Dissecting Interactions in Solution Scott L. Cockroft UKQSAR Autumn - - PowerPoint PPT Presentation

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Dissecting Interactions in Solution Scott L. Cockroft UKQSAR Autumn - - PowerPoint PPT Presentation

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Dissecting Interactions in Solution Scott L. Cockroft UKQSAR Autumn meeting, 29 th September 2017 Understanding & exploiting conformational change Unfolded Folded equilibrium K fold + measurement I. K. Mati & S. L. Cockroft. Chem.

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SLIDE 1

Dissecting Interactions in Solution

Scott L. Cockroft

UKQSAR Autumn meeting, 29th September 2017

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SLIDE 2

Folded

+

Unfolded

Kfold

measurement

equilibrium

Understanding & exploiting conformational change

  • I. K. Mati & S. L. Cockroft. Chem. Soc. Rev. 39, 4195-05 (2010)
slide-3
SLIDE 3

Interaction Energy, DG = DH – TDS

electrostatic induction dispersion repulsion desolvation van der Waals interactions translational rotational vibrational

Dissecting interactions

configurational states

DG = –RT lnK

  • bservable

behaviour

slide-4
SLIDE 4

Interaction Energy, DG = DH – TDS

electrostatic induction dispersion repulsion desolvation van der Waals interactions translational rotational vibrational

Dissecting interactions

configurational states

DG = –RT lnK

  • bservable

behaviour

slide-5
SLIDE 5
  • 30
  • 20
  • 10

OR bifurcated binding?

CD3CN CDCl3

Linear binding - polarisability of H-bond chain?

DGcomplex / kJ mol–1

Molecular Balances – geometric control

slide-6
SLIDE 6

Folded

+

Unfolded

Kfold

ΔGfold= – RT lnKfold measurement

BALANCE equilibrium

Molecular torsion balances

  • I. K. Mati & S. L. Cockroft. Chem. Soc. Rev. 39, 4195-05 (2010)

Kfold

slide-7
SLIDE 7
  • I. K. Mati & S. L. Cockroft. Chem. Soc. Rev. 39, 4195-05 (2010)

1.00 1.69

ΔGfold= – RT lnKfold

+

Unfolded

Kfold

Folded measurement

equilibrium

Molecular torsion balances

Kfold

slide-8
SLIDE 8
slide-9
SLIDE 9
  • 10
  • 8
  • 6
  • 4
  • 2

2 4

  • 30
  • 20
  • 10

10

DGbalance / kJ mol–1 DEbalance / kJ mol–1

R2 = 0.99

Computational vs. exp. conformational energies

B3LYP/6-311G*

  • N. D. Whiteley, J. J. Brown, S. L. Cockroft, Angew. Chem. Int. Ed., 56, 7658-62 (2017)
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SLIDE 10

Computations of longer chains

DEcomplex DEbalance

  • 25
  • 20
  • 15
  • 10
  • 5
  • 55
  • 50
  • 45
  • 40
  • 35

/ kJ mol–1 / kJ mol–1

B3LYP/6-311G*

  • N. D. Whiteley, J. J. Brown, S. L. Cockroft, Angew. Chem. Int. Ed., 56, 7658-62 (2017)

to cc-pVDZ

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SLIDE 11
  • 25
  • 20
  • 15
  • 10
  • 5

4 × a b c d e f h i g j a b c d e f i g j h 1 × 2 × 3 × 4 × 2 × 3 × k l m H-Bonds in chain

∆E / kJ mol–1

External phenol at end of chain = ideal H-bond geometry

B3LYP/6-311G* to cc-pVDZ

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SLIDE 12

Methanol chain

  • 80
  • 60
  • 40
  • 20

Interaction E / kJ mol–1

Computations of longer chains

Amide Chain

  • 50
  • 40
  • 30
  • 20
  • 10

Interaction E / kJ mol–1

Methanol Chain

  • N. D. Whiteley, J. J. Brown, S. L. Cockroft, Angew. Chem. Int. Ed., 56, 7658-62 (2017)

B3LYP/6-311G* to cc-pVDZ

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SLIDE 13

H-bond chains Conclusion

  • Doubling of interaction energy on going from one to two

H-bonds (i.e. inductive polarisation is significant)

  • Limited range = through-space field effects plus

inductive polarisation being rapidly maximised at the end of a chain.

  • Short range effect (2 to 3 H-bonds = little additional

change)

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SLIDE 14

Interaction Energy, DG = DH – TDS

electrostatic induction dispersion repulsion desolvation van der Waals interactions translational rotational vibrational

Dissecting interactions

configurational states

DG = –RT lnK

  • bservable

behaviour

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SLIDE 15

methanol iodine

0 kJ mol–1 –200 kJ mol–1

s-hole interactions?

perfluoro- selenophene halogen bonding chalcogen bonding e.g. O→S, O→Se, S→Se, O→Te etc electrostatic? dispersion?

  • rbital

delocalisation? group 16 elements hydrogen bonding d+ d- d+ d- d+ d-

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SLIDE 16

Interaction Energy, DG = DH – TDS

electrostatic induction dispersion repulsion desolvation van der Waals interactions translational rotational vibrational

Dissecting interactions

configurational states

DG = –RT lnK

  • bservable

behaviour

  • rbital

delocalisation?

slide-17
SLIDE 17

Electrostatics? van der Waals dispersion? Orbital delocalisation? Interaction

The origin of chalcogen bonding interactions

e-

O→S O→Se S→S

slide-18
SLIDE 18
  • 10
  • 8
  • 6
  • 4
  • 2

Chloroform-d DG (kJ/mol) EDG → EWG

  • 6
  • 4
  • 2

2 4

DG (kJ/mol)

Chloroform-d X = Me X = H X = Cl X = COOMe X = COMe X = COH X = Me X = H X = COH X = H X =Me X = H X = Cl

The origin of chalcogen bonding interactions

Chloroform-d Chloroform-d

DGEXP / kJ mol–1 DGEXP / kJ mol–1

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SLIDE 19

The origin of chalcogen bonding interactions

DGEXP / kJ mol–1 DGEXP / kJ mol–1

EDG → EWG

  • D. J. Pascoe, K. B. Ling, S. L. Cockroft, J. Am. Chem. Soc., accepted, (2017)
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SLIDE 20

Electrostatics van der Waals dispersion? Orbital delocalisation

The origin of chalcogen bonding interactions

e-

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SLIDE 21

R² = 0.94

  • 8
  • 7
  • 6
  • 5
  • 4
  • 3
  • 2
  • 1

1 2

  • 10
  • 5

5 ΔGEXP(CDCl3)/ kJmol–1 ΔECALC/kJ mol–1 R² = 0.88

  • 8
  • 7
  • 6
  • 5
  • 4
  • 3
  • 2
  • 1

1 2

  • 10
  • 5

5 ΔGEXP(CDCl3)/ kJmol–1 ΔECALC/kJ mol–1

NO DISPERSION B3LYP/6-311G* DISPERSION “CORRECTED” M06-2X/6-311G*

DGchloroform / kJ mol–1

The origin of chalcogen bonding interactions

Also, measured DG values were very similar in CS2 = high bulk polarizability MeOH = low bulk polarizability

DGchloroform / kJ mol–1

  • D. J. Pascoe, K. B. Ling, S. L. Cockroft, J. Am. Chem. Soc., accepted, (2017)
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SLIDE 22

Electrostatics van der Waals dispersion? Orbital delocalisation

The origin of chalcogen bonding interactions

e-

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SLIDE 23

Bond lengthening seen B3LYP/6-311G*

O lone pair (n) σ* (C–S)

n→σ* orbital delocalization / interactions

Natural Bond Orbital (NBO) analysis

  • D. J. Pascoe, K. B. Ling, S. L. Cockroft, J. Am. Chem. Soc., accepted, (2017)
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SLIDE 24
  • 11
  • 10
  • 9
  • 8
  • 7
  • 6
  • 5
  • 11
  • 10
  • 9
  • 8
  • 7
  • 6

Orbital energy - closed conf. / eV Orbital energy - open conf. / eV

The origin of chalcogen bonding interactions

slide-25
SLIDE 25
  • 8
  • 6
  • 4
  • 2

2

  • 8.2
  • 8.0
  • 7.8
  • 7.6
  • 7.4
  • 7.2

Energy of n→σ* orbital / eV

X Y

  • 8
  • 6
  • 4
  • 2

2

  • 11.4
  • 11.2
  • 11.0
  • 10.8
  • 10.6
  • 10.4

Energy of res.-delocalised orbital / eV

  • X

Y

R² = 0.99

n→σ*

S-C

n→σ*

H-C

and

  • rbitals

Resonance-delocalised orbitals

n→σ* orbital delocalization / interactions

DGchloroform / kJ mol–1 DGchloroform / kJ mol–1

  • D. J. Pascoe, K. B. Ling, S. L. Cockroft, J. Am. Chem. Soc., accepted, (2017)
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SLIDE 26

Electrostatics van der Waals dispersion? Orbital delocalisation

The origin of chalcogen bonding interactions

slide-27
SLIDE 27

Interaction Energy, DG = DH – TDS

electrostatic induction dispersion repulsion desolvation van der Waals interactions translational rotational vibrational

Dissecting interactions

configurational states

DG = –RT lnK

  • bservable

behaviour

What about entropic effects on H-bonding?

  • rbital

delocalisation

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SLIDE 28

The limit of intramolecular H-bonding

  • T. A. Hubbard, S. L. Cockroft, J. Am. Chem. Soc., 138, 15114-7 (2016)
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SLIDE 29

The limit of intramolecular H-bonding

  • T. A. Hubbard, S. L. Cockroft, J. Am. Chem. Soc., 138, 15114-7 (2016)
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SLIDE 30

Reference

K′inter

D E

Kinter

C A B

The limit of intramolecular H-bonding

Kobs = Kinter/(1 + Kintra)

  • T. A. Hubbard, S. L. Cockroft, J. Am. Chem. Soc., 138, 15114-7 (2016)
  • C. A. Hunter, H. L. Anderson, Angew. Chem.
  • Int. Ed. 48, 7488-99 (2009)
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SLIDE 31
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SLIDE 32
  • Entropic penalty of 5-6 kJ mol-1 per rotor!

The limit of intramolecular H-bonding

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SLIDE 33

The limit of intramolecular H-bonding

  • Surprising, almost binary behaviour.
  • Large penalty of 5-6 kJ mol-1 per rotor!

Overall summary

  • Folding molecules/atropisomers are excellent tools

for dissecting non-covalent interactions and solvent effects OR solvent effects great for understanding conformational preferences!

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SLIDE 34

Nick D. Whiteley John Brazier James Brown Cath Adam Lina Mati Lixu Yang Tom Hubbard Dominic Pascoe

And… finally…

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SLIDE 35
slide-36
SLIDE 36
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SLIDE 37