3rd Korea-US NanoForum, Seoul, Korea, April 3-4, 2006

Computer-Aided Molecular Design of Nano Bio Sensors

Nano/Bio Computational Chemistry lab.

Sihyun Ham

Department of Chemistry, Sookmyung Womens University, Seoul, Korea

NANO / BIO Computational Chemistry

Nano Bio Sensor

Analytes Recognition unit Transducer

Electronic signal

Optical signal

High Selectivity
What is the host? What is the guest? How they bind?

High Sensitivity
Structure-Function Relationship Molecular Recognition Binding Mechanism
NANO / BIO Computational Chemistry

Nano Bio Sensor

Analytes Recognition unit Transducer

Li+, Na+, K+, Rb+, Cs+ Mg2+, Ca2+,Sr2+, Ba2+ Ag+, Zn2+, Pb2+, NH4+ , amine, urea F-, NO3-, Cl-, Br-, I-, ClO4-, H2PO4-, SO42AcO-,
S

OHHO OHHO

O OH HO OH HO O

NH2

S OHHO OHHO S
O O O

CF3
NO2

N
O

NH

N
O

amino acid Polypeptide Protein, DNA drugs glucose, cholesterol

HN

CH2
OH O2N NO2

NO2

NH N

N HN

NO2

NANO / BIO Computational Chemistry

Nano Bio Sensor / Ca2+ Sensor

200

400

I - Io

100 50

OH
0 20 40 60 80 100

800

[Pb ]/[2]
600
free 2eq 4eq 6eq 8eq 10eq 50eq 100eq 500eq 800~1000eq

2+

Pb

2+

O O O O NH HN

800

Ca

2+
600

1000eq,1200eq 600eq 100eq 60eq 50eq 15eq 8eq 1eq free

I - Io

1000

150

OH

1000

300 200 100 0 0 200 400 600 800 1000 2+

[Ca ]/[2]

400

400

200

200

0 350

400

450

500

550

600

0 350

400

450

500

550

600

NANO / BIO Computational Chemistry

Nano Bio Sensor / Ca2+ Sensor

OH OH

?
Calix[4]arene

Pb2+

O O O

Ca2+

NH HN

HomooxaCalix[4]arene
O

? Conformational preference
Thermodynamic stability Electronic property Binding sites

OH OH

HO HO

OH HO OH HO O

NANO / BIO Computational Chemistry

Nano Bio Sensor / Ca2+ Sensor

Thermodynamic stability by Density functional theory (B3LYP/6-311G**)

18.5 9.1 0.0 1.8 10.8

Relative Energy in kcal/mol

The first theoretical study

O OH HO OH HO O
NANO / BIO Computational Chemistry

!Conformational preference
Thermodynamic stability Electronic property Binding sites

Nano Bio Sensor / Ca2+ Sensor

OH OH O O O O O
H58 O57 H52 O51 O38

NH HN

O70

H89 H19 N88 O87 N18

Hydrogen bonding N18H19O87 N88H89O70 O57H58O51 O51H52O38

distance () 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

NH HN

O70

H89 H19 N88 O87 N18

Hydrogen bonding N18H19O87 N88H89O70 O57H58O51 O51H52O38

distance () 1.89 1.69 1.54 1.51

HOMO

LUMO
NANO / BIO Computational Chemistry

Py-Py* interaction -> excimer emission

S. Ham, J. Kim et al. Org. Lett. 2006, In Press.

Nano Bio Sensor / Ca2+ Sensor

OH OH

Pb2+

Pb2+

O O O

Ca2+
O

Ca2+

NH HN

Pb2+ complex : Py-Py* is not observed.

Pb2+

Ca2+ complex :Py-Py* -> excimer emission

Ca2+

Ca2+

HOMO

LUMO

HOMO

LUMO
NANO / BIO Computational Chemistry

S. Ham, J. Kim et al. Org. Lett. 2006, In Press.

Nano Bio Sensor / NH4+ Sensor

Analytes
Pb2+

Recognition unit Transducer

O

NH4+

N H

Ca2+

OH HO OH HO
O N H

Cs+
Ag+

Pb2+

K+

NH4+

O OH HO OH HO
O

O O

O O

Ca2+

Cs

Ag+

NANO / BIO Computational Chemistry

Selective Chemical Sensing / NH4+ Sensor

(a) cone (b) C-1,2-alternate (c) 1,3-alternate

O O O Ph

Ph O O O OO PhO O

Ph

6.3

NH4+

0.0

3.4

PhPh O O NH4+ O O O OO O Ph O O

Ph
NANO / BIO Computational Chemistry

Thermodynamic stability by Density functional theory (B3LYP/6-31G*)

Selective Chemical Sensing / NH4+ Sensor

(a) cone (b) C-1,2-alternate (c) 1,3-alternate

O O O Ph

Ph O O PhO O O OO

Ph

Relative Energy in kcal/mol

6.3

NH4+

0.0

3.4

PhPh O O NH4+ O O O OO O Ph O O

Ph

4.2

7.7 0.0
NANO / BIO Computational Chemistry

Thermodynamic stability by Density functional theory (B3LYP/6-31G*)

Computer-Aided Molecular Design of Nano Bio Sensors

Analytes 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
S

Recognition unit

Transducer

OHHO OHHO

O OH HO OH HO O

OH O2N NO2

S OHHO OHHO S
O O O

NO2

NO2

NH

N
O O O

HN

NO2 O
NH N N HN

CH2 NH2

CF3

Structure-Function Relationship Molecular Recognition Binding Mechanism

NANO / BIO Computational Chemistry