Post on 30-Dec-2015
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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
Lviv, 6-10 September 2010
I.S.Antipin, S.E.Solovieva, I.I.Stoikov, A.I.Konovalov
Moscow
Kazan
Novosibirsk
St.Petersbourg
V International symposium “Design and Synthesis of Supramolecular Architectures”
12-16 October 2009
VI International symposium “Design and Synthesis of Supramolecular Architectures”
September 18-23, 2011
http://iopc.ru/butlerov/Index-e.html
Basic principle of supramolecular chemistry
Jonathan Swift
Macrocycles– molecular platform for multipoint interactions realization and multivalent ligands design.
Macrocyclic platforms
O
OH
OO
OH
OH
OHOH
O
OH
OOH
OHOH
R
OH
X n
HOOH HO
OH
OHHOOH
HO
R RR
R
Calixarenes
CalyxCalyx CPK-CPK-ModelModel
XXX X
H H H H
SSS S
XXX X
H H H H
X=O, S, NH
OOO O
H H H H
Calix[4]arenes
SSS S
OOO O
H H H H
The characteristic advantages of calix[4]arenes for the constructing of receptors are followed: 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;
1997 – S.Miyano et al
Thiacalix[4]arene
O OOO
H HH H
OH
HO
H
O
OH
OO
H H
HO
H
O
OO
H H
HO
H
O
Cone Partial Cone
V≈10A3
1,3-Alternate 1,2-Alternate
Background of Calixarene Chemistry
Main Problem:
Stereo and Regio Selective Functionalization of Lower and Upper Rim
SSS
S
OHOHOH OH
Upper Rim
Lower Rim
Mono, Di, Tri and Tetra Substituted Derivatives
O OOO
R RR R
OR
RO
R
O
OR
OO
R R
RO
R
O
Cone Partial Cone 1,3-Alternate 1,2-Alternate
OO
R R
RO
R
O
1. Covalent assembly: towards nanosized molecules
2. Noncovalent assembly: towards “soft” nanosystems
2
n + nFunctionsReceptor - signalPhototransforming – accumalation
hν “guestquenching
Outline
Y= B, Ge, Sn, Sb, Mn+= Fe2+, Co2+, Co1+, Ru2+
R = Hal, Ar, Alk, XAr, XAlk, Z =F, Alk, PhYO
OO
NN
NR
R N
OY
OO
N N
R
R
R
R
Mn+
Z
Z
Clathrochelates – tris-dioximates
The characteristic advantages of macrobicyclic tris-dioximates:
accessibility by one or two-step synthesis;
stability in acidic and alkaline media;
metal ability to redox processes inside of the ligand cavity;
the possibility of side and apical position functionalization.
Mn + Cl
Cl
SS
SH O S
SHO S
HS
HS
O
OS
S
S O S
SO S
S
S
O
OMn +Mn +
Guest
1,3-Alternate
Mn + Cl
Cl
SH SH
OOSSSS
S
S OO
S
S S
S
Mn +
Guest
Design of new types of cavitands: conjugates of clathrochelate and thiacalixarenes
Route b
Route a
Cone
Where we are going?
S
O
O
O
O
S
S
S
(C H 2)nSH
(C H 2)n
(C H 2)n
(C H 2)n
HS
HS
SH
F
Cl
BOO
O
N N N
N
OB
OO
N N
Fe 2+
F
Cl+
S
O
O
O
O
S
S
S
B OO
O
NNN
N
OBOO
NN
Fe
F
F
(CH2)nS
(CH2)n
(CH2)n
(CH2)n
S
SS
BOO
O
N N N
N
OBO O
N NFe
F
F
n=3, 4, 5
2+ 2+Yield:n=3: 0%n=4: 58%n=5: 2%
Synthesis calixarene/clathrochelate conjugates:effect of methylene spacer length
Synthesis calixarene/clathrochelate conjugates:effect of methylene spacer length
N=3, Yield 20%
S
O
O
O
O
S
S
S S
S
HS
HS
B OO
ONNN
NO
BOONN
Fe
F
F
B O
O
O
NN
N
N
O
B
OO
NN
F e
S
O
O
O
O
S
S
S
S
S
S
SBO
O
O
NN
N
N
O
B
OO
N N
Fe F
F
F
BO
O
O
NN
N
N
O
B
OO
N N
F e
F
C l
C l
N=5, Yield 65%
Nanoparticles size (nm) /Polydispersity
Free ligand Li+ Ag+
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
Extraction data C (Меn+) = 0,1M, C(L) =10-4 - 2.5*10-3 M, С(Pic-) = 2.3*10-4 M
Li+ Ag+
n LogKex E% n LogKex E%
Cone-5 0.8 3.3 61 0.7 4.1 79
Cone-6 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 0.6 2.0 16 2.0 9.9 98
Alternate -60.8 3.3 53 1.9 9.8 100
15
R
O
OO
O
RRR
S SOOO O
S S
RR O
O
O
O
R
R
SO
S SO OOS
RR
O O
OO
O
RR
S SO
O
OS
S
R= N O
R= N
5
6
Cone Paco
1,3-Alternate
Noncovalent assembly of nanoaggregates
16
3 hours
28 hours+ Ag+HNHN O
O
O
O
HN
NH
SO
S SO OO
S
Nanoparticles size distribution of Ag complex in CH2Cl2
Paco-7
C OHN
C
S SO
O
OSS
O
CONH
C OHN NH
O
CH2 H2C
CH2H2C
SEM nanoparticles image of Ag(I) complex in CH2Cl2
17
1,3-alt - 10
The size of the aggregates formed thiacalix[4]arenes, functionalized with hydrazide groups, with metal cations
HN
O
OO
O
NHHN
NH
S SOOO O
S S
H2NNH2 NH2
NH2
6a
HNHNO
O
O
O
HN
NH
SO
S SO OO
S
NH2
NH2 NH2NH2
6b
NHNH
O O
OO
O
HNHN
S SO
O
OS
S
H2N H2N
NH2NH2
6c
220.0 240 260 280 300 320 340 360 380 400 420 440 460 480 500 520 540.0
0.002
0.05
0.10
0.15
0.20
0.25
0.30
0.35
0.40
0.45
0.50
0.55
0.60
0.623
nm
A
220 240 260 280 300 320 340 360 380 400 420 440 460 480 500 520 540
nm
0.60
0.55
0.50
0.45
0.40
0.35
0.30
0.25
0.20
0.15
0.10
0.05
А
1
2
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
NHNH
O O
OO
O
HN
S SO
O
OS
S
HN
N
N
N
NN
N
N
N
NHNH
O O
OO
O
HN
S SO
O
OS
S
HN
N
N
N
NN
N
N
N
hv (365 nm)
1
2
Photo-switching of thiacalix[4]arene derivative 1 containing azobenzene moieties
NH
NH
O
O
O
O
O
HN
S
S
OO
O
S
S
HN
N
NN
N
N
N N
N
NH
NH
O
O
O
O
O
HN
S
S
OO
O
S
S
HN
N NNN
NNNN
Ag+
Cu2+
Fe3+
Ag+
Fe3+
aggregates(61.1 nm)
aggregates(188.9 nm)
aggregates(125.7 nm)
aggregates(41.7 nm)
aggregates(65.2 nm)
synt
hezi
s
hv (254 nm)
Photo-switchable self-assembly of nanosized aggregates
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+
Mn+
Mn+
Mn+
Mn+
Mn+
Mn+ Mn+
Mn+
Mn+
hν (2
54 n
m)
Model of photo-switchable self-assembly:first step from the inanimate to living matter
Magnetic Resonance Imaging (MRI)
Relaxivity R1p ~ 3000-5000 M-1s-1,
lgβ ~ 19-26
Commercial contrast agents
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
0
20000
40000
60000
80000
100000
120000
0 0.1 0.2 0.3 0.4 0.5
C TC[4]Ac, мM
R 1, M-1с-1 конус
част.кон.альт.
cone
paco
1,3-alt
TC[4] Ac
Acknowledgment
Scientific team in KFU
Prof. I.I.StoikovDr.O.A.Mostovaya A.Yu.ZhykovE.A.Yushkova E.A. Zaikov
GrantsRussian Foundation for Basic ResearchRussian Academy of Sciences Ministry of Education and Sciences RF CRDF
Academician A.I.Konovalov
Collaborators
Prof. Ya.Z.VoloshinProf. M.W.HosseiniProf. R.R.AmirovProf. A.R.MustafinaProf. G.A.EvtyuginDr. E.E.StoikovaDr. A.T.Gubaidullin
Scientific team in IOPC
Dr. S.E.SolovievaDr. E.A.PopovaDr. S.R.KleshninaDr. M.N.KozlovaDr.A.A.Tuyftin