iscd2005

Computation of CD spectratools for quantitative stereochemical investigation

Gennaro Pescitelli

Università degli Studi di Pisa, Pisa, Italy

Consiglio Nazionale delle Ricerche- ICCOM, Pisa, Italy

[email protected]

Introduction

Extracting the information

from CD spectra

The sense of CD

• The achiral counterparts

UV-vis absorption, fluorescence, IR

detect certain molecular portions

(chromophores, fluorophores, bonds)

mainly responsible for interacting with radiation

• The chiral counterparts

Electronic CD, FDCD, CPL, VCD, ROA

specifically detect the reciprocal interaction

between “groups”, that is, are sensitive to their

relative spatial arrangement

� enantiomorphous shapes (abs. configuration)

� distance and orientations (conformation)

Types of approach

• Nature of system under investigation

• Molecular size

• Type and number of chromophoric groups

• Conformational freedom

• Kind of structural information sought

• Absolute configuration

• Solution conformation

• Degree of detail needed

Types of approach

• Empirical spectral correlations

• Semi-empirical rules

• Ketone octant rule

• Diene helicity rule

• Non-empirical straightforward methods

• Exciton chirality method

• Simplified calculations approaches

• Coupled-oscillator and matrix methods

• Full calculations of chiroptical properties

The need for calculations

• Providing a sound theoretical basis to immediate approaches

• Ketone octant rule

• Exciton chirality (ECCD)

• Substantiating everyday assignments

• Coping with complicate systems

(when no other approach is feasible)

• Looking for finer structural information

Levels of calculations

• Full optical activity prediction(one molecule, one calculation)

• Ab initio (CIS, TDDFT)

• Semi-empirical (PPP, CNDO, ZINDO-S/CI)

• Simplified methods

• Hypothesis: independent systems (ISA)

• Procedure:

1) “isolated” chromophore description

2) interaction of “isolated” transitions

Full calculations of optical activity

Electronic CD, plus examples

from VCD and optical rotation

Full calculations

• The quantum-mechanical foundation

• Rosenfeld’s equation

00 0= ⋅ii iR µ m

net µµµµ

net m

net charge

displacement

R < 0

Ψ0

Ψi

electric transition dipole

magnetic transition dipole

-200

-150

-100

-50

0

50

280 300 320 340 360

∆ε

λ (nm)

ε ( )iiR C d

ν

νν

ν

∆= ∫

CD band integral

Full calculations

• The electronic case

B. Le Guennic, W. Hieringer, A. Görling, J. Autschbach JPC A, 2005, 109, 4836S.G. Telfer, N. Tajima, R. Kuroda, M. Cantuel, C. Piguet Inorg. Chem. 2004, 43, 5302

Metal tris-phenantroline

(Average time: several hours – a few days)

• TDDFT

(Average time: a few minutes)

• ZINDO

Polyaromatics

Cr

Ln

Full calculations

• The vibrational case

(Average time: several hours)

T.B. Freedman, X. Cao, R.K. Dukor, L.A. Nafie Chirality 2003, 15, 743 (review)P.J. Stephens , F.J. Devlin Chirality 2000, 12, 172 (review)

Full calculations

• The [α] case

B. Mennucci, J. Tomasi, et al. J. Phys. Chem. A 2002, 106, 6102P.J. Stephens , D.M. McCann, J.R. Cheeseman, M.J. Frisch Chirality 2005, 17, S52

(1R)-β-pinene

(Average time: several hours)

12.915.9 15.2 Calc.

26.126.0 26.1 Exp. [α]D

CH3CNCH3OHacetone Solvent

29.9

26.6

C6H6

25.1

30.2

CCl4

18.4

26.2

C6H12

Calc.

Exp. [α]D

Solvent

• Practically limited to molecules

with [α] > 40-50 deg cm3 dm–1 g – 1

95% confidence

zone ofindeterminacy

Full calculations

• For absolute configurational assignment of rigid

or semi-rigid molecules, CD and (conveniently)

VCD calculations are usually more reliable than [α]

• When multiple conformations are possible,

absolute configuration prediction may become

exceedingly time-consuming (even for medium-

sized molecules)

• When conformational information is sought,

molecular size may be a limit and

computational time is a matter of concern

Full calculations

• A TDDFT calculation in practice

1) Generate geometries• Perform preliminary conformational searches

(MM or semi-empirical level)

• Compute DFT geometries and relative energies(usually done at B3LYP/6-31G(d))

• If possible, check against experimental data(NMR NOE’s and J’s)

2) Compute excited states and rotational strengths

for each conformer• Choose proper functional and large basis set

3) Average spectra(Boltzmann-weighted at room temperature)

4) Apply a bandshape(Gaussian bands with experiment-fit width σ)

2

( ) exp2 2

ii i

i

C vv R

νε ν

σ π σ

− ∆ = −

∑%%%%

Gaussian’03 (www.gaussian.com) - ADF (www.scm.com)Dalton (www.kjemi.uio.no/software/dalton/dalton.html)

• A TDDFT calculation in practiceSome computational issues

• Choice of the functional• Hybrid functionals perform better

(B3LYP, BHLYP, PBE0)

• Choice of the basis set• Sufficiently large basis set with

polarization (and diffuse) functions

(at least 6-31G+(d,p), better aug-cc-pVDZ)

• Rotational strength formulation

Full calculations

7288TZVP

20

4

1

Time

384aug-cc-pVDZ

2406-31++G(d,p)

1806-31G(d)

No. of bases

for C6H12O6

Basis set

1DVij

ij

R j i j iν

∝ ⋅ ×r� � �

�∇ ∇∇ ∇∇ ∇∇ ∇DL

ijR j i j i∝ ⋅ ×r r�� ∇∇∇∇

Dipole-length Dipole-velocity

• Ideally RDL≈ RDV

• Usually RDL is employed

C. Diedrich, S. Grimme J. Phys. Chem. 2003, 107, 2524 (review)J.C. Cramer “Essentials of Computational Chemistry”, Wiley, 2002

Applications

• Theoretical investigations of excited-states

and chiroptical properties

• Assignment of absolute configuration of

systems not amenable to simplified treatments

• Simple-chromophoric systems

not responding to sector rules

• Multi-chromophoric systems with

no clearcut exciton interaction

� Case 1: Aza-Diels-Alder adducts

• Inherently chiral chromophores

Case 1.

Absolute configuration assignment

of aza-Diels–Alder adducts

(S)-BINOL/ZnEt2 10%

(R)

N

O

P

O

EtO

EtO

Ar

O TMSMeO

N

Ar

P

O

EtO

EtO

O

Ar =

ee = 77% 18% 28%

• Aza-Diels–Alder reaction

• Imino dienophiles limited to N-aryl and N-tosyl

• Products employed as synthons for piperidine alkaloids

• No asymmetric synthesis reported

L. Di Bari et al. Synlett 2004, 4, 708

1. Absolute configuration ofAza-Diels–Alder products

0

2

4

-10

-5

0

5

10

15

200 250 300 350 400 450

104ε

∆ε

λ / nm

284 (-9.8)

235 (+10.7)

213 (+11.9)

283 (17,300)215 (14,000)

310 (-4.4,sh)

(a)

0

2

4

-10

-5

0

5

10

15

20

200 250 300 350 400 450

104ε

∆ε

λ / nm

313 (-8.2)

271 (+1.5)

229 (+11.0)

286 (17,500)

(b)

0

2

4

-20

-10

0

10

20

200 250 300 350 400 450

104ε

∆ε

λ / nm

300 (-9.6)

271 (+11.7)

234 (+92.0)

283 (16,800)

223 (83,600)

315 (-7.8)

/2

/5

222 (-61.0)

(c)

N

O

P

O

EtO

EtO

N

O

P

O

EtO

EtO

N

O

P

O

EtO

EtO

O

• Possible interpretations of CD spectra:

• Enone helicity and/or sector rules

• Arene/enone exciton coupling

• Full CD computations

N

O

H

(EtO)2PO

H

H

H

H

L. Di Bari et al. Chirality 2005, 17, 323


• Conformational analysis through molecular modeling

• Conformational analysis by NMR

• NOE’s and 3JH-H

N

O

H

(EtO)2PO

H

H

H

H3

2

6

5eq

5ax

J < 3 Hz

H

J = 7.3 Hz

NOE 2'

H

H

3'

4'

H2'

1'

H3'

4

1

N

OH

(EtO)2PO

HH

H

H

3

26

5eq

5ax

J < 3 Hz

H

J = 7.9 Hz

NOE2'

H8'NOE

H

HH

H

H

7'

6'

5'

4'

3'

N

OH

(EtO)2PO

HH

H

H

O

H

J < 3 Hz

J = 7.1 Hz

NOE

3

26

5eq

5ax

3'

H

H

4'

5'

cis-1 cis-2trans

Rel. E (kcal/mol): 0 +0.33 +0.39

1) Overall conformational search by MM

2) Selective scans by AM1

3) Final DFT optimizationB3LYP/6-31G(d)


• Helicity and sector rule for planar enones

0

2

4

6

8

10

-20

-15

-10

-5

0

5

10

15

200 250 300 350 400 450

104ε

∆ε

λ / nm

enone n→π*

NO RO

O

O

δ

λ

helicity rule sector rule

NO R

H

O

(S)

• Possible interferences:

• Enone non-planarity

• Aryl/enone conjugation

D.A. Lightner, J.E. Gurst ”Organic Conformational Analysis…”, Wiley, 2000


0

2

4

6

8

10

-20

-15

-10

-5

0

5

10

15

20

200 250 300 350 400 450

104ε

∆ε

λ / nm

enone π→π*

arene 1La

(R)

• Possible interferences:

• Coupling with other transitions

• Aryl/enone conjugation

• Enone/arene exciton coupling


• TDDFT calculations

i λi / nm fi Ri / 10–40

cgs Population(a)

Main character

1 297 0.0005 –8.2 71-75(0.64) n-π*C=O

2 244 0.27 –95.5 74-75(0.62) π-π*N·C:C·C:O

3 225 0.0008 –2.8 73-77(0.38) 72-76(0.36) π-π*Ph (Lb)

4 210 0.045 37.0 73-75(0.51)

5 202 0.007 9.4 73-75(0.43) 73-76(0.35)

6 199 0.002 –7.2 72-75(0.55) } π Ph-π*N·C:C·C:O

7 190 0.024 –2.2 74-76(0.56) 72-76(0.30)

8 181 0.09 –15.1 74-77(0.60) } πN·C:C·C:O-π*Ph

9 176 0.04 12.6 74-78(0.61) V-R(b)

10 174 0.57 –35.4 73-77(0.37) 72-76(0.35)

11 174 0.61 117.7 72-77(0.41) 73-76(0.32) } π-π*Ph (La+Lb)

12 163 0.02 2.3 74-79(0.50) V-R

-20

-10

0

10

20

30

-100

-50

0

50

100

150

150 200 250 300 350 400

∆ε R

75

74

73

72

71

76

77

HOMO

LUMO

BHLYP/TZVP//B3LYP/6-31G(d)

Ri rotational strength at λi

Gaussian bandcentered at λi

intensity ∝ Ri

energ

y


-20

-10

0

10

20

30

-100

-50

0

50

100

150

150 200 250 300 350 400

∆ε R

c1

-10

0

10

20

30

40

-50

0

50

100

150

200

∆ε R

t1

-10

0

10

20

30

-50

0

50

100

150

150 200 250 300 350 400

∆ε R

λ / nm

c2

-10

0

10

20

30

40

50

60

70

200 250 300 350 400 450

∆ε

λ / nm

Experimental

Calculated B3LYP

Calculated BHLYP

70 nm

35 nm

N (R)

O

P

O

EtO

EtO

Single confo

rmers

’com

pute

d spectra

Boltzmann-weigthed

average spectra at 298K

average

L. Di Bari et al. Chirality 2005, 17, 323


Simplified methods

for CD calculations

The Indipendent Systems Approximation,

DeVoe’s coupled-oscillator and matrix

methods

Simplified methods

• ISA approaches: key steps

1. Hypothesis on the dominant mechanism

• e.g., Coupled-dipole

2. Chromophore description

• From the literature

• Ad-hoc electronic structure calculations (NDO,TDDFT)

3. Solution structure elucidation

• NMR and other spectroscopies

• Geometry calculations (MM, semi-empirical, DFT)

4. Prediction of chromophores interactions

• Matrix-based calculations

Coupled-dipole

• Prerequisites:

• Non-chromophoric chiral skeleton

• Two or more “achiral” chromophores, with strong electric dipole allowed transitions

(e.g., π-π*), “close” in the space

• Magnetic dipole allowed transitions (e.g., n-π*)

do not interfere

• Chiral perturbation by non-chromophoric groups does not interfere

The theoretical basis of exciton chirality

∆ε

µµµµ1

µµµµ2

R12

CD of the“aggregate”

Chrom. 1Chrom. 2

Aggregate

Ener

gy

hν2hν1

Coupled-dipole

21 2 1,2

1,2 12 12 1 22 22 1

2ε ( ) exp V

hC

π ν ν ν νν

ν ν σ

− ∆ = ± − ⋅ ×

− R µ µ

[ ]1 212 1 2 1 12 2 12

312

3( )( )VR

µ µ= ⋅ − ⋅ ⋅e e e e e e

∝V12

V12

∝

Spectroscopic factor

Geometric factor

Negativechirality

Negativecouplet

λ

N. Harada and K. Nakanishi “Circular Dichroic Spectroscopy - Exciton Coupling in Organic Stereochemistry”, Oxford, 1983

DeVoe’s method

• The “aggregate” is composed of N damped oscillators,

described through their complex polarizability αi

• Each oscillator is perturbed by others (and the external field)

• The optical properties of the aggregate depend on the

interaction matrix Aij, i.e., on the reciprocal arrangement

between various oscillators

00

2

6909 ( )Im ( ) ( )

8ii

A

cI

N

ε νν ν

π να = = −

10

1

( ) ( ) ( )µ ν µ ν−

=

= α ⋅ −

∑N

i i ij ji

j

v Ge E

22

2,

24ε( ) Im ( )

3300

Aij i j ij

i j

NA

c

πν ν∆ = ×∑ e e R

[ ]

3

10

3( )( )

( )

i j i ij j ijij

ij

ij ij ij i

GR

A G vδ−

⋅ − ⋅ ⋅=

= + α

e e e e e e

C. Rosini, M. Zandomeneghi, P. Salvadori Tetrahedron Asymm. 1993, 4, 545C. Rosini, G. Egidio, S. Superchi Chirality 2005, 16, 422 (review)

• The framework

• A calculation in practice

• Input: electric transition dipolesgeometry and parameters

• Position (molecular structure)

• Direction (known or calculated)

• Frequency, magnitude, bandwidth(from UV-vis spectra of isolated chromophores)

• Output: absorption and CD spectra

DeVoe’s method

(Time: a few seconds)

[Fortran program available on request]

Matrix method

• Tinoco’s sum-of-terms expression

'

C

C

C

P

ab

ab ab

C

C

Ca

Ca C

b

b

R

V

V

V

∝ ⋅

+ ⋅

+ ⋅

+ ⋅ ×

∑∑∑∑

µ

µ

µ

µ

m

µR

m

m

(a) Inherently chiral chromophore (e.g., helicene)

(b) Perturbed achiral chromophore (e.g., saturated ketones)

(c) Two chromophores (one provides µ, one m)

(d) Two µ-allowed chromophores (exciton coupling)

• Matrix formulation

1 1 1 2 1

1 2

21 2 2

1 2

11 1

1 2

22

2

2 21

0

0

m m

mm m

m m

mm m

E V V V

V E V

V V E V

V V E

µ µ µ µ µ

µ µ

µµ µ µ µ

µ µ

=

H

(b) (d) (c)

(b) (c)

(d) (c) (b)

(c) (b) isolated transitions frequencies

interaction potential betweentransition charge distributions

1 212

r s

rsr s

VR

ρ ρ=∑∑

I. Tinoco Adv. Phys. Chem. 1962, 4, 113P.M. Bayley, E.B. Nielsen, J.A. Schellman JPC 1969, 73, 228

Matrix method

• Features:

• Treats all “mechanisms” of optical activity,

(in particular, m-allowed transitions)

except intrinsic chirality

• Conjugation/resonance/charge transfer

phenomena between chromophores

must be excluded

• Can account for degenerate states

Matrix method

• A calculation in practice

• Input (in addition to DeVoe’s):

• Magnetic transition moments

(position, direction, intensity)

• Transition charge densities(localized monopoles ρi)

• Static charge densities

(placed on atoms)

J. Sandström in ”Circular Dichroism: Principles…”, Wiley, 2000, ch. 16

(Time: a few seconds)

Applications

• Substantiating simplified approaches

� Case 2: dihydrofurocoumarins

• Absolute configuration assignment

of multi-chromophoric compounds

� Case 3: Sandström’s spiro compounds

• Conformational analysis of complex systems

� Case 4: tetra-binaphthyl porphyrins

� Case 5: biopolymers, e.g. proteins

Case 2.

Absolute configuration assignment

of dihydrofurocoumarins

2. Absolute configuration of

Dihydrofurocoumarins

• The furocoumarines

• Biologically-active compounds with a wide range of activities

• No general non-empirical method for the

absolute configurational assignment

• Case study: a styril-substituted angelicin

• Racemate synthesis and prep-HPLC resolution

• Absolute configuration: Exciton chirality method?

OO O

R4R2

R3

R1

8

1011

O O

I

AcO+

dioxane/H2O

Pd(dba)2/dppe

Ag2CO3 OO O

Ph

OO O

G. Pescitelli, N. Berova, T.L. Xiao, R.V. Rozhkov, R.C. Larock, D.W. Armstrong Org. Biomol. Chem. 2003, 1, 186

• Conformational analysis through molecular modeling

1) Overall conformational search by MM

2) Selective scans by DFT

3) Final DFT optimization

Absolute minimumB3LYP/6-31G(d)

• Conformational analysis by NMR

• One set of signals

• NOE and 3JH-H analysis confirm modelling results

syn

anti

anti

NOE’sGeometry fromKarplus’ curve



H

O

H

O

H

Me

O

H

H

HH

H

H

H

HH

H

8

10

119

C8-C10 rotation

5-membered ring conformation

• UV/CD spectrum assignment

OO OMe

-25

-20

-15

-10

-5

0

5

10

0

1

2

3

4

5

6

7

240 260 280 300 320 340 360

∆ε

104

ε

λ (nm)

319 nm

∆ε +7.7

253 nm

∆ε -8.0

252 nm, ε 23,000

321 nm, ε 12,700

CD

UV



OO O

coumarin

π-π* band

π-π* 1La

(K) band

(Polarization from excited-statescalculations, ZINDO and TDDFT)



G. Pescitelli, N. Berova, T.L. Xiao, R.V. Rozhkov, R.C. Larock, D.W. Armstrong Org. Biomol. Chem. 2003, 1, 186

(S)

-10

-5

0

5

10

240 280 320 360 400

Experimental Calculated

∆ε

λ (nm)

• Exciton chirality and DeVoe calculations

Positive chirality

Positive CD couplet

(S) Absolute configuration

• Broadening the scope

• Extension to 9-alkenyldihydrofurocoumarins



(S)

(R)

O

Me

OO

R3*

R1

R2

H

O

Me

OO

R3*

R2

H

K. Tanaka, G. Pescitelli, L. Di Bari, T.L. Xiao, K. Nakanishi,D.W. Armstrong, N. Berova Org. Biomol. Chem. 2004, 2, 48

O

Me

OO

MeMe

I

O

Me

OO

MeMe

Pd(OAc)2, PPh3

Ag2CO3

DMF, 80 oC

**

HH

RuCl2

PhHC PCy3

CH2Cl2 ∆O

Me

OO

Me*

O

Me

OO

Me*

Me

NN

H-20

-15

-10

-5

0

5

10

15

Experimental

Calculated

∆ε

-15

-10

-5

0

5

10

15

240 280 320 360 400

Experimental

Calculated

∆ε

λ (nm)

Case 3.

Absolute configuration of spiro-

compounds with mirror-

image CD spectra


Sandström’s spiro-compounds

• Two synthetic spiro compounds having:

• Same configuration

• Same chromophores

• Apparently similar

geometry

• Mirror-image CD spectra

L. Ripa, A. Hallberg, J. Sandström JACS 1997, 119, 5701

-80

-60

-40

-20

0

20

40

200 220 240 260 280

∆ε

λ (nm)

N

HO

N

HO



• UV/CD spectrum assignment

-80

-60

-40

-20

0

20

40

200 220 240 260 280

∆ε

λ (nm)

1B

1La

1LbK

benzenoid

π-π*1Bb,

1Lb

1Ba,1La

formyl vinyl amineπ-π* (K band)

N

HO

N

HO



• Conformational analysis (MM2 calculations)

+0.6 kcal/mol

benzene viewpoint formyl vinyl amine viewpoint

N

HO

N

HO



1Bb,1Lb

1Ba,1La

carbonyl n-π*

5 µ-allowed + 1 m-allowed

6x6 interaction matrix

• Matrix-method calculations

N

HO

N

HO

N

HO

K

L. Ripa, A. Hallberg, J. Sandström JACS 1997, 119, 5701

experimental

experimental

calculated

calculated

Case 4.

Conformational investigation of

asymmetric catalysts:

tetrabinaphthyl porphyrins

• High-simmetry 1,1’-binaphthyl/porphyrin atropisomeric catalysts• Fe and Mn complexes used in the

enantioselective alkene epoxidation

• Investigation of solution conformation towarda rationale of observed activity and selectivity

4. Conformational study of


G. Reginato, L. DI Bari, R. Guilard, P. Salvadori Eur. J. Org. Chem. 2000, 1165

X

N

N

N NX

X

Fe

X

X

N

N

N NX

X

X

Fe

X = OMe

C4 symmetry

αααα isomer

"4α"

D2 symmetry

αβαβ isomer

"αβ"

N

N

N

N N

N

N

N



• Effective 4-fold symmetry

• Little quantitative information obtained

L. Di Bari, G. Pescitelli, G. Reginato, P. Salvadori Chirality 2001, 13, 548

• NMR spectra and NOE’s

X

N

N

N NX

X

X

ψθ

2×4 = 8 main degrees of conformational freedom

HNN

NNH

bNp

bNp

bNp

H8

HP

HP'

CH3O

8'H

no NOEobserved

Observed NOE4444αααα twice as ααααββββ

OCH3 ring current shift: 4444αααα twice as ααααββββ

θθθθ > 70°

• Semi-empirical PM3 geometry optimizations



4α αβ

Several mimina found withcorrelated 70 < θθθθ ≈ ψ ψ ψ ψ < 120°

One sharp absolute minimumhaving θθθθ = 90°, ψψψψ = 90°

θ

ψ

θ

ψ



• Experimental UV-vis/CD

0

0.5

1

1.5

2

2.5

3

3.5

4

200 250 300 350 400 450 500 550 600

10

5 ε

-400

-200

0

200

400

600

200 250 300 350 400 450 500 550 600

∆ε

λ (nm)

4α αβ

HNN

NNH1Bb

Soret

1Lb

1La

Q

10 dipoles and 44 couplinginteractions overall!

HN

N

N

NHbNp

bNp

bNp

degenerateinter-bNpcoupling

degenerateintra-bNp coupling

non-degenerateNp/Porp coupling



• Calculated UV-vis/CD spectra 60

90120

ψ = 60

θ =

6090120

200 250 300 350 400 450 500 550 600

ψ = 120

θ =

λ (nm)

6090120

0

1 105

2 105

3 105

4 105

5 105

ψ = 90

θ =

ε

6090120

ψ = 60 θ =

6090120

-3000

-2000

-1000

0

1000

2000

3000

ψ = 90 θ =

∆ε

6090120

200 250 300 350 400 450 500 550 600

ψ = 120 θ =

λ (nm)

N

N

N N

X

X

ψψψψθθθθ

bNpbNp

Geometry sampling (MMX):

scan of θθθθ and ψψψψ between

60°-120° by 15° step

(25 overall structures)

4α



• Best-fitting spectraobtained with θθθθ ≈ 75°, ψψψψ ≈ 75°

0

0.5

1

1.5

2

2.5

3

10

5 ε

4α

Experimental

Calculated

-400

-200

0

200

400

200 250 300 350 400 450 500 550 600

∆ ε

λ (nm)

/ 4

L. Di Bari, G. Pescitelli, G. Reginato, P. Salvadori Chirality 2001, 13, 548

Case 5.

Conformational and theoretical

studies on proteins

• CD of polypeptides and proteins

• Extremely sensitive to secondary structure

α-helix

β-sheet

β-turn

unorderedhemoglobin

lysozyme

elastase

• Very rich in chromophores

• Liable to multichromophoric ISA calculations

N. Sreerama, R.W. Woody in ”Circular Dichroism: Principles and Applications”, Wiley, 2000, chapter 21 (review)

5. Protein CD calculations

• Matrix method

• Amide chromophores (µµµµ- and m-allowed transitions)

N

O

H

π-π* (NV1) 190 nm

π-π* (NV2) 140 nm

n-π*220 nm

R.W. Woody, N. Sreerama JCP 1999, 111, 2844

See also: K.A. Bode, J. Applequist JACS 1998, 120, 10938

Hemoglobin Elastase

experimental calculated



• Matrix method

• Side-chain chromophores

Bovine pancreatic trypsin inhibitor

N. Sreerama et al. Biochemistry 1999, 38, 10814

1Ba (190 nm)1La (230 nm)

1Bb (190 nm)1Lb (280 nm)

OH

exper.

amide only

including sidechains

amide only

including sidechains

experimental

HNN

NNH

Soret (≈420 nm)Q (≈550 nm)

• Matrix method

• Extrinsic chromophores


Hemoglobin(tetramer)

M.C. Hsu, R.W. Woody JACS 1971, 93, 3516

experimental

calculated

Conclusions

Contact: [email protected]

• Two basic questions:

• What kind of information is needed?

• How complex (large, flexible) is the system?

• TDDFT may be the answer…

• for assigning absolute configuration of “small”,

“rigid” molecules (but consider VCD, as well!)

• when using other methods is questionable

• ISA-based approaches may be the answer…

• if some assumptions are met

• for complex and/or flexible systems

whose chromophores are well-characterized

• for CD-based conformational studies

A rational approach to quantitative CD calculations

iscd2005

Documents

vcd calculations

calculations approaches

reviewfull calculations

computation of cd spectratools

devlin chirality

frisch chirality

nafie chirality

pineneaverage time