Application of Hard-Soft Acid-Base (HSAB) Theory to Reactions - - PowerPoint PPT Presentation

Application of Hard-Soft Acid-Base (HSAB) Theory to Reactions between Amino Acids and Quinone Methides

Samuel Samuel Edeh Edeh

• Faculty mentor

Faculty mentor – – Dr. Robert Dyer

• Dr. Robert Dyer

2004 Student Research Conference 2004 Student Research Conference Truman State University, Kirksville MO Truman State University, Kirksville MO

Introduction: Introduction:

• Bronsted

Bronsted Acid/Base Concept Acid/Base Concept – – Acid donates H Acid donates H+

+

– – Base accepts H Base accepts H+

+

• Lewis Acid/Base Concept

Lewis Acid/Base Concept – – Acid accepts electrons (e Acid accepts electrons (e-

• )

) – – Base donates electrons (e Base donates electrons (e-

• )

)

Introduction: Introduction:

• Hard

Hard-

• Soft Acid

Soft Acid-

• Base (HSAB) Theory

Base (HSAB) Theory – – Ralph G. Pearson (1963) Ralph G. Pearson (1963) – – “Hard acids prefer to associate with hard “Hard acids prefer to associate with hard bases, and soft acids prefer to associate bases, and soft acids prefer to associate with soft bases.” with soft bases.”

Background: Background:

• Molecular

Molecular orbitals

• rbitals

– – Highest Occupied Molecular Orbital, HOMO Highest Occupied Molecular Orbital, HOMO – – Lowest Unoccupied Molecular Orbital, LUMO Lowest Unoccupied Molecular Orbital, LUMO

En+2 E1 E2 E3 En En+1

↑↓ ↑↓ ↑↓ ↑↓

HOMO LUMO

Unocccupied Molecular Orbitals (+) Occcupied Molecular Orbitals (-)

Background: Background:

• Electron affinity,

Electron affinity, A A – – Energy change when atom accepts an Energy change when atom accepts an electron electron – – Energy of LUMO ( Energy of LUMO (-

• )

)

En+2

HOMO LUMO

En+1 E1 E2 E3

↑↓ ↑↓ ↑↓ ↑↓

En

Background: Background:

• Ionization energy,

Ionization energy, I I – – Energy required to remove an electron Energy required to remove an electron from an atom from an atom – – Energy of HOMO (+) Energy of HOMO (+)

En+2

HOMO LUMO

En+1 E1 E2 E3

↑↓ ↑↓ ↑↓ ↑↓

En

Background: Background:

• Absolute hardness,

Absolute hardness, η η

2 A I − = η 2 LUMO HOMO− = η

http://web.utk.edu/~cebarnes/C430/lecs/weblec6.pdf

LUMO HOMO 2 − = η

Background: Background:

• Absolute softness,

Absolute softness, σ σ

• Reactivity

Reactivity – – “Hard acids prefer to associate with hard “Hard acids prefer to associate with hard bases, and soft acids prefer to associate bases, and soft acids prefer to associate with soft bases.” with soft bases.”

η σ 1 =

Method: Method:

• Calculate

Calculate – – LUMO and HOMO energies LUMO and HOMO energies – – η η

• Predict reactivity

Predict reactivity (Based on (Based on η η) )

• Computer program Gaussian

Computer program Gaussian

Experiment: Experiment:

O C(CH3)3 (H3C)3C

H2N CH C CH2 OH O CH2 CH2 CH2 NH2

+

tert tert-

• ButylMethyl

ButylMethyl Quinone Quinone Methide Methide ( (t t-

• BMQM)

Arginine Arginine BMQM)

Computation: Computation:

• tert

tert-

• ButylMethyl

ButylMethyl Quinone Quinone Methide Methide ( (t t-

• BMQM)

BMQM) – – Electrophile Electrophile (accepts electrons into LUMO) (accepts electrons into LUMO) – – HF 3 HF 3-

• 21G*

21G* – – HF 6 HF 6-

• 311G

311G

• Amino acids

Amino acids – – Nucleophiles Nucleophiles (donate electrons from HOMO) (donate electrons from HOMO) – – HF 3 HF 3-

• 21G*

21G* – – HF 6 HF 6-

• 311G

311G

Geometry optimization Geometry optimization HF 3-21G*

HOMO LUMO |2η| t-BMQM

• 0.32053

0.05119 0.37172 Arginine

• 0.34805

0.19350 0.54155 Isoleucine

• 0.36465

0.18352 0.54817 Tryptophan

• 0.28232

0.13472 0.41704 Cysteine

• 0.36193

0.12653 0.48846 Lysine

• 0.36129

0.18477 0.54606 Tyrosine

• 0.31102

0.13958 0.45060

Geometry optimization Geometry optimization HF 6-311G

HOMO LUMO |2η| t-BMQM

• 0.3185

0.04561 0.36414 Arginine

• 0.3309

0.13512 0.46603 Isoleucine

• 0.3744

0.14242 0.51681 Tryptophan

• 0.2866

0.11992 0.40649 Cysteine

• 0.3659

0.12568 0.49154 Lysine

• 0.3714

0.14950 0.52090 Tyrosine

• 0.3164

0.12339 0.43977

Result analysis: Result analysis:

Relative rates for reaction between Relative rates for reaction between t-BMQM and amino acids k (M-1s-1)† Cys 3320 Tyr 45.0 Arg 17.2 Tryp 14.1 Ile 7.90 HF 3-21G* HF 6-11G Tryp Tryp Tyr Tyr Cys Arg Arg Cys Ile Ile

† J. Org. Chem. 1997, 62, 1820-1825

Why is data discrepant with Why is data discrepant with published relativities? published relativities?

• Used fairly simple Gaussian computation

Used fairly simple Gaussian computation

• Ignored nature of reaction system

Ignored nature of reaction system

• pH

pH

• Temperature

Temperature

• Solvent

Solvent

• Optimization level

Optimization level

Why study Why study quinone quinone methides methides? ?

• Good guy:

Good guy:

• Melanization

Melanization

• Sclerotization

Sclerotization

• Lignin formation

Lignin formation

• Bad guy:

Bad guy:

• Cytotoxicity

Cytotoxicity

Acknowledgments Acknowledgments Thanks to Thanks to – –Dr. Robert G. Dyer

• Dr. Robert G. Dyer

– –You for listening You for listening Questions? Questions?

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