Performance of DFT in Modeling Electronic

and Structural Properties of Cobalamins

JADWIGA KUTA,1 SEGUEI PATCHKOVSKII,2 MAREK Z. ZGIERSKI,2 PAWEL M. KOZLOWSKI1

1
Department of Chemistry, University of Louisville, 2320 S. Brook Street,
Louisville, Kentucky 40292
2
Steacie Institute for Molecular Science, National Research Council of Canada,
Ottawa, Ontario K1A 0R6, Canada

Received 23 November 2005; Accepted 14 December 2005

DOI 10.1002/jcc.20454
Published online in Wiley InterScience (www.interscience.wiley.com).

Abstract: Computational modeling of the enzymatic activity of B12-dependent enzymes requires a detailed under-
standing of the factors that influence the strength of the CoAC bond and the limits associated with a particular level
of theory. To address this issue, a systematic analysis of the electronic and structural properties of coenzyme B12
models has been performed to establish the performance of three different functionals including B3LYP, BP86, and
revPBE. In particular the cobalt–carbon bond dissociation energies, axial bond lengths, and selected stretching fre-
quencies have been analyzed in detail. Current analysis shows that widely used B3LYP functional significantly
underestimates the strength of the CoAC bond while the nonhybrid BP86 functional produces very consistent results
in comparison to experimental data. To explain such different performance of these functionals molecular orbital
analysis associated with axial bonds has been performed to show differences in axial bonding provided by hybrid
and nonhybrid functionals.

q 2006 Wiley Periodicals, Inc. J Comput Chem 27: 1429–1437, 2006

Key words: coenzyme B12; corrin; CoAC bond dissociation energy; inverse trans effect

Introduction
Derivatives of vitamin B12 that contain a unique CoAC bond
serve as a cofactor for many enzymatic reactions.1–6 Two bio-
logically active forms of vitamin B12 are known to bear alkyl
ligands: adenosylcobalamin (AdoCbl or coenzyme B12) with R ¼
50 -deoxy-50 -adenosyl, and methylcobalamin (MeCbl) with R ¼
CH3 (Fig. 1). The stable CoAC
bond holds the key to the enzy-
matic activities of AdoCbl and MeCbl-dependent enzymes, which
are quite different: the AdoCbl complex catalyzes radical rear-
rangement, while MeCbl transfers the methyl substituent to nucle-
ophilic substrates. In the case of AdoCbl, the cleavage is homo-
lytic, transiently yielding CoIICbl and an adenosyl radical,7 while
in case of the MeCbl the cleavage is heterolytic, yielding CoICbl
and a methyl cation.8 A precise understanding of the energetics of
the cobalt–carbon bond and the factors that control this cleavage
is an important goal in field of B12 chemistry. Substantial efforts
have been devoted towards dissection of the dynamics of CoAC
bond homolysis and the spectacular rate acceleration, exceeding
12 orders of magnitude, achieved within the active site of enzyme
in the presence of substrate.9–11 A variety of biochemical and bio-
physical methods have been applied to investigate how such a tre-
mendous acceleration is achieved and controlled by B12-dependent
enzymes. Despite these great efforts, the mechanism of the cata-
lytic activation still remains poorly understood.
Computational modeling of the CoAC bond activation em-
ploying realistic structural models of coenzyme B12 has been ham-
pered for a long time by size of the cofactor and its complexity
(Fig. 1). Earlier computations had only been carried out for simpli-
fied models, especially with respect to the corrin macrocycle12–14
or truncated cofactors without geometry optimization.15–17 Realis-
tic quantum chemical calculations employing density functional
theory (DFT) and models containing the entire corrin ring have
been reported only recently18–22 (see also summary in ref. 23).
Since this introductory work, there has been a growing interest in
modeling structure and electronic properties of the coenzyme
B12.24–36 Although these computational studies provided valuable
insights into the structure and the electronic properties of the
cofactor, the comparison with experimental data revealed that
performance of the B3LYP functional, which has been used in
majority of applications, is not as good as one could expect. In
particular, theoretical prediction of the CoAC bond dissociation
energies (BDEs) showed that B3LYP functional underestimates
Correspondence to: P. M. Kozlowski; e-mail: pawel@louisville.edu

q 2006 Wiley Periodicals, Inc.

1430 Kuta et al. Vol. 27, No. 12 Journal of Computational Chemistry
l l

Figure 1. Molecular structures of coenzyme B12 (AdoCbl; 50 -deoxy-50 adenosyl-cobalamin) and methyl-
cobalamin (MeCbl).

experimental values by approximately 10 kcal/mol. Although the recognized as one of the most accurate for structures, energies,
CoAC bond length was reasonably well reproduced, the CoANB and frequencies as has been demonstrated for many models of
associated with axial base was found to be longer by more than metalloenzymes.42–44
0.1 Å in comparison with experiment. It was suggested that Clearly, this issue requires further analysis and is the topic of
shallowness of the potential energy surface associated with the present work. This necessity is not only related to the
CoANB bond could be a plausible source of this discrepancy. strength of the CoAC bond but is also required for the proper
Only Rovira et al.32 correctly reproduced the CoANB bond length interpretation of spectroscopic and kinetic data. For example, re-
in MeCbl using the Car–Parrinello approach. cent theoretical work on NO binding to cobalamin45 has shown
The other unexpected result came from vibrational analysis the results strongly depend on the type of functional used in DFT
of MeCbl.37,38 The stretching frequency of the CoAC bond was
predicted to be 553 cm
1 in comparison to experimental value of
506 cm
1.39 To obtain a reasonable agreement with spectroscopic
data unusually low scaling factor of 0.86 was required to develop
Scaled Quantum Mechanical Force Field (SQM FF). This low
scaling factor is more typically required for Hartree–Fock force
constants and not for B3LYP, which is typically equal to 0.93.40
An important step toward resolving the issue of poor B3LYP
performance was recently presented by Jensen and Ryde.41 They
investigated why previously published B3LYP estimations of BDEs
for models of MeCbl have given such poor results and provided a
systematic analysis of possible BDE errors including such factors
as zero-point vibrational energy, basis set superposition error, ther-
mal, solvent or relativistic effects. They concluded that these fac-
tors are only of secondary importance, and that the problem is
associated with the B3LYP functional, specifically related to the
homolytic cleavage of metal–carbon bond. The problem with the
accuracy of the B3LYP energy calculations arises from the fact
that it is hybrid functional in combination with HF (Hartree–Fock)
exchange. Thus, one of the reasons for its failure in energy calcu-
lations seems to be the inclusion of an exact HF exchange. This
was a surprising outcome because the B3LYP functional is widely Figure 2. Molecular structure of BA[CoIII(corrin)]AR+ models.

Journal of Computational Chemistry DOI 10.1002/jcc

 Performance of DFT in Modeling 1431

Table 1. Selected Experimental Values of Co—C BDE (kcal/mol)
in Cobalamins.
No. System BDE Method
1 MeCbl 37 6 3 Thermolysis
2 MeCbl 36 6 4 Calorimetry
3 AdoCbl 31.5 6 1.3 Thermolysis
4 AdoCbl 30.9 6 4.1 Calorimetry
5 nPentCbl 28 6 2 Thermolysis
calculations. Systematic comparison of the experimental and the-
oretical data is further needed to understand how DFT methods
perform in modeling electronic and structural properties of vita-
min B12 derivatives. To accomplish this, six-coordinate cobala-
mins, denoted as B-[CoIII(corrin)]-R+ (Fig. 2), were employed in
the current work. Following our recent work on metalloporphir-
yns excited states,46 three different functionals B3LYP (the
Becke three-parameter hybrid functional with the Lee–Yang–
Parr correlation), BP86 (Becke–Perdew 1986 with no HF ex-
change) and revPBE (revised Perdew–Becke–Ernzerhof) have
been thoroughly tested and compared with experimental values
of CoAC BDEs (Table1) and with structural properties of co-
balamins having different bond lengths associated with the NBA
CoAC moiety (Table2). The particular focus in this work is
placed only on the type of functional rather on the basis set, sol-
vent, or relativistic effects, all of which have been recognized as
factors having secondary importance. All reported calculations
involving B3LYP and BP86 were carried out with the GAUS-
SIAN 03,47 while for revPBE the Amsterdam Density Functional
(ADF)48,49 suite of programs for electronic structure calculations
was used. In the case of B3LYP and BP86 the 6-31g(d) [for H,
C, N] and Ahlrich’s VTZ [for Co]50 basis sets were used. In the
case of revPBE calculations, the ADF standard Slater-type polar-
ized split valence (DZP) basis set was used, with [1s] frozen
cores on C, N, and [2p] frozen core on the Co atom.
Results and Discussion
Dissociation Energy of the CoAC Bond
Ref.
The energy of the CoAC bond dissociation is one of the most im-
56, 57 portant properties of cobalamins, and any reliable calculations
58 should provide an accurate estimation of this quantity. It is of pri-
11, 59 mary importance to understand which factors influence the CoAC
60 BDE and the limits associated with a particular level of computa-
61 tional modeling. To elucidate these factors and limits, the energy
of homolytic CoAC bond cleavage in BA[CoIII(corrin)]AR+ mod-
els was estimated as
þ
BDE ¼ BA½CoIII ðcorrinÞARþ 
opt
BA½Co ðcorrinÞopt
Ropt (1)
II
where the subscript ‘‘opt’’ denotes the energy of the optimized
structure employing one of the functionals under consideration. A
total of eighteen different models have been analyzed applying
three different functionals as summarized inTable 3. For each
functional only a subset of seven models with B ¼ DBI and R ¼
Me, Et, Rib, Ado, nPent, iProp, and tBut was selected for compar-
ison of BDEs with experimental data. Five experimental values of
CoAC BDEs were used to validate the accuracy of DFT calcula-
tions (Figs. 3 and 4).
Following our previous studies, we plotted BDEs as a function
of the CoAC bond length and fitted line BDE & A  r(CoAC) +
B to each set of points. Table4 summarizes parameters associated
with line fitting and shows that in all cases good linear correlation
is maintained, as can be judged from values of R2. For all three
functionals, energies diminish correctly with the changes in the
CoAC bond length. Although in all cases the lowering of the dis-
sociation energy correctly follows the CoAC bond lengthening,
comparison with experimental data shows that lines for both BP86
and B3LYP have a better linear fit than in case of revPBE. The
impression which one can get from Figure 3 is that lines associ-
ated with BP86 and B3LYP are nearly parallel in comparison to

Table 2. Selected Experimental Bond Lengths (Å) in Cobalamins with Esds in Parentheses.

Bond distances

No. System CoAN21 CoAN22 CoAN23 CoAN24 CoAC CoANB Ref.

1 CNCbl 1.875 (8) 1.908 (8) 1.917 (9) 1.875 (8) 1.858 (12) 2.011 (10) 62
2 CNCbl (KCl) 1.881 (3) 1.911 (3) 1.920 (3) 1.883 (3) 1.886 (4) 2.041 (3) 63
3 CF3Cbl 1.870 (9) 1.951 (10) 1.887 (10) 1.917 (9) 1.878 (12) 2.047 (10) 54
4 CHF2Cbl 1.894 1.911 1.891 1.887 1.949 (7) 2.187 (7) 64
5 MeCbl 1.88 (2) 1.97 (2) 1.93 (2) 1.89 (2) 1.99 (2) 2.19 (2) 65
6 MeCbl 1.877 (4) 1.922 (4) 1.918 (4) 1.874 (4) 1.979 (4) 2.162 (4) 66
7 AdoCbl 1.889 (9) 1.909 (9) 1.906 (9) 1.885 (9) 2.023 (9) 2.214 (9) 67
8 AdoCbl 1.880 1.916 1.914 1.866 2.030 (3) 2.237 (3) 68
9 Im—CNa 1.835 (9) 1.899 (8) 1.853 (9) 1.880 (8) 1.863 (11) 1.968 (9) 69
10 Im—Meb no data 1.97 2.09 70
11 cob(II)alamin 1.89 — 2.13 71
12 cob(II)alamin 1.88 (2) — 1.99 (3) 72

a
1H-imidazolylACNAcobamide.
b
1H-imidazolylAMeAcobamide.

Journal of Computational Chemistry DOI 10.1002/jcc

1432 Kuta et al. Vol. 27, No. 12 Journal of Computational Chemistry
l l

Table 3. DFT Optimized CoACR and CoANB Bond Lengths (Å) and CoACR BDEs (kcal/mol) in Cobalamins.

B3LYP revPBE BP86

Ba Ra CoAC CoANB BDE CoAC CoANB BDE CoAC CoANB BDE

DBI CN 1.871 2.125 — 1.856 2.177 — 1.852 2.110 —

CF3 1.954 2.186 — 1.995 2.249 — 1.952 2.185 —
Me 1.962 2.293 25.6 2.076 2.334 30.7 1.976 2.235 40.7
Rib 1.989 2.333 23.6 2.035 2.362 32.7 2.005 2.252 37.5
Ado 1.989 2.330 17.9a 2.033 2.327 26.7 2.005 2.247 31.9a
Et 1.990 2.358 19.5 2.038 2.368 29.5 2.012 2.257 85.1
nPent 2.021 2.505 12.3 2.078 2.589 23.6 2.048 2.346 26.7
iProp 2.027 2.586 13.0 2.105 2.549 23.8 2.066 2.337 26.8
tBut 2.091 2.841 3.1 2.199 2.645 16.0 2.146 2.471 17.5
DBIb — 2.251 — — 2.227 — — 2.160 —
Im CN 1.873 2.090 — 1.865 2.121 — 1.854 2.073 —
CF3 1.954 2.122 — 1.997 2.176 — 1.949 2.127 —
Me 1.962 2.218 28.0 2.010 2.236 33.7 1.976 2.170 41.3
Rib 1.989 2.234 26.0 2.040 2.280 31.9 2.007 2.184 39.1
Ado 1.988 2.227 18.9a 2.038 2.273 28.6 2.001 2.179 31.9a
Et 1.989 2.261 21.9 2.047 2.280 30.1 2.008 2.202 35.7
nPent 2.023 2.310 14.2 2.092 2.314 23.3 2.044 2.218 30.1
iProp 2.033 2.325 14.1 2.104 2.340 24.7 2.054 2.258 28.5
tBut 2.103 2.418 3.4 2.202 2.389 16.5 2.144 2.289 18.3
Imb — 2.213 — — 2.199 — — 2.126 —

a
B and R refer to B-[CoIII(corrin)]-R+.
b
Axial base in B-[CoII(corrin)]+.
c
Different conformation of adenosyl radical was used thus providing lowering of BDE in comparison with previous
results reported in Ref. 22.

experiment. The analysis of line parameters in Table 4 points out
that B3LYP functional significantly underestimates dissociation
energies, BP86 slightly overestimates while revPBE underesti-
mates, but to less extend than B3LYP functional. Increase of the
CoAC bond length gives the biggest change in energy in the case
of B3LYP, smallest in the case of revBPE, and nearly right for
BP86 (Figs. 3 and 4). The lack of experimental data precludes
making a similar assessment for much longer values of CoAC
bond lengths.
The best agreement with experiment is obtained in case of the
BP86 functional, which only slightly overestimates experimental
values (Fig. 4). Because the plotted data was not corrected for the
zero-point vibrational energy (ZPVE) or basis set superposition
error (BSSE), both these corrections should additionally lower the

Figure 3. Theoretically determined BDEs plotted as a function of Figure 4. Theoretically and experimentally determined BDEs plot-
the CoAC bond length in cobalamins with DBI as axial base ted as a function of CoAC bond length in cobalamins with DBI as
(squares, B3LYP; diamonds, BP86; triangles, revPBE). axial base (filled diamonds, BP86; empty circles, experiment).

Journal of Computational Chemistry DOI 10.1002/jcc

 Performance of DFT in Modeling
Table 4. Line Parameters and Linear Correlation Parameters for BDE as
Function of CoAC Bond Length.
A (kcal/mol Å
1) B (kcal/mol) R2
Experiment
115.16 264.53 0.9720
B3LYP
176.80 371.77 0.9333
BP86
133.69 303.19 0.9236
revPBE
83.69 200.27 0.7662
BDEs by few kcal/mol. The most significant correction is ZPVE,
which for ImA[CoIII(corrin)]AMe+ is equal to 4.92 kcal/mol em-
ploying the BP86 functional and mixed basis set, while the BSSE
correction should be around 1 kcal/mol according to Jensen and
Ryde.41 Comparison of the theoretical data obtained with the
revPBE functional implies that performance of this functional is
not as reliable as BP86. The BDEs are slightly underestimated
(Table 3), but the optimized CoAC bond lengths are too long in
average 0.05 Å in comparison to the experiment (Fig. 3). This
overestimation of bond length causes a shift of the line represent-
ing the revPBE functional toward much longer cobaltAcarbon dis-
tances. The worst performance in terms of BDEs is displayed by
the B3LYP functional, which underestimates BDEs by more than
10 kcal/mol, but at the same time the optimized CoAC bond
lengths remain in good agreement with experiment. They are
slightly shorter in comparison to the BP86 functional but more
reliable than those provided by revPBE.
The trans axial base influence on BDEs was also examined
in the present work by replacing DBI with Im (Table 3). Imidaz-
ole was combined with a series of axial ligands and for each of
structures the BDE was computed. Systematic analysis of the
energies associated with the homolytic cleavage of CoAC bond
shows that the influence associated with DBI replacement is
small in term of energy and does not depend on the type of func-
tional. In particular, results plotted for BP86 functional (Fig. 5)
show that lines are almost parallel with very similar slopes
(
133.69 and
131.10) and intercepts (303.19 and 298.70), re-
Figure 5. BP86-determined BDEs plotted as a function of the
CoAC bond length in cobalamins with DBI and imidazole as axial
bases (squares, imidazole; diamonds, DBI).
Journal of Computational Chemistry
1433
Figure 6. Theoretically determined CoANB distances plotted as a
function of CoAC distances in cobalamins with DBI as axial base
(squares, B3LYP; triangles, revPBE; diamonds, BP86).
spectively. The presence of DBI leads to lower values, but the av-
erage difference does not exceed 1 kcal/mol in terms of BDEs.
NBACoAC Axial Bond Lengths
The other performed test was analysis of the axial bonds lengths
in models of c factors B12 (Fig. 2). Structural correlation between
the nature of the axial ligands and bond distances in NBACoAC
moiety has been a topic of experimental and theoretical studies in
conjunction with the anomalous trans effect.51–54 The anomalous
(or inverse) trans effect emerges when the change in R lengthens
or shortens both the interligand CoAC and the CoANB distances.
The origin of this effect is a consequence of an unusual combina-
tion of poor
/-donation by the base and unusually strong
-don-
ation by the alkyl group R.33 For the purpose of this analysis we
selected nine structures with different electron donating/with-
drawing character of the R groups (Table 3). The correlation
between the CoAC and the CoANB distances was plotted in
Figure 6, together with values of optimized bond lengths. To
each set of points, a line CoANB & Cr(CoAC) + D was fitted
T
( able 5) to establish qualitative correlation between axial bond
lengths (Figs. 6 and 7). To obtain each line, only structures with
DBI as an axial base were analyzed together with a set of nine
different R groups to cover the experimentally determined bond
lengths (Tables 2 and 3). However, the scarcity and concentra-
tion of experimental data limit the reliability of the computed
slope.
Table 5. Line Parameters and Linear Correlation Parameters for CoAN
Bond Length as Function of CoAC Bond Length.
C D (Å) R2
Experiment 1.2732
0.3455 0.9396
B3LYP 3.4151
4.3939 0.8754
BP86 1.2484
0.2338 0.9569
revPBE 1.5035
0.6762 0.7571
DOI 10.1002/jcc
1434 Kuta et al. Vol. 27, No. 12 Journal of Computational Chemistry
l l

CoANB Bond Length in cob(II)alamins

The other important test of DFT accuracy is a correct prediction

of the structural changes associated with homolytic cleavage of
the CoAC bond. Of particular interest is the change of the
CoANB bond length as a consequence of the following reaction

BA½CoIII ðcorrinÞþ ARþ ! BA½CoII ðcorrinÞ þ R: (2)

The length of the CoIIANDBI has been determined experi-

mentally71 and its value 2.13 Å is shorter by about 0.1 Å in
comparison to coenzyme B12 (CoIIIANDBI ¼ 2.237 Å). The opti-
mized CoIIANB bond employing B3LYP was found to be equal
to 2.251 Å in the case of DBIA[CoII(corrin)]+, while 2.213 Å
for ImA[CoII(corrin)]+. The same calculations were performed
Figure 7. Theoretically and experimentally determined CoANBase
with BP86 and revPBE. BP86 gives 2.160 Å for DBIA
distances plotted as a function of CoAC distances in cobalamins with
[CoII(corrin)]+ and 2.126 Å for ImA[CoII(corrin)]+, while
DBI as axial base (filled diamonds, BP86; empty circles, experiment).
revPBE gives 2.227 and 2.199 Å, respectively. The calculated
values confirm the trend observed in Figure 6, where the
The lines representing the BP86 and revPBE functionals (Fig. 6) CoANB bond lengths calculated with B3LYP gives the highest
are nearly parallel to experiment with similar slopes (Table 5). The values. All three functionals slightly overestimate experimental
B3LYP functional exhibits very different behavior and has a much data; however, BP86 again gives the best comparison with the
bigger slope. The lines corresponding to experiment and to the experiment among three investigated functionals. The higher val-
B3LYP functional intersect each other around ‘‘short’’ distances ues of CoANB bond length were obtained with DBI as axial
representing electron withdrawing groups like ACN or CF3. base for all three functionals. This observation reflects data col-
Although the optimized CoAC bond lengths are close to experi- lected in Table 3, when values of CoANB bonds for DBI and
mental values, the CoANB distances are too long, which in conse- imidazole are compared.
quence causes a very steep increase for the line representing
B3LYP data. For this reason we noticed previously that for certain
Interligand NBACoAC Vibrations
R groups like iProp or tBut the trans axial bases are not part of the
Co coordination sphere.19,33 This indeed is an artifact related to Analysis of the interligand vibrations including the CoAC and
B3LYP functional; BP86 predicts much shorter distances. The CoANB bonds can provide further insight into the performance
revPBE functional produces both axial distances too long in com- of functionals under consideration. For this purpose DFT analysis
parison to experiment. The average overestimation in the case of of the ImA[CoIIIA(corrin)]AMe+ model was performed with
CoANB bond is about 0.10 Å, while in the case of CoAC 0.05 Å. B3LYP and BP86 functionals. The most important interligand
Also, in the case of revPBE, the linear fit is much worse than in vibration is the CoAC stretch. The frequency of this vibration cal-
case of BP86 functional (Table 5).
Analysis of the optimized models with two different bases
(DBI and Im) was also provided. This comparison for BP86 func-
tional is shown on Figure 8. Analysis of all optimized structures
allows us to establish that each trans axial base produces a positive
linear correlation between the CoANB and CoAC bonds, but the
two lines fitted for the different bases have different slopes
(
0.2338 and 0.5770) and intercepts (1.2484 and 0.8021). One
can note that the CoAC bond length stays basically identical for
the same R substituent, when DBI is replaced by Im (Table 3).
A different situation occurs for the CoANB bond lengths. DBI
gives higher values of bond lengths, which most likely reflect its
different basicity. For the two axial bases considered, the differ-
ences become more apparent with bond lengthening. For tBut,
the difference is approximately 0.2 Å. The third set of points on
Figure 8 represents the available experimental data for imidazole
as the axial base (Table 2). One can note that BP86 accurately Figure 8. BP86-determined CoANB distances plotted as a function
reproduces the CoAC bond length, while in the case of CoANB of CoAC distances in cobalamins with DBI and imidazole as axial
BP86 it gives values about 0.1 Å too long, when compared with bases (filled squares, imidazole; filled diamonds, DBI; empty circles,
the experiment. experimental data for imidazole).

Journal of Computational Chemistry DOI 10.1002/jcc

 Performance of DFT in Modeling 1435

Figure 9. Orbital energy diagram for 1+, 1
,
2+,
2
,
3+, and
3
molecular orbitals of
ImA[CoIII(corrin)]AMe+ determined with B3LYP and BP86 functionals and their contours determined
with BP86 functional.

culated using B3LYP functional is 553 cm
1, while 535 cm
1
corresponds to BP86. The same trend is observed for calculated
values of CoANB stretching, where B3LYP displays a lower fre-
quency (133 cm
1) while BP86 a higher frequency (148 cm
1),
consistent with the inverse trans effect (Table 3). Although those
results seem to confirm better performance of BP86 functional,
this is not so critical for frequency analysis. For both functionals
the frequencies for the CoAC bond stretch are overestimated,
and the force constants have to be scaled to obtain reasonable
agreement with experiment. Although BP86 predicts closer value
to the experiment, that is, 505 cm
1, the overall performance
from a statistical point of view is better for B3LYP. Conse-
quently, the latter was used in recent DFT analysis of Co-alkyl
and Co-adenosyl vibrational modes in B12-cofactors.55
Summary and Discussion
DFT has become a popular method for studying the structure
and electronic properties of large molecules. Its accuracy has
been validated for wide range of organic molecules and mole-
cules with transition metals. This is not yet the case for many
biological complex systems including coenzyme B12.
Several structural models of coenzyme B12 have been investi-
gated in the present work showing that the BP86 functional gives

Journal of Computational Chemistry DOI 10.1002/jcc

1436 Kuta et al. Vol. 27, No. 12 Journal of Computational Chemistry
l l
the best agreement with experimental data and should be further
considered as more appropriate than more commonly used B3LYP
functional. In that sense our present study confirms and extends 12.
previous work of Jensen and Ryde.41 Furthermore, they suggested
13.
that the basic problem with performance of B3LYP functional
14.
arises from Hartree–Fock inclusion, and that the general problem 15.
of the B3LYP functional for homolytic metal–carbon dissociation 16.
energies in tetrapyrollic system is cased by the differing correla-
tion energies of open- and closed-shell complexes with a different 17.
number of unpaired electrons. Although this argument can be ap-
plied to explain difficulties associated with the cobal–carbon bond 18.
cleavage it cannot be simply extended to explain problematic per-
formance associated with the correct reproduction of the NBA 19.
CoAC axial bond lengths (Fig. 6).
20.
To further elucidate the problem associated with the B3LYP
21.
functional we performed population analysis for ImA[CoIII(corrin)]
AMe+ model using both B3LYP and BP86 functionals and ex- 22.
tracted six molecular orbitals (MOs) that are directly involved in
the NImACoACMe bonding. Following previous analysis,33 the 23.
prerequisite for description of interligand bonding is formation 24.
of three MOs described as strongly bonding ( 1), strongly anti- 25.
bonding ( 3*) and of mixed character
2, which is bonding with
respect to CoACMe and antibonding with respect to CoANIm. 26.
The additional complication arises from mixing of
’s orbitals 27.
with the corrin  orbital, with the dxy orbital of Co and with px
28.
and py orbitals on NIm. The orbital energy diagram and contours
of those orbitals for both B3LYP and BP86 functionals are sum- 29.
marized in Figure 9. Althopugh both functionals predict qualita- 30.
tively the same orbital energy pattern, they give quantitatively 31.
different energetic description. The bonding orbitals resulting
form B3LYP are energetically too low in comparison to BP86, 32.
while antibonding orbitals are too high. The same problem has 33.
been noticed in the case of excited states analysis for nickel por-
phyrins where it was found that B3LYP functional produces 34.
qualitatively incorrect energies of the d orbitals on the Ni atom 35.
leading to mislocations of states originating from a transfer of
an electron between the metal and the porphyrin ring.46 Nonhy- 36.
37.
brid BP86 functional produces similar ordering of the excited
electronic states as B3LYP, but gives better qualitative agreement 38.
with experimental results. In the case of cobalamins, the B3LYP
functional gives too weak axial NBACoAC bonding description 39.
which consequently affects strength of both axial bonds.
40.
41.
References 42.
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