A.E.Arbuzov Institute of Organic &
Physical Chemistry, Kazan
A.M.Butlerov Chemistry Institute of
Kazan Federal University, Kazan
Supramolecular chemistry of
(thia)calix[4]arenes
I.S.Antipin, S.E.Solovieva, I.I.Stoikov, A.I.Konovalov
Lviv, 6-10 September 2010
V International
VI
Internationalsymposium
symposium“Design
“Designand
Synthesis
of Supramolecular
and
Synthesis
of Supramolecular
Architectures”
St.Petersbourg
12-16 October
September
18-23,2009
2011
Moscow
Kazan
Novosibirsk
http://iopc.ru/butlerov/Index-e.html
Basic principle of supramolecular chemistry
Macrocycles– molecular platform for multipoint
interactions realization and multivalent ligands
design.
Jonathan Swift
Macrocyclic platforms
OH
OH
O
O
OHOH
OH
HO
O
OO
OH
OH
OH
R
X n
OH
Calixarenes
CPKModel
Calyx
HO
HO
X=O, S, NH
S
X X
H H
X X
H H
S
X X
H
H
S
R
H
OH
OH
R
S
X X
H
OH HO
OH HO
R
R
O O
H
H
S
O O
H
H
Calix[4]arenes
V≈10A3
S
O O
H
H
S
S
O O
H
1997 – S.Miyano et al
H
Thiacalix[4]arene
The characteristic advantages of calix[4]arenes for the
constructing of receptors are followed:
H
O
O OO
H H H
O
H
Cone
H
O
H
Partial Cone
H
H
O
O
O
H
H
O
O
O
H
H
1,3-Alternate
H
O
O
H
O
O
H
1,2-Alternate
 the low cost and accessibility of parent macrocycles by one-pot
synthesis;
 calixarenes can incorporate the small hydrophobic organic
molecules into their molecular cavities with the formation of the stable
host-guest complexes;
the existence of variety of calixarene conformations: cone, partial
cone, 1,2-alternate, 1,3-alternate etc.;
 calix[4]arene conformations are rather rigid and are able to fix the
required spatial orientation of binding centers;
 nontoxicity of calixarene platforms.
calixarene platform gives an unique possibility to decorate the upper
and lower rim of macrocycle by the suitable heteroatom groups and to
form the molecular system possessing the several binding centers;
Background of Calixarene Chemistry
Upper Rim
Mono, Di, Tri and Tetra Substituted Derivatives
Cone
S
S
S
OH OH OH OH
Partial Cone
1,3-Alternate
R
S
R
O
Lower Rim
O OO
R R R
O
R
O
R
O
O
R
R
R
O
1,2-Alternate
R
R
O
O
O
O
R
R
O
R
Main Problem:
Stereo and Regio Selective Functionalization of Lower and
Upper Rim
O
O
R
2
Outline
1. Covalent assembly: towards nanosized molecules
hν
“guest
quenching
2. Noncovalent assembly: towards “soft” nanosystems
Functions
+ n
n
Receptor - signal
Phototransforming – accumalation
Clathrochelates – tris-dioximates
Y= B, Ge, Sn, Sb,
Mn+= Fe2+, Co2+, Co1+, Ru2+
R = Hal, Ar, Alk, XAr, XAlk,
Z =F, Alk, Ph
Z
R
O
Y
NR
O
N
O
N
R
 accessibility by one or two-step synthesis;
Mn+
R
N
O
R N
O
Y
Z
The characteristic advantages of macrobicyclic
tris-dioximates:
N
O
R
stability in acidic and alkaline media;
metal ability to redox processes inside of the
ligand cavity;
the possibility of side and apical position
functionalization.
Design of new types of cavitands: conjugates
of clathrochelate and thiacalixarenes
Route a
Guest
O
O
S
S
SS
SS
HS
O
O
O
SH
SH
1,3-Alternate
Route b
S
O
S
O
SS
SS
Cl
Mn +
Cl
S S
S S
Mn +
O
O
SH
SH
Cone
Guest
S
O
Mn +
SS
SS
O
HS
Cl
O
Mn +
S
Cl
Mn +
Where we are going?
Synthesis calixarene/clathrochelate conjugates:
effect of methylene spacer length
S
F
O
N
B
O
N
Fe
N
O
N
O
B
O
O
N
SH
Cl
2+
N
(C H 2 )n
Cl
+
HS
(C H 2 )n
HS
(C H 2 )n
S
O
O
S
SH
O
O
(C H 2 )n
S
F
O
N
F
B
O
N
S
N
Fe2+
N
O
O (CH2 )n
O
N N
O
O
B
F
S (CH2 )n
S
S
O
S (CH2)n O
F
B
O O
N N
n=3, 4, 5
O
N
Fe 2+
S
O
S
(CH2 )n
S
N
O
N
O
B
F
N
O
Yield:
n=3: 0%
n=4: 58%
n=5: 2%
Synthesis calixarene/clathrochelate conjugates:
effect of methylene spacer length
S
F
B
O O
N N
Fe
N
N O
O B
F
O
HS
HS
O
O
S
S
S
S
O
S
O
N=3, Yield 20%
N
O
O
B
O
N
O
N
N
N
Cl
Fe
N
S
S
O
O
F
N
N
O
B
N=5, Yield 65%
B
O
O
S
N
O
F F
O
N
O
N
S
Fe
O
N
B
O
N
O
N
O
N
O
B
S
Cl
N
O
S
N
O
S
Fe
N
O
O
N
O
B
F
S
N
O
Noncovalent assembly of nanoaggregates
Extraction data
C
(Меn+)
= 0,1M, C(L) =10-4 - 2.5*10-3 M, С(Pic-) = 2.3*10-4 M
n
Cone-5
Cone-6
LogKex
E%
n
O
R
Ag+
Li+
LogKex
E%
0.8
3.3
61
0.7
4.1
79
1.9
8.4
100
1.1
6.1
99
Paco-5
0.6
2.0
22
1.5
8.4
68
Paco-6
1.0
4.5
81
1.6
8.2
100
Alternate -5
Alternate -6
0.6
2.0
16
2.0
9.9
98
0.8
3.3
53
1.9
9.8
100
S
O
R
O
S
O O O
S
O
O
R
O
Cone-5
-
-
84 / 0.18
Cone-6
-
143 / 0.19
153 / 0.08
Paco-5
-
-
134 / 0.16
Paco-6
-
-
131 / 0.17
Alternate -5
-
-
140 / 0.19
Alternate -6
-
-
141 / 0.23
R
R
R
OO
S
O
R
Paco
R
O
O
S
O
S
O
R
S
O
O
Nanoparticles size (nm) /Polydispersity
Ag+
O
O
S
OO
O
Cone
S
Li+
S
S
R
R
Free ligand
S
R
5
R=
6
R= N
N
O
O
1,3-Alternate
15
Nanoparticles size distribution of Ag
complex in CH2Cl2
3 hours
O
HN
O
S
S
S
O O
O
HN
OO
S
O
NH HN
Paco-7
+ Ag+
28 hours
16
17
SEM nanoparticles image of Ag(I) complex
in CH2Cl2
CH2 H2C
NH
HN
O
O
C
C
O
S
O
S
O
S
O
C OO C
NH
HN
H
C
CH2 2
1,3-alt - 10
S
The size of the aggregates formed thiacalix[4]arenes,
functionalized with hydrazide groups, with metal cations
Li+
+
Na
6a
6b
6c
1
1
2
2
0
0
K+
0
1
2
Cs+
3
2
1
3+
8
0
3
Fe3+
0
7
0
Ni2+
94
81
5
Cu2+
95
85
10
Co3+
91
16
1
Ag+
81
51
8
Pb
2+
67
10
2
Hg2+
0
87
36
Cd2+
90
17
4
Al
NH2
H2N
O
HN
H2N
NH
NH
O
S
O
H2N
S
O OO
S
O
NH
O
O
HN
HN
NH2
NH2
6a
O
S
S
S
O
NH
NH2
O
S
OO
HN
O
NH2 O
6b
S
S
O
NH HN
NH2
NH2
O
O
S
O
O
S
O
S
O
O
HN
HN
NH NH2
6c
2
100
80
60
40
20
0
6а
6б
6в
6в
6б
6а
Photo-switching of thiacalix[4]arene
derivative 1 containing azobenzene moieties
N
N
N
N
0.623
O
O
O
0.55
0.55
S
0.50
O
S
O
S
O
1
0.50
0.45
0.40
0.40
1
S
O
O
HN
HN
0.45
А
NH
NH
0.60
0.60
N
N
N
N
0.35
0.35
A 0.30
0.30
0.25
0.25
hv (365 nm)
2
0.20
0.20
0.15
0.15
N
N
0.10
0.10
N
N
0.05
0.05
0.002
NH
NH
220
220.0
240
240
260
260
280
280
300
300
320
320
340
340
360
360
380
380
nm
nm
400
400
420
420
440
440
460
460
480
480
500
500
520
520
540.0
540
O
O
S
UV spectra (5•10–6 mol L–1, 1cm cell) of p-tert butyl
thiacalix[4]arene in the trans (1) and cis (2) forms in
dichloromethane
O
S
O
HN
O
S
O
S
O
O
HN
N
N
N
N
2
Photo-switchable self-assembly of nanosized
aggregates
Ag+
S
H
N
N
N
N
N
N
Cu2+
S
S
O
synthezis
N
N
H
O
O
HO
N
O
O
O
O
N
H
N
N
Fe3+
aggregates
(61.1 nm)
aggregates
(188.9 nm)
aggregates
(125.7 nm)
S
hv (254 nm)
Ag+
S
N
H
N
N
N
N
O
HO
N
O
O
N
O
N
H
O
N
S
S
S
Fe3+
O
O
aggregates
(41.7 nm)
N
H
N
N
aggregates
(65.2 nm)
Model of photo-switchable self-assembly:
first step from the inanimate to living matter
Mn+
Mn+
Mn+
Mn+
M
Mn+
Mn+
Mn+
Mn+
n+
Mn+
Mn+
Mn+
Mn+
Mn+
Mn+
Mn+
Mn+
Mn+
Mn+
Mn+
Mn+
Mn+
Mn+
Mn+
Mn+
Mn+
Mn+
Mn+
Mn+
Mn+
Mn+
Mn+
Mn+
Mn+
Mn+
Mn+
Mn+
Mn+
Magnetic Resonance Imaging (MRI)
Commercial
contrast agents
Relaxivity R1p ~ 3000-5000 M-1s-1,
lgβ ~ 19-26
Main approaches to relaxivity enhancement:
- the induction of steric hindrance around the water binding site;
- the rise of the complex molecular mass due to aggregation.
Effect of macrocycle conformation
on Gd(III) relaxivity
R 1, M-1с -1
TC[4] Ac
paco
120000
конус
част.кон.
альт.
100000
80000
cone
60000
1,3-alt
40000
20000
0
0
0.1
0.2
0.3
0.4
0.5
C TC[4]Ac, мM
Acknowledgment
Academician A.I.Konovalov
Scientific team
in IOPC
Scientific team
in KFU
Dr. S.E.Solovieva
Dr. E.A.Popova
Dr. S.R.Kleshnina
Dr. M.N.Kozlova
Dr.A.A.Tuyftin
Prof. I.I.Stoikov
Dr.O.A.Mostovaya
A.Yu.Zhykov
E.A.Yushkova
E.A. Zaikov
Grants
Russian Foundation for Basic Research
Russian Academy of Sciences
Ministry of Education and Sciences RF
CRDF
Collaborators
Prof. Ya.Z.Voloshin
Prof. M.W.Hosseini
Prof. R.R.Amirov
Prof. A.R.Mustafina
Prof. G.A.Evtyugin
Dr. E.E.Stoikova
Dr. A.T.Gubaidullin