27-32. First european summer school on green chemistry of polymers,
Iasi, Romania, 21-27 August 2005.
Abstract
The aim of this work was to modify the surface of magnetic oxide nanoparticles such as magnetite- Fe3O4,
maghemit-γFe2O3, ferrites MeO.Fe2O3 where Me: Cu, Co, Mn. Recently modified magnetic oxides have
been reported to have wide range of applications like immobilization of biopolymers (antibodies, enzymes,
proteins, nucleic acids etc), magnetic resonance imaging, bone and tissue repair (as bisphosphonates have
high affinity for hydroxyapatite), cancer treatment by hyperthermia, site-specific delivery of drugs, gene
delivery to cells and so on. To fullfill these properties we synthesized and characterized various kinds of
bisphosphonates (I - III) with additional functional groups such as -NH2, OH, CH=CH2, -NH-NH2, halogen,
PEG, polymer etc. in the molecules.
A. Direct synthesis of 1,1-bisphosphonate (type I)
Examples: H2N(CH2)6COOH, Br(CH2)6COOH etc.
The aim of the above synthesis is to introduce H2N-NH (hydrazine) group at the end of bisphosphonic acid which is
important for immobilization of biopolymers, chelating group for specific sorption of cations etc.
CH2=CHCOOC2H5 H2NNH2.H2O+
reflux,5.5 hrs
N
NO
H
H
EtOH
aq.KOH soln.i.
ii. neutralize, Conc.HCl
H2NNHCH2CH2COOH
3-hydrazinopropionic acid
Pyrazolidin-3-one
OH
OH
P
O
OH
OH
P
O
OH
OH
OH
P
O
OH
OH
P
O
R3H
OH
OH
P
O
N
OH
OH
P
O
R1 R2
I II III
R(CH2)nCOOH
PCl3, H3PO3
reflux, 70C, 21 hrs
CH3SO3H
i.
ii.
R(CH2)n C
P(O)(OH)2
P(O)(OH)2
OH
H2O (type I)

3. 3
B. Michael addition reaction of ethylenebisphosphonate (type II)
C. Direct synthesis of α-aminophosphonic acid (type III): Mannich-type reaction
D. Incorporation of bisphosphonate moiety in the polymer chain: free radical reaction
H2C CH[P(O)(OH)2]2
N(H2CCH2OH)2
H2C=C[P(O)(ONa)2]2 HN(CH2CH2OH)2+
CH3COOH, H2O
reflux,110-120C, 11hrs
i.
ii. Cation exchanger,
2(N)H2SO4
H2C=C[P(O)(ONa)2]2 H2C=C[P(O)(OH)2]2 H2C=C[P(O)(OCH3)2]2
H2C CH[P(O)(OCH3)2]2
N(H2CCH2OH)2
H2C CH[P(O)(OK)2]2
N(H2CCH2OH)2
H2C CH[P(O)(OH)2]2
N(H2CCH2OH)2
Cation exchanger excess HC(OCH3)3
relux, 60-65 C
and then 106 C
HN(CH2CH2OH)2
relux, 65-76 C,11 hrs
KOH, EtOH
relux, 85C, 6hrs
Cation exchanger
Example: CH2=CHCH2NH2 ;
R N
CH2
CH2 P(O)(OH)2
P(O)(OH)2
RNH2 + aq.HCHO +H3PO3
Conc.HCl, H2O
reflux,105C,3.5 hrs
O2N.C6H5NH23
H2N O SO3H HN[CH2P(O)(OH)2]2+
reflux, 100-107C, 2 hrs
H2O
H2NN[CH2P(O)(OH)2]2
OH
OH
HO
HCHO ; HN[CH2P(O)(OH)2]2
reflux,73-78C, 2hrs
CH3COOH ; H2O OH
OH
HO
CH2N[CH2P(O)(OH)2]2
Pyrogallol
(type III)
(type II)
(type II)
H2C CH N[CH2P(O)(OH)2]2CH2
CH2=CHCONHCH(CH3)2CH2=C[P(O)(ONa)2]2
CH2=C[P(O)(OH)2]2
i.
ii.
iii.
(NH4)2S2O8,
75C, 24 hrs
Block copolymer of NIPAAm and
the corresponding diphosphonic acid
i.
CH2=C[P(O)(ONa)2]2
H2C CH N[CH2P(O)(OH)2]2CH2
PEG 4000
Ce(iv)(NH4)NO3
N2 atm,30 C, 3 hrs
Block/graft copolymer of PEG and
the corresponding diphosphonic acid
ii.

4. 4
Terminology:
PEG 4000 = Polyethylene glycol( mol. Wt . 4000)
NIPAAm = N-Isopropylacrylamide
HN[CH2P(O)(OH)2]2 = imidodi(methylenephosphonic acid)
H2N-O-SO3H = hydroxylamine-O-sulfonic acid
HN(CH2CH2OH)2 = diethanolamine
Ce(iv)NH4NO3 = Ceric ammonium nitrate (used as redox initiator)
(NH4)2S2O8 = Ammonium persulfate (used as free radical initiator)
HC(OCH3)3 = trimethyl orthoformate
H2NNH2.H2O = Hydrazine monohydrate
H2N(CH2)6COOH , Br(CH2)6COOH = 6-amino / bromo caproic acid
References
[1] G.R Kieczykowski. J.Org.Chem. 1995, 60 (25), 8310-8312.
[2] M. Lecouvey, Heteroatom Chem. 2000, 11(7), 556-561.
[3] Sergio H. Szajnman. Bioorg. Med. Chem. Lett. 2001, 11, 789-792.
[4] D. Allan Nicholson, W.A. Cilley and O.T. Quimby. A convenient method of esterification of
Polyphosphonic acids. J.Org. Chem.1970, 35(9), 3149-3150.
[5] Charles R. Degenhardt and Don C.Burdsall. Synthesis of Ethylidenebis(phosphonic acid)
and its tetraalkyl esters. J.Org.Chem. 1986, 51(18), 3488-3490.
[6] David W. Hutchinson and David M. Thornton. Michael addition reactions of
ethenylidenebisphosphonates. J. Organomet. Chem. 1988, 346, 341-348.
[7] Kurt moedritzer and Riyad R. Irani. The direct synthesis of α-aminomethylphosphonic
acids. Mannich type reactions with orthophosphoric acid. J.Org.Chem. 1966, 31, 1603-1607.
[8] Amination of Tertiary Amines by Hydroxylamine-O-sulfonic Acid. J. Org. Chem. 1959, 24, 859.
[9] Synthesis of Block copolymers via redox polymerization. J. Appl. Polym. Sci. 1999, 71, 1385-1395.
[10] Shigeo Nakamura, Masato Amano, J. Polym. Sci., Part A: Polym. Chem., 1997, 35, 3359-3363.
4. Synthesis of 1,1′-binaphthalene-2,2′-diamine based ligand for enantioselective recognition of chiral
carboxylate anions
NH2
NH2
CF3
CF3OCN
N
H
N
H
O
O
N
H
N
H
CF3
CF3
CF3
CF3
1, 2, 3
+
1. Dry CH2Cl2, 28°C, 20 h,
2. quench with distilled methanol, stir 20 h
3. column chromatography P.E: DCM, 1:1, 100% DCM
(R)-(+)-1,1-binaphthalene
-2,2- diamine
3,5-bis(trifluoromethyl)
-phenylisocyanate
(R)-2,2′-Bis{N-[3,5-bis(trifluoromethyl)
phenyl]ureido}-1,1′-binaphthalene

5. 5
ABSTRACT - Ph.D Thesis (Sept, 2006 – Jul, 2011)
Place: Department of Chemistry, Masaryk University in Brno, Czech Republic (EU).
Ph.D thesis title: Modified cucurbit[n]urils: synthesis and supramolecular interactions
There has been a remarkable development in the cucurbit[n]uril (CBn, n = 5-10) chemistry since the
last decade. The development outcomes also inspired us to contribute efforts to this rapidly growing
topic. The very common feature of the parent CBn and their homologues is the limited solubility or
insolubility in common solvents (except in aqueous acid media) which limits their applications.
That’s why modification of the parent CBn with suitable substituents is required to facilitate their
solubility in solvents like water, DMSO, methanol, acetonitrile etc.
Figure 1. Unsubstituted CB6 (n = 6)
First project of this thesis was dealt with the syntheses and characterizations (1
H NMR, 13
C NMR
and MALDI-TOF MS) of a series of monosubstituted CB6 having a substitutent at the methylene
bridge (axial) position of CBn by reacting glycoluril with various aldehydes (RCHO). I developed
new purification method for a monosubstituted CB6 substituted at the methylene bridge position
(Figire 2. I-01).
Figure 2. Monosubstituted CB6 (n = u+s = 5+1 = 6)
Second project was dedicated to the synthesis, improved purification, characterization and to study
supramolecular properties of a robust water soluble macrocyclic receptor,
hexamethylcucurbit[6]uril (MeCB6). Good solubility of MeCB6 in pure water allowed us to study
its supramolecular interactions with the synthesized guests II.1 - II.10 using sophisticated
techniques like FT-NMR, UV-vis spectrophotometry, VP-ITC, MALDI-TOF MS and X-ray
N N
NN
O
O
N N
NN
O
O
C
H
C
H2
5
1
I-01

6. 6
diffraction. We determined the binding modes of these guests in solution using 1
H-NMR technique
and studied elaborately the effect of NaCl on the binding affinities (K /M-1
) of MeCB6 with them.
Binding modes of MeCB6 with guests in the solid state were studied by preparing new X-ray
quality single crystals of several inclusion complexes of MeCB6 with the guests.
NH N
NH3
NH3
NH3
NH3
NH3
NN
NN
NN
N
N
H3
N
NH3
I2
I2
I2
I2
-.
N N CO2
HHO2
C
NH3
H3
N
.2Cl
-
+
+
NH3
-.Cl
+
. -
I
N N
N N
I2
+
II.3a
II.3b
II.3c
II.4
II.5
II.6a
II.6d
II.6b
II.6c
II.6e
II.7
II.8
II.9
1
6
71
1
8
1
2
4
1
2
4
1
2
4
2
2
1
1
4
4
+
+
+
+
+
-.Cl
+ +
++
+ +
+
+
+
+
-.
-.
-.
-.Br
-.Cl
-.Cl
-.Cl
-.Cl
-
.2Cl
II.10
++
-
.2Br
II.2
+
II.1
++
-.
Figure 3. Structure of hosts (CB6, CB7 and MeCB6) and guests (II.1 - II.10) used in the study.
Published articles
1. V. Kolman, M. Shamsul Azim Khan, M. Babinsky, R. Marek, V. Sindelar. Supramolecular Shuttle
Based on Inclusion Complex between Cucurbit[6]uril and Bispyridinium Ethylene.
Organic Letters, 13 (23), 6148-6151, 2011. (IF 5.862, 2011)
2. M. Stancl, M. Shamsul Azim Khan, V. Sindelar. 1,6- Dibenzylglycoluril for Synthesis of Deprotected
Glycoluril Dimer.
Tetrahedron, 67, 8937-8941, 2011. (IF 3.025, 2011)
3. M. Shamsul Azim Khan, D. Heger, M. Necas, V. Sindelar. Remarkable salt effect on stability of
supramolecular complex between modified cucurbit[6]uril and methylviologen in aqueous media.
Journal of Physical Chemistry B, 113 (32), 11054-11057, 2009. (IF 4.19, 2009)
CB6 CB7
MeCB6

7. 7
Post-doctoral research project (Aug, 2011 to Dec, 2012)
Place: Institute of Organic Chemistry and Biochemistry, Academy of Science of the Czech
Republic, Prague 6.
Project Title: Synthesis of cyclodextrin heteroduplexes and study of their supramolecular properties
Note: Results will be published after gathering some more results.

8. 8
Synthesis of the compounds 5 and 6 from the starting reactant α-cyclodextrin (α-CD): 6 steps
O
OH
HO OH
O
O
OH
OH
OH
O
O
OH
OH
HO
O
O
O
OH
OH
HO
O
OH
HO
HO
O
O
OHHO
OH
O
O
OBn
BnO OBn
O
O
OBn
BnO
OBn
O
O
OBn OBn
BnO
O
O
O
OBn
OBn
BnO
O
OBn
OBn
BnO
O
O
OBnBnO
OBn
O
O
OBn
BnO OH
O
O
OBn
OBn
OBn
O
O
OBn OBn
BnO
O
O
O
OBn
OBn
HO
O
OBn
BnO
BnO
O
O
OBnBnO
OBn
O
O
OBn
BnO Br
O
O
OBn
BnO
OBn
O
O
OBn OBn
BnO
O
O
O
OBn
OBn
Br
O
OBn
OBn
BnO
O
O
OBnBnO
OBn
O
O
OH
HO Br
O
O
OH
OH
OH
O
O
OH OH
HO
O
O
O
OH
OH
Br
O
OH
HO
HO
O
O
OHHO
OH
O
O
OH
HO SCOCH3
O
O
OH
OH
OH
O
O
OH OH
HO
O
O
O
OH
OH
H3COCS
O
OH
HO
HO
O
O
OHHO
OH
O
O
OH
HO SH
O
O
OH
OH
OH
O
O
OH OH
HO
O
O
O
OH
OH
HS
O
OH
HO
HO
O
O
OHHO
OH
O
1
23
4 5
6
α-CD
Compound 5 ≡
a
c
d
e
f
b

9. 9
Reaction conditions: [a] i. NaH, BnCl, dry DMSO, Ar atm, RT, 18h, ii. hydrolysis with MeOH;
[b] i. DIBAL-H, 50°C, Ar atm, ii. hydrolysis; [c] CBr4, Ph3P, DMF, 60°C; [d] Pd/C, 40 bar, DMF-
EtOH, RT; [e] CH3COSK, DMF, RT; [f] 1 M NaOH, MeOH-H2O, RT.
Synthesis of the compound 11 from the starting reactant β-cyclodextrin (β-CD): 5 steps
Purification method
Compounds 1-6 (for α-CD series) and 7-11 (for β-CD series) were purified using flash
chromatography (compounds 1-3 and 7-9) in acetone-toluene mobile phase and reverse phase
chromatography (compounds 4-6 and 10-11) in methanol-water mobile phase.
β-CD
11
Compound 11 ≡
a - e

10. 10
Synthesis of αβCD- heteroduplex from the compounds 5 and 11: one pot synthesis
Reaction conditions: [g] i. HPLC water, ii. 1 M NaOH, stir at RT for 1 d ; iii. NaHCO3-Na2CO3
aq. buffer (pH = 9), air oxidation, 5 d.
O
OH
HO
OH
O
O
OH
HO
SCOCH3
O
O
OH
OH
OH
O
O
OH
OH
OH
OO
OH
OH
HO
O
O
OH
OH
H3COCS
O
O
OH
HO
HO
O
O
OH
HO SCOCH3
O
O
OH
OH
OH
O
O
OH OH
HO
O
O
O
OH
OH
H3COCS
O
OH
HO
HO
O
O
OHHO
OH
O
11
5
α-CD
β-CD
αβCD - heteroduplex
O
OH
HO S
O
O
OH
OH
OH
O
O
OH OH
HO
O
O
O
OH
OH
S
O
OH
HO
HO
O
O
OHHO
OH
O
O
OH
HO
OH
O
O
OH
HO
S
O
O
OH
OH
OH
O
O
OH
OH
OH
OO
OH
OH
HO
O
O
OH
OH
S
O
O
OH
HO
HO
O
α-CD
β-CD
O
OH
HO S
O
O
OH
OH
OH
O
O
OH OH
HO
O
O
O
OH
OH
S
O
OH
HO
HO
O
O
OHHO
OH
O
O
OH
HO S
O
O
OH
OH
OH
O
O
OH OH
HO
O
O
O
OH
OH
S
O
OH
HO
HO
O
O
OHHO
OH
O
ααCD - homoduplex
α-CD
α-CD
12 13
O
OH
HO
OH
O
O
OH
HO S
O
O
OH
OH
OH
O
O
OH
OH
OH
OO
OH
OH
HO
O
O
OH
OH
S
O
O
OH
HO
HO
O
O
OH
HO
OH
O
O
OH
HO
S
O
O
OH
OH
OH
O
O
OH
OH
OH
OO
OH
OH
HO
O
O
OH
OH
S
O
O
OH
HO
HO
O
ββCD - homoduplex
Two isomers (ββ1 and ββ2)
β-CD
β-CD
14a-b
O
OH
HO
SO
O
OH
OH
OH
O
O
OH OH
HO
O
O
O
OH
OH
S
O
OH
HO
HO
O
O
OHHO
OH
O
O
OH
HO
OH
O
O
OH
HO
SO
O
OH
OH
OH
O
O
OH
OH
OH
OO
OH
OH
HO
O
O
OH
OH
S O
O
OH
HO
HO
O
βCD-intramolecular dithiolαCD-intramolecular dithiol
α-CD
β-CD
16
15
g

11. 11
Compounds 12-16 were separated and purified by Reverse Phase Chromatography with gradient
elution using MeOH-H2O mobile phase system. The isolated compounds were then analyzed by
HPLC using both ELSD and UV detector. The compounds were characterized by 1
H NMR,
MALDI-TOF MS and HR-MS techniques, elemental analysis etc.
Template assisted synthesis of αβCD- heteroduplex from the compounds 5 and 11
O
OH
HO
OH
O
O
O H
HO
SCOCH3
O
O
OH
OH
OH
O
O
OH
OH
OH
OO
OH
OH
HO
O
O
OH
OH
H3COCS
O
O
OH
HO
HO
O
O
OH
HO SCOCH3
O
O
OH
OH
OH
O
O
OH O H
HO
O
O
O
O H
OH
H3COCS
O
OH
HO
HO
O
O
OHHO
OH
O
115
O
OH
HO S
O
O
OH
OH
OH
O
O
OH OH
HO
O
O
O
OH
OH
S
O
OH
HO
HO
O
O
OHHO
OH
O
O
OH
HO
OH
O
O
OH
HO
S
O
O
OH
OH
OH
O
O
OH
OH
OH
OO
OH
OH
HO
O
O
OH
OH
S
O
O
OH
HO
HO
O
α-CD
β-CD
Template that showed strong binding affinity (K =
107
M-1
) with the αβCD- heteroduplex (binding
affinity was prior modelled using computation and
then experimentally measured by isothermal
titration calorimetry)
13

12. 12
Determination of Association Constants (K / M-1
) between various guests and duplex 13 in aqueous
medium using VP-ITC (isothermal titration calorimetry) technique
As guest molecules few organic dyes, fluorescent probe and anticancer drug were used to determine
their binding affinity with the duplex 13.
Computation modelling (using Vina autodock programme) was used to study the possible binding
mode and affinity of each guest inside the 13 cavity before experimental determination of the
binding affinity.
References:
1. The Journal of Organic Chemistry 74: 1082-1092, 2009.
2. Chemistry - A European Journal 18: 12292-12304, 2012.