3rd Korea-US NanoForum, Seoul, Korea, April 3-4, 2006
Computer-Aided Molecular Design
of Nano Bio Sensors
Sihyun Ham
Nano/Bio Computational Chemistry lab.
Department of Chemistry, Sookmyung Women’s University,
Seoul, Korea
NANO / BIO
Computational Chemistry
Nano Bio Sensor
Analytes
Recognition unit
Transducer
Electronic signal
Optical signal
High Selectivity
High Sensitivity
What is the host?
• Structure-Function Relationship
What is the guest?
• Molecular Recognition
How they bind?
• Binding Mechanism
NANO / BIO
Computational Chemistry
Nano Bio Sensor
Analytes
Recognition unit
Li+, Na+, K+, Rb+, Cs+
Mg2+, Ca2+,Sr2+, Ba2+
Ag+, Zn2+, Pb2+,
NH4+ , amine, urea
F-,
Cl-,
NO3-,
Br-,
Transducer
OHHO
OHHO
O
OH HO
O
OH HO
NH2
O
O
S
I-,
OHHO
S
AcO-,
ClO4-,
H2PO4-, SO42-
OHHO
CF3
S
NO2
S
N
O
O
NH
amino acid
Polypeptide
Protein, DNA
drugs
glucose, cholesterol
O
O
N
N
N
O
O
HN
CH2
OH
NH
N
NO2
NO2
O2N
N
HN
NO2
NANO / BIO
Computational Chemistry
Nano Bio Sensor / Ca2+ Sensor
400
I - Io
100
OH
50
800
0
0
20
40
60
80
100
2+
free
2eq
4eq
6eq
8eq
10eq
50eq
100eq
500eq
800~1000eq
400
200
0
350
400
450
500
550
2+
Pb
[Pb ]/[2]
600
1000
OH
150
O
O
O
O
O
NH HN
800
2+
O
Ca
600
I - Io
200
1000
1000eq,1200eq
600eq
100eq
60eq
50eq
15eq
8eq
1eq
free
300
200
100
0
0
200 400 600 800 1000
2+
[Ca ]/[2]
400
200
600
0
350
400
450
500
550
600
NANO / BIO
Computational Chemistry
Nano Bio Sensor / Ca2+ Sensor
OH
OH
?
Pb2+
O
O
O
O
O
?
Ca2+
O
NH HN
Calix[4]arene
HomooxaCalix[4]arene
?Conformational preference
O
OH
HO
OH HO
OH
HO
OH HO
Thermodynamic stability
Electronic property
Binding sites
O
NANO / BIO
Computational Chemistry
Nano Bio Sensor / Ca2+ Sensor
Thermodynamic stability by Density functional theory
(B3LYP/6-311G**)
18.5
10.8
9.1
0.0
1.8
Relative Energy in kcal/mol
The first theoretical study
O
OH HO
OH HO
!Conformational preference
Thermodynamic stability
Electronic property
Binding sites
O
NANO / BIO
Computational Chemistry
Nano Bio Sensor / Ca2+ Sensor
OH
OH
O
O
O
O
O
H58 O57
H52
O51
O38
O
NH HN
O70
H89
H19
N88
O87 N18
Hydrogen bonding
N18–H19···O87
N88–H89···O70
O57–H58···O51
O51–H52···O38
distance (Å)
1.89
1.69
1.54
1.51
NANO / BIO
Computational Chemistry
Nano Bio Sensor / Ca2+ Sensor
OH
OH
O
O
O
O
O
H58 O57
H52
O51
O38
O
NH HN
O70
H89
H19
N88
O87 N18
HOMO
Hydrogen bonding
N18–H19···O87
N88–H89···O70
O57–H58···O51
O51–H52···O38
distance (Å)
1.89
1.69
1.54
1.51
LUMO
Py-Py* interaction -> excimer emission
S. Ham, J. Kim et al. Org. Lett. 2006, In Press.
NANO / BIO
Computational Chemistry
Nano Bio Sensor / Ca2+ Sensor
OH
OH
Pb2+
Pb2+
O
O
O
O
O
Ca2+
Ca2+
O
NH HN
Pb2+ complex : Py-Py* is not observed.
Ca2+ complex :Py-Py* -> excimer emission
Pb2+
Ca2+
Ca2+
HOMO
LUMO
HOMO
LUMO
NANO / BIO
S. Ham, J. Kim et al. Org. Lett. 2006, In Press.
Computational Chemistry
Nano Bio Sensor / NH4+ Sensor
Analytes
Recognition unit Transducer
Pb2+
O
+
K
N
H
O
NH4+
OH HO
Ca2+
OH HO
Cs+
O
O
N
H
Ag+
Pb2+
K+
NH4+
?
O
OH HO
OH HO
Ca2+
Cs
O
O
O
O
O
O
O
+
Ag+
NANO / BIO
Computational Chemistry
Selective Chemical Sensing / NH4+ Sensor
(a) cone
O
O
Ph
O
(c) 1,3-alternate
Ph
O
O OO
O
Ph
(b) C-1,2-alternate
PhO O
6.3
NH4+
0.0
3.4
PhPh
O
O
+
NH
4
O
O
O
OO
O
?
O O
Ph
Ph
Thermodynamic stability by Density functional theory (B3LYP/6-31G*)
NANO / BIO
Computational Chemistry
Selective Chemical Sensing / NH4+ Sensor
(a) cone
O
O
Ph
Ph
O
O
O OO
PhO O
NH4+
PhPh
O
O
+
NH
4
O
O
O
OO
O
Ph
(c) 1,3-alternate
Ph
?
O O
Ph
Relative Energy in kcal/mol
O
(b) C-1,2-alternate
6.3
4.2
0.0
3.4
7.7
Thermodynamic stability by Density functional theory (B3LYP/6-31G*)
0.0
NANO / BIO
Computational Chemistry
Computer-Aided Molecular Design of Nano Bio Sensors
Analytes
Recognition unit
Li+, Na+, K+, Rb+, Cs+
Mg2+, Ca2+,Sr2+, Ba2+
Ag+, Zn2+, Pb2+,
NH4+ , amine, urea
F-, Cl-, Br-, I-,
NO3-, AcO-, ClO4-,
H2PO4-, SO42amino acid
Polypeptide
Protein, DNA
drugs
glucose, cholesterol
Transducer
OHHO
OHHO
O
OH HO
OH
OH HO
NO2
O2N
O
S
OHHO
S
OHHO
NO2
S
N
S
N
NO2
NO2
CH2
O
O
NH
O
N
O
N
O
O
HN
O
NH
N
O
NH2
N
HN
CF3
• Structure-Function Relationship
• Molecular Recognition
• Binding Mechanism
NANO / BIO
Computational Chemistry