Download Application of Hard-Soft Acid-Base

Application of Hard-Soft Acid-Base
(HSAB) Theory to Reactions between
Amino Acids and Quinone Methides
Samuel Edeh
- Faculty mentor – Dr. Robert Dyer
2004 Student Research Conference
Truman State University, Kirksville MO
Introduction:
„
„
Bronsted Acid/Base Concept
– Acid donates H+
– Base accepts H+
Lewis Acid/Base Concept
– Acid accepts electrons (e-)
– Base donates electrons (e-)
Introduction:
„
Hard-Soft Acid-Base (HSAB) Theory
– Ralph G. Pearson (1963)
– “Hard acids prefer to associate with hard
bases, and soft acids prefer to associate
with soft bases.”
Background:
„
Molecular orbitals
– Highest Occupied Molecular Orbital, HOMO
– Lowest Unoccupied Molecular Orbital, LUMO
(+)
(-)
Unocccupied
Molecular
Orbitals
Occcupied
Molecular
Orbitals
En+2
En+1
En
↑↓
E3
↑↓
↑↓
↑↓
E2
E1
LUMO
HOMO
Background:
„
Electron affinity, A
– Energy change when atom accepts an
electron
– Energy of LUMO (-)
En+2
En+1
En
↑↓
E3
↑↓
↑↓
↑↓
E2
E1
LUMO
HOMO
Background:
„
Ionization energy, I
– Energy required to remove an electron
from an atom
– Energy of HOMO (+)
En+2
En+1
En
↑↓
E3
↑↓
↑↓
↑↓
E2
E1
LUMO
HOMO
Background:
„
Absolute hardness, η
I−A
η=
2
η=
HOMO− LUMO
2
http://web.utk.edu/~cebarnes/C430/lecs/weblec6.pdf
2η = HOMO − LUMO
Background:
„
Absolute softness, σ
σ= 1
η
„
Reactivity
– “Hard acids prefer to associate with hard
bases, and soft acids prefer to associate
with soft bases.”
Method:
„
„
„
Calculate
– LUMO and HOMO energies
– η
Predict reactivity
(Based on η)
Computer program Gaussian
Experiment:
O
O
(H3C)3C
H2N
C(CH3)3
CH
C
OH
CH2
+
CH2
CH2
CH2
NH2
tert-ButylMethyl
Quinone Methide
(t-BMQM)
Arginine
Computation:
„
„
tert-ButylMethyl Quinone Methide (t-BMQM)
– Electrophile (accepts electrons into LUMO)
– HF 3-21G*
– HF 6-311G
Amino acids
– Nucleophiles (donate electrons from HOMO)
– HF 3-21G*
– HF 6-311G
Geometry optimization
HF 3-21G*
HOMO
LUMO
|2η|
t-BMQM
-0.32053
0.05119 0.37172
Arginine
Isoleucine
Tryptophan
Cysteine
Lysine
Tyrosine
-0.34805
-0.36465
-0.28232
-0.36193
-0.36129
-0.31102
0.19350
0.18352
0.13472
0.12653
0.18477
0.13958
0.54155
0.54817
0.41704
0.48846
0.54606
0.45060
Geometry optimization
HF 6-311G
HOMO
LUMO
|2η|
t-BMQM
-0.3185
0.04561 0.36414
Arginine
Isoleucine
Tryptophan
Cysteine
Lysine
Tyrosine
-0.3309
-0.3744
-0.2866
-0.3659
-0.3714
-0.3164
0.13512
0.14242
0.11992
0.12568
0.14950
0.12339
0.46603
0.51681
0.40649
0.49154
0.52090
0.43977
Result analysis:
Relative rates for reaction between t-BMQM and
amino acids
k (M-1s-1)†
Cys
Tyr
Arg
Tryp
Ile
†
3320
45.0
17.2
14.1
7.90
HF 3-21G*
Tryp
Tyr
Cys
Arg
Ile
J. Org. Chem. 1997, 62, 1820-1825
HF 6-11G
Tryp
Tyr
Arg
Cys
Ile
Why is data discrepant with
published relativities?
„
„
„
Used fairly simple Gaussian computation
Ignored nature of reaction system
-pH
-Temperature
-Solvent
Optimization level
Why study quinone methides?
„
„
Good guy:
-Melanization
-Sclerotization
-Lignin formation
Bad guy:
-Cytotoxicity
Acknowledgments
Thanks to
– Dr. Robert G. Dyer
– You for listening
Questions?
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