AGC Redox Active Ligands - Princeton Universitychemlabs.princeton.edu/.../6/AGC_Redox_Active_Ligands.pdf · 2014. 2. 4. · "Redox-active, or 'noninnocent,' ligands have more energetically

Redox-Active Ligands

MacMillan Group MeetingAndrew Capacci

2/4/14

Coordination Chemistry and Metal-Ligand Interactions

! The coordination of metal complexes have been described in the classical terms of Werner complexes

Jørgensen, C. K. Coord. Chem. Rev., 1966, 1, 164.Chirik, P. J. Inorg. Chem., 2011, 50, 9737.

FeNH3

CoNH3

NH3

H3N

H3N

NH3

FeCp2

3+

[Co(NH3)6]Cl3

PtCl

H3N

H3N

Cl

PtCl2(NH3)2

! Considered "innocent" ligands as the metal oxidation state is easily predicted

NH3

CoNH3

NH3

H3N

H3N

NH3

3+

[Co(NH3)6]Cl3

NH3 = L type

overall charge = +3

Co(III)

Fe

FeCp2

PtCl

H3N

H3N

Cl

PtCl2(NH3)2

Cp = X type

overall charge = 0

Fe(II)

Cl = X type

overall charge = 0

Pt(II)


! The coordination of metal complexes have been described in the classical terms of Werner complexes

Jørgensen, C. K. Coord. Chem. Rev., 1966, 1, 164.Chirik, P. J. Inorg. Chem., 2011, 50, 9737.

FeNH3

CoNH3

NH3

H3NH3N

NH3

FeCp2

3+

[Co(NH3)6]Cl3

PtCl

H3NH3N

Cl

PtCl2(NH3)2

! Considered "innocent" ligands as the metal oxidation state is easily predicted

! Non-innocent ligands are classified as having experimentally determined oxidation state differ from prediction

N

NN

N

FeIV

SR

O

Fe(IV), ligand radical cation

Which oxidation state doesthe iron center in Compound I

actually exist in?

Me

Me–O2C

–O2CMe

N

NN

N

FeV

SR

OMe

Me–O2C

–O2CMe

Fe(V), neutral ligand

Non-Innocent vs. Redox-Active Ligands

! What's the difference between "noninnocent" and "redox active" ligands?

Chirik, P. J., Wieghardt, K. Science, 2010, 327, 794.Chirik, P. J. Inorg. Chem., 2011, 50, 9737.

"Oftentimes, the two descriptions 'redox-active' and 'noninnocent' ligands are used interchangeablyin the literature. However, care must be used when using the latter because clearly defined physicaloxidation states have often been established for a case where ambivalence has been implied."

-Chirik (2011)


N

NN

N

FeIV

SR

O



actually exist in?

Me

Me–O2C

–O2CMe

N

NN

N

FeV

SR

OMe

Me–O2C

–O2CMe


"Redox-active, or 'noninnocent,' ligands have more energetically accessible levels that allow redoxreactions to change their charge state."

-Chirik, Weighardt (2010)





-Chirik (2011)


N

NN

N

FeIV

SR

O



actually exist in?

Me

Me–O2C

–O2CMe

N

NN

N

FeV

SR

OMe

Me–O2C

–O2CMe




Fe(IV) state





-Chirik (2011)




Milstein cat. (0.1 mol%)

toluene, ! N

RuEt2N PtBu2

CO

H

OH

R'H2N

R"

O

NH

R'R"

–2 H2

! Non-redox-active cooperative ligation is interesting but beyond the scope of this discussion


! Early discovery of noninnocent ligands: metal dithiolene complexes (1960s)

Eisenberg, R., Gray, H. B. Inorg. Chem., 2011, 50, 9741.

! Dithiolene complexes were examined for their spectroscopic and redox properties

SM

S

S

SR

R

R

R

R = Ph, CN, CF3

M = Ni, Cu, Co, Pd, Pt

The conventional assignmentof V(S2C2Ph2)3 would require aV(VI) metal center! (3p5 valency)

S

SS

V

S

SS

PhPh

Ph

Ph Ph

Ph

SNi

S

S

SPh

Ph

Ph

Ph SNi

S

S

SPh

Ph

Ph

Ph

Ni(II), d8 Ni(IV), d6

SNi

S

S

SPh

Ph

Ph

Ph

Ni(0), d10


! Early discovery of noninnocent ligands: metal dithiolene complexes (1960s)

Eisenberg, R., Gray, H. B. Inorg. Chem., 2011, 50, 9741.

! Dithiolene complexes have applications in catalysis: Mo oxotransferases

SM

S

S

SR

R

R

R

R = Ph, CN, CF3

M = Ni, Cu, Co, Pd, Pt

The conventional assignmentof V(S2C2Ph2)3 would require aV(VI) metal center! (3p5 valency)

S

SS

V

S

SS

PhPh

Ph

Ph Ph

Ph

MoSS S

S

OSerine

RR

RRMe

SMe

OMe

SMe

Advantages of Redox-Active Ligands

! Confering noble reactivity to non-noble metals

Blackmore, K. J., Ziller, J. W., Heyduk, A. F. Inorg. Chem., 2005, 44, 5559.Haneline, M. R., Heyduk, A. F. J. Am. Chem. Soc., 2006, 128, 8410.

! Reductive elimination from a Zr(IV) center is also possible with redox-active ligands

O

tBuNO

Zr

O

OtBuN

tBu

tBu

tBu

tBu

Cl

tBuNO

Zr

Cl

OtBuN

tBu

tBu

tBu

tBu

Cl2

Ph

tBuNO

Zr

Ph

OtBuN

tBu

tBu

tBu

tBu

O

tBuNO

Zr

O

OtBuN

tBu

tBu

tBu

tBu

2–

[Cp2Fe]PF6 (2 equiv.)

THF, -78 °C then-78 °C to rt

Oxidative additionwith a d0 metal complex

reductive eliminationfrom Zr(IV)

Advantages of Redox-Active Ligands

! Generation of novel reactivity:

Prier, C. K., Rankic, D. A., MacMillan, D. W. C. Chem. Rev., 2013, 113, 5322.

452 nm

t2g

eg

t2g

eg

!* (bpy)

t2g

eg

!* (bpy)

t2g

eg

!* (bpy)strong oxidant

Ru(bpy)33+

Ru(bpy)3+

E1/2 = +.79 V

strong reductant

E1/2 = –.83 V

Ru(bpy)32+ *Ru(bpy)32+

N

NN

N

N

NRu

2+

N

NN

N

N

NRu

2+*

Classes of Redox-Active Ligands

M+nLSpectator Ligand

Lyaskovskyy, V., de Bruin, B. ACS Catal., 2012, 2, 270.Luca, O. R., Crabtree, R. H. Chem. Soc. Rev., 2013, 42, 1440.


M+nL

M+nL

-e–

S

M+nL

S

M+(n+2)L-2

S

Modification of metal electronicsvia ligand modification

Electron transfer to ligand

Spectator Ligand



M+nL

M+nL

-e–

S

M+nL

S

M+(n+2)L-2

S



Spectator Ligand Actor Ligand



M+nL

M+nL M+nL

M+(n+1)L

SX

SX

S

S•

M+nL

S

-e–

S

M+nL

S

M+(n+2)L-2

S

Modification of metal electronicsvia ligand modification Ligand assisted substrate activation

Redox-active substrate complexElectron transfer to ligand



M+nL

M+(n+1)L

SX

SX

S

S•

M+nL

S

S

M+nL

S

M+(n+2)L-2

S

Ligand assisted substrate activation


Actor Ligand


M+nL

M+nL

-e–


Spectator Ligand


Ligand Controlled Modification of Catalytic Activity

! Early studies by Wrighton in rhodium catalyzed processes

Lorkovic, I. M., Duff, R. R., Wrighton, M. S. J. Am. Chem. Soc., 1995, 117, 3617.

CoII

P

P

Rh

PhPh

PhPh

Solv. CoIII

P

P

Rh

PhPh

PhPh

Solv.

2++

–e–

+e–

! Reduced catalyst complex is 16 times more reactive towards alkene hydrogenation

! Oxidized catalyst complex was found to be more reactive for ketone hydrosilylation


! Use of redox-active ligands as switches in Lewis acid mediated polymerizations

! An efficient redox switch would be desirable for thecontrolled synthesis of block copolymers

Ti NNOO

tBu tBu

OiPr

OiPrFeIIFeII

Gregson, C. K. A., Gibson, V. C., Long, N. J. Marshall, E. L., Oxford, P. J., White, A. J. P. J. Am. Chem. Soc., 2006, 128, 7410.

Ti NNOO

tBu tBu

OiPr

OiPrFeIIIFeIII

–2e–

+2e–

Active catalyst Inactive catalyst

O

O

O

O

Me

Me

HO

O

OHMe n

Ti-salen cat.


! Use of redox-active ligands as switches in Lewis acid mediated polymerizations

! Rate of polymerization decreases with increasedLewis acidity of the metal comlex

Ti NNOO

tBu tBu

OiPr

OiPrFeIIFeII

Gregson, C. K. A., Gibson, V. C., Long, N. J. Marshall, E. L., Oxford, P. J., White, A. J. P. J. Am. Chem. Soc., 2006, 128, 7410.

Ti NNOO

tBu tBu

OiPr

OiPrFeIIIFeIII

–2e–

+2e–

Active catalyst Inactive catalyst

O

O

O

O

Me

Me

HO

O

OHMe n

Ti-salen cat.

M+nL

M+(n+1)L

SX

SX

S

S•

M+nL

S

S

M+nL

S

M+(n+2)L-2

S



Actor Ligand


M+nL

M+nL

-e–


Spectator Ligand


M+nL M+nL

M+(n+1)L

SX

SX

S

S•

M+nL

S

-e–


Redox-active substrate complex

Actor Ligand


M+nL

S

M+nL

S

M+(n+2)L-2

S


Spectator Ligand


Redox Active Bis(imino)-Pyridine Ligand with Iron(II)

! Brookhart developed bulky pyridine diimine ligands for use in polymerization

! In 2006, involvement of the PDI ligand upon two-electron reduction of the iron complex was established

Small, B. L., Brookhart, M., Bennett, A. M. A. J. Am. Chem. Soc., 1998, 120, 4049.Bart, S. C., Chlopek, K., Bill, E., Bouwkamp, M. W., Lobkovsky, E., Neese, F., Wieghardt, K., Chirik, P. J. J. Am. Chem. Soc., 2006, 128, 13901.

NFe

N

N

Me

Me

Ar

Ar

XX

Ar = 2,6-(iPr)2-C6H3

nMAO

NFeII

N

N

Me

Me

Ar

Ar

XX

NFe0

N

N

Me

Me

Ar

Ar

N2N2

NFeI

N

N

Me

Me

Ar

Ar

N2N2

NFeII

N

N

Me

Me

Ar

Ar

N2N2

2 e–

major resonanceform


! Brookhart developed bulky pyridine diimine ligands for use in polymerization

! In 2006, involvement of the PDI ligand upon two-electron reduction of the iron complex was established

Small, B. L., Brookhart, M., Bennett, A. M. A. J. Am. Chem. Soc., 1998, 120, 4049.Bart, S. C., Chlopek, K., Bill, E., Bouwkamp, M. W., Lobkovsky, E., Neese, F., Wieghardt, K., Chirik, P. J. J. Am. Chem. Soc., 2006, 128, 13901.

NFe

N

N

Me

Me

Ar

Ar

XX

Ar = 2,6-(iPr)2-C6H3

nMAO

NFeII

N

N

Me

Me

Ar

Ar

N2N2

major resonanceform

NFeII

N

N

Me

Me

Ar

Ar

N

NMe2

vs.


! Chirik has developed bis(imino)-pyridine iron(II) dinitrogen complexes with unique reactivity

Bouwkamp, M. W., Bowman, A. C., Lobkovsky, E., Chirik, P. J. J. Am. Chem. Soc., 2006, 128, 13340.

NFe

N

N

Me

Me

Ar

Ar

N2N2Ar = 2,6-(iPr)2-C6H3

E E

H

H

10 mol%

E =

CH2

NBn

NtBu

C(CO2Et)2

Time (min) Conv. (%) TOF (h-1)

300 92 1.8

26 90 21

< 5 > 95 > 240

141 > 95 4

benzene, 23 °C



Bouwkamp, M. W., Bowman, A. C., Lobkovsky, E., Chirik, P. J. J. Am. Chem. Soc., 2006, 128, 13340.

NFeII

N

N

Me

Me

Ar

Ar E

NFeII

N

N

Me

Me

Ar

ArE

H

H

NFe

N

N

Me

Me

Ar

Ar

N2N2Ar = 2,6-(iPr)2-C6H3

E E

H

H

10 mol%

! PDI ligand acts as an electron sink to enable metallocene formation and reductive elimination

benzene, 23 °C



Sylvester, K. T., Chirik, P. J. J. Am. Chem. Soc., 2009, 131, 8772.Bouwkamp, M. W., Bowman, A. C., Lobkovsky, E., Chirik, P. J. J. Am. Chem. Soc., 2006, 128, 13340.

! Reductive enyne cyclizations are also possible via similar mechanism

NTs NTsMe

Me

Me

79% yield, 6.7 TOF

NFe

N

N

Me

Me

Ar

Ar

N2N2Ar = 2,6-(iPr)2-C6H3

E E

H

H

10 mol%

NFe

N

N

Me

Me

Ar

Ar

N2N2Ar = 2,6-(iPr)2-C6H3

10 mol%

H2 (4 atm), benzene, 23 °C

benzene, 23 °C


! Terminal alkene hydrosilylation for use in industrial applications

Tondreau, A. M., Atienza, C. C. H., Weller, K. J., Nye, S. A., Lewis, K. M., Delis, J. G. P., Chirik, P. J. Science, 2012, 335, 6068, 567.

NFe

N

N

Me

Me

Ar

Ar

N2N2

Me MeR3Si

! One of the largest-scale applications of homogeneous catalysis

! Used to produce a range of silicone-based surfactants, fluids, molding products,release coatings, and pressure-sensitive adhesives

! Current production relies upon the use of Nobel metal catalysts (Pt, Pd, Ru, and Rh)

! Estimated that industry consumed 5.6 metric tons of Pt in 2007

R3Si–H, neat, 23 °C




NFe

N

N

Me

Me

Ar

Ar

N2N2

Me MeR3Si

Catalyst

1

mol %

0.05

0.04

0.03

Silane

(TMSO)2MeSiH

(EtO)3SiH

Et3SiH

Time Yield (GC)

15 min

15 min

1 hr

> 98%

96%

trace

0.02

0.02

Et3SiH

Et3SiH

15 min

45 min

9%

> 98%

1, Ar = 2,6-(iPr)2-C6H3

NFe

N

N

Me

Me

Ar

ArN2N2 2

Ar = 2,6-(Et)2-C6H3, 2Ar = 2,6-(Me)2-C6H3, 3

R3SiH, [Fe]

2

3

1

1

0.004 (TMSO)2MeSiH 15 min > 98%3 25,000 turnovers

neat, 23 °C




C5H11

Et3Si

NFe

N

N

Me

Me

Ar

ArN2N2 2

Ar = 2,6-(Me)2-C6H3

NFeII

N

N

Me

Me

Ar

Ar

C5H11

NFeII

N

N

Me

Me

Ar

Ar

H11C5

NFeII

N

N

Me

Me

Ar

Ar

H

C5H11

Et3Si

NFeII

N

N

Me

Me

Ar

Ar

Et3Si

C5H11

AlkeneHydrosilylation

Et3Si H

Negishi-type Coupling Using Cobalt(III)

! Breakthrough use of Cobalt(III) for alkyl halide oxidative addition and reductive elimination

! Oxidative addition results in formation of semiquinonate complex

Smith, A. L., Hardcastle, K. I., Soper, J. D. J. Am. Chem. Soc., 2010, 132, 14358.

CoN

NO

O

t-Bu

t-Bu

t-Bu

t-BuPh

Ph

CoN

NO

O

t-Bu

t-Bu

t-Bu

t-BuPh

PhEt

ZnBr

Et

CoIII(Et)(apPh)2[CoIII(apPh)2]–

[CoIII(apPh)2]–

EtBr

10-15% yield



! Oxidative addition highly responsive to sterics


CoN

NO

O

t-Bu

t-Bu

t-Bu

t-BuPh

Ph

CoN

NO

O

t-Bu

t-Bu

t-Bu

t-BuPh

PhEt

ZnBr

Et


[CoIII(apPh)2]–

EtBr

Alkyl electrophile:

Reaction Time:

CH3I, CH3OTf

< 30 sec

EtI EtBr

<1 min 1 hr

i-PrI

3 hrs

BnBr

24 hrs

BnCl

> 48 hrs

! Oxidative addition likely occurs through an SN2 type mechanism

10-15% yield



! Treatment with organozinc reagents induces reductive elimination in low yield


CoN

NO

O

t-Bu

t-Bu

t-Bu

t-BuPh

Ph

CoN

NO

O

t-Bu

t-Bu

t-Bu

t-BuPh

PhEt

ZnBr

Et


[CoIII(apPh)2]–

EtBr

CoIII(Et)(apPh)2remaining Ph–Et yield

11%

15%

15%

15%

PhZnBr(equiv.)

2

4

6

10

20%

7%

3%

2%

10-15% yield

M+nL M+nL

M+(n+1)L

SX

SX

S

S•

M+nL

S

-e–



Actor Ligand


M+nL

S

M+nL

S

M+(n+2)L-2

S


Spectator Ligand



M+nL

M+nLSX

SX


Actor Ligand

M+nL

M+(n+1)L

S

S•

M+nL

S

-e–

S

M+nL

S

M+(n+2)L-2

S



Spectator Ligand


Redox-Active Ligand in Actor Role During Catalysis

! Novel reactivity derived from ligand centered radical in nature

Wachter, R. M., Montagne-Smith, M. P., Branchaud, B. P. J. Am. Chem. Soc., 1997, 119, 7743.

O OHOH

HO

OHHO

O OHOH

HO

OHO

Galactose Oxidase, O2

! Galactose oxidase, isolated from a fungal form, is a copper(II) containing enzyme which catalyzes the oxidation of primary alcohols to aldehydes

! This enzyme has been found to utilize a redox active tyrosine residue to facilitate the 2-electron oxidation process

CuIIO

(His496)N

(His581)N

OH2

O S (Tyr272)

(Tyr495)

(Cys228)

Catalytically active form of enzyme:


! Novel reactivity derived from ligand centered radical in nature

Wachter, R. M., Montagne-Smith, M. P., Branchaud, B. P. J. Am. Chem. Soc., 1997, 119, 7743.

CuIIO

(His496)N

(His581)N

O

O S (Tyr272)

(Tyr495)

(Cys228)

OH

R

H2O

R

CuIIO

(His496)N

(His581)N

OH2

O S (Tyr272)

(Tyr495)

(Cys228)

CuIIO

(His496)N

(His581)N

O

O S (Tyr272)

(Tyr495)

(Cys228)

R

HH

H

CuIO

(His496)N

(His581)NO S (Tyr272)

(Tyr495)

(Cys228)

GalactoseOxidase

H

H

H2O2

O2O

R

Substrate Participation as a Redox-Active Ligand

! Synthetic galactose oxidase mimics enable alcohol oxidation

Chaudhuri, P., Hess, M., Müller, J., Hildenbrand, K., Bill, E., Weyhermüller, T., Wieghardt, K. J. Am. Chem. Soc., 1999, 121, 9599.

1 (1 equiv.), Et3N (2 equiv.)

! The copper(II) complex (1) is capable of quantitatively oxidizingprimary alcohols to the corresponding aldehyde

! Complex 2, with a redox inactive zinc(II) is also capable ofoxidizing primary alcohols (approx. 150 TON in 24 hrs).

NMII

N

OO

t-Bu

t-Bu

t-Bu

t-Bu

M = Cu, 1Zn, 2

CH2Cl2

O

HMeMe

OH

>95% yield

! Kinetic studies show a kH/kD of 54 for methanol oxidation usingcomplex 1 indicating H-atom abstraction as the rate determiningstep in the process

Complex 1

Catalytic ethanol oxidation:


! Synthetic galactose oxidase mimics enable alcohol oxidation

Chaudhuri, P., Hess, M., Müller, J., Hildenbrand, K., Bill, E., Weyhermüller, T., Wieghardt, K. J. Am. Chem. Soc., 1999, 121, 9599.

OH

Me

AlcoholOxidation

H2O2

O2O

Me

NZnII

N

OO

t-Bu

t-Bu

t-Bu

t-Bu

NZnII

N

OH

O

t-Bu

t-Bu

t-Bu

t-Bu

OMe

NZnII

N

OH

OH

t-Bu

t-Bu

t-Bu

t-Bu

O

HMe

HH

NZnII

N

OH

OH

t-Bu

t-Bu

t-Bu

t-Bu

Ligand acts as electron donorand sink as well as an actor

in C–H abstraction


M+nL

M+nLSX

SX


Actor Ligand

M+nL

M+(n+1)L

S

S•

M+nL

S

-e–

S

M+nL

S

M+(n+2)L-2

S



Spectator Ligand


M+nL M+nLSX

SX-e–

S

M+nL

S

M+(n+2)L-2

S



Spectator Ligand


M+nL

M+(n+1)L

S

S•

M+nL

S


Actor Ligand



! Novel reactivity derived from ligand cetered nitrogen radical

King, E. R., Hennessy, E. T., Betley, T. A. J. Am. Chem. Soc., 2011, 133, 4917.Hennessy, E. T., Betley, T. A. Science, 2013, 340, 591.

NFe

N

Cl

Ar

Ad Ad

Ar = 2,6-Cl2-Ph (1)

PhN3

H H NBoc

Ph

1 (10 mol%)Boc2O (1 equiv.)

benzene, 65 °C

! Highly reactive FeIII–N• system enable the direct functionalization of alkanes in an analagous mannerto cytochrome P450 FeIV–O reactive center

! Dipyrrolomethane ligand is thought to behaveredox-innocently from previous DFT studies

Key intermediate:

NFeIII

N

Cl

Ar

Ad AdNR


! Novel reactivity derived from ligand cetered nitrogen radical

King, E. R., Hennessy, E. T., Betley, T. A. J. Am. Chem. Soc., 2011, 133, 4917.Hennessy, E. T., Betley, T. A. Science, 2013, 340, 591.

NFeII

N

Cl

Ar

Ad Ad

NFeII

N

NFeII

N

Cl N N2

Ph

NFeIII

N

Cl N

Ph

FeIIIN

H

HPh

NCl

N

NFeII

N

Cl NPh

Cl L

PhN3

–N2

H

L

NHPh

C–H AminationCycle

FeIIIN

H

Ph

NCl

NH


! Novel reactivity derived from ligand-centered carbene radical

Zhu, S., Ruppel, J. V., Lu, H., Wojtas, L., Zhang, X. P. J. Am. Chem. Soc., 2008, 130, 5042.

[Co(1)] (1 mol%)

CH2Cl2, rt

! Generation of carbenes using cobalt porphyrin complexes result in carbene withsignificant ligand centered radical character

PhN2

Ts

PhTs

99% yield, >99:1 dr,92% ee

! Radical nature of the reaction mechanism necessitates large chiral pockets inorder to achieve high selectivity

! Formation of nitrene ligands is also possible and can insert into activated C–H bonds

X = OMe, Y = H, 1



Zhu, S., Ruppel, J. V., Lu, H., Wojtas, L., Zhang, X. P. J. Am. Chem. Soc., 2008, 130, 5042.

[Co(1)] (1 mol%)

CH2Cl2, rtPh

N2

Ts

Ph

X = OMe, Y = H, 1

Ts

99% yield, >99:1 dr,92% ee

CoII

TsN2H

CoIII

TsH

CoIII

TsH

Ph

! Loss of nitrogen results in electron transfer from Co(II) center and formation of carbon centered radical



Lu, H., Jiang, H., Wojtas, L., Zhang, X. P., Angew. Chem. Int. Ed., 2010, 49, 10192.Zhu, S., Ruppel, J. V., Lu, H., Wojtas, L., Zhang, X. P. J. Am. Chem. Soc., 2008, 130, 5042.

[Co(1)] (2 mol%)

C6H5Cl, rtMeO2CN2

Ts

MeO2C

X = OMe, Y = H, 1

Ts

96% yield, 94:6 dr,89% ee

[Co(2)] (2 mol%)

C6H5CF3, 40 °C

95% yield

N N3S

OOMe

Me

N NHS

OOMe

Me

Co(2)

! Nitrene based systems proceed through a similar process


M+nL

M+nL M+nL

M+(n+1)L

SX

SX

S

S•

M+nL

S

-e–

S

M+nL

S

M+(n+2)L-2

S





Documents

AGC Redox Active Ligands - Princeton Universitychemlabs.princeton.edu/.../6/AGC_Redox_Active_Ligands.pdf · 2014. 2. 4. · "Redox-active, or 'noninnocent,' ligands have more energetically