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A Two-Scale Approach to Electron Correlation
in Multiconfigurational Perturbation Theory
Pooria Farahani,[a] Daniel Roca-Sanjuan,[b] and Francesco Aquilante*[a,c]
We present a new approach for the calculation of dynamic
electron correlation effects in large molecular systems using
multiconfigurational second-order perturbation theory
(CASPT2). The method is restricted to cases where partitioning
of the molecular system into an active site and an environ-
ment is meaningful. Only dynamic correlation effects derived
from orbitals extending over the active site are included at the
CASPT2 level of theory, whereas the correlation effects of the
environment are retrieved at lower computational costs. For
sufficiently large systems, the small errors introduced by this
Introduction
Recent developments in multiconfigurational quantum chemis-
try,[1] in particular within the complete active space self-
consistent field second-order perturbation theory (CASSCF/
CASPT2) method[2] have made it feasible to perform such cal-
culations on much larger molecular systems and with more
extensive basis sets. The limit in basis set size for routine
investigations has thereby been extended to the range 1000
2000 basis functions.[37] This has been possible through the
introduction of the Cholesky decomposition (CD) representa-
tion of the electron repulsion integrals,[3,4,8,9] that later on
evolved into the so-called ab initio density fitting approxima-
tion.[1015]
Cholesky-based density fitting can today be used at most
levels of theory[16] ranging from the integral evaluation,
through SCF and CASSCF to multiconfigurational second-order
perturbation theory. A detailed account of the implementation
of this approximation to CASSCF wave functions can be found
in the study of Aquilante et al.[4] The use of CD approximation
at the CASPT2 level of theory was first illustrated in an applica-
tion to the electronic structure of the low-lying electronic state
of the complex CoIII(diiminato)(NPh).[3] This calculation on a
system with 43 atoms utilized a general contracted Gaussian
basis set with a total of 869 basis functions. A two-root multi-
state calculation took 3.2 days wall time on a single AMD
Opteron 148, 2.2 GHz workstation, equipped with 1 GB of
memory. This should be compared with the time used for the
evaluation of the Cholesky vectors, 3.5 h, and the time per
iteration for the CASSCF calculations, of 3.9 min (using a 10
in10 active space). Since this first application, it became clear
from these numbers that the bottleneck in the use of the CD-
based CASSCF/CASPT2 method with large basis sets and many
electrons would be the CD-CASPT2 step. In fact, systems with
few hundred atoms can be treated efficiently at the CASSCF
level by means of the local exchange screening algorithm[17]
REVIEW
approximation are contrasted by the substantial savings in
both storage and computational demands compared to the
full CASPT2 calculation. Provided that static correlation effects
are correctly taken into account for the whole system, the pro-
posed scheme represent a hierarchical approach to the elec-
tron correlation problem, where two molecular scales are
treated each by means of the most suitable level of theory.
C 2014 Wiley Periodicals, Inc.
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DOI: 10.1002/jcc.23666
based on localized Cholesky orbitals.[18] Such gracious compu-
tational scaling is lost when performing the subsequent CD-
CASPT2 calculation, where the only possibility explored so far
to lower its computational costs has been to use the frozen
natural orbital (FNO) approximation,[19,20] that reduces the size
of a large secondary orbital space while retaining the accuracy
of the method.
Here, we shall describe and illustrate an approach that can
be used to speed-up even more drastically CD-CASPT2 calcula-
tions by reducing the size of the secondary, as well as the
inactive orbital spaces. The approach is useful in cases where
the active orbitals are located in a limited region of the mole-
cule, thus belonging to an active site, in contrast to the
remaining portion of the molecule (environment). As dynami-
cal correlation effects are known to be short-ranged, it seems
reasonable to assume that relative energies can be computed
just by taking into account the correlation energy contribution
arising from the active site (henceforth indicated by A). Using
a localization procedure that will be described below, it is
then possible to divide the inactive and secondary orbital
[a] P. Farahani, F. Aquilante
Department of Chemistry - Angstrom, The Theoretical Chemistry Pro-
gramme, Uppsala University, P. O. Box 518, SE-751 20, Uppsala, Sweden.
E-mail: francesco.aquilante@gmail.com
[b] D. Roca-Sanju an
Instituto de Ciencia Molecular, Universitat de Valencia, P.O. Box 22085, ES-
46071, Valencia, Spain
[c] F. Aquilante
Dipartimento di Chimica G. Ciamician, Universit a di Bologna, V. F. Selmi
2, 40126, Bologna, Italy
Contract grant sponsor: Swedish Natural Science Research Council (VR).;
Contract grant sponsor: Spanish MINECO (Ministero de Economa y
Competitividad); Contract grant number: CTQ2010-14892; Contract grant
sponsor: Juan de la Cierva programme; Contract grant number: JCI-
2012-13431; Contract grant sponsor: Italian Ministry of Education and
Research (MIUR; F.A.); Contract grant number: RBFR1248UI
C 2014 Wiley Periodicals, Inc.
V
Journal of Computational Chemistry 2014, 35, 16091617 1609
 REVIEW WWW.C-CHEM.ORG
spaces into two partitions such that one of them has no con-
tributions from the atomic basis functions in the active site.
The occupied (secondary) orbitals belonging to the latter can
be left frozen (deleted) in the CASPT2 calculation. In this pic-
ture, the nondynamical correlation effects are nonetheless
taken into account without additional approximations, as the
CASSCF calculation is performed for the entire system. Finally,
an estimate of the dynamical correlation energy due to the
environment (henceforth, B) can still be computed. As shown
in the next section, by neglecting the coupling terms between
A and B in the CASPT2 equations, the set of amplitudes for B
can be easily determined at the cost of second-order Mller
Plesset perturbation theory (MP2).
A similar approach has been proven effective in reducing
the costs of MP2 calculations.[21] More generally, the idea of
partitioning a large molecular system into regions to be
treated at different levels of theory is certainly not new. Multi-
scale modeling by means of embedding methods using the
charge-densities as the only descriptors for the environment
has become very popular.[2224] Although not required in the
exact embedding theory, spatial separation between the
active site and the environment is a condition for robustness
in the application of the approximate protocols.[25] In theoreti-
cal studies of large molecules for which combined quantum
mechanics-quantum mechanics (QM/QM) or quantum
mechanics-molecular mechanics (QM/MM) models can be
applied, also the ONIOM scheme[26] is very widespread. How-
ever, in these cases the molecule is typically split into parts,
with the consequence that dangling bonds need to be satu-
rated with link atoms. This artificial split of the molecule pre-
cludes any possibility to recover the exact result of the full
molecular calculation. That is not the case, at least in principle,
for analogous approaches[21,2733] based on the local correla-
tion paradigm of Pulay.[34] These so-called local correlation
methods have gone from the accurate and efficient evaluation
of ground-state correlation energy[21,29,34,35] to computational
techniques for spectroscopy of large molecules.[27,30,31,33] The
present work can be considered an attempt to investigate the
applicability of some of these ideas in a new context, namely
that of multiconfiguration wave function theory.
Methodology
Definition of the active site
The active space in CASSCF/CASPT2 calculations is in many
cases of interests confined to a particular region of the mole-
cule, comprising very few atoms. Moreover, only a very limited
number of orbitals belonging to these atoms play a role in
nondynamical correlation effects, and therefore, the number of
active orbitals (Nact) is usually very small (limited to about 14
18 units). In such situations, the bottleneck of the CASPT2
treatment is represented by the fact that the number of exci-
tations in the first-order wave function (see Andersson and
Roos[2]), increases rapidily with the size of the atomic orbital
(AO) basis set. In particular, due to the presence of external
excitations (two orbital index belonging to the secondary sub-
1610 Journal of Computational Chemistry 2014, 35, 16091617
space), the dimensionality of the linear equations for CASPT2
amplitudes grows with the fourth power of the system size.
As anticipated in the previous section, most of these compu-
tational complexities can be alleviated by moving from a canoni-
cal orbital picture to one based on localized orbitals. The
definition and uses of such localized orbital approach traces out
the ideas central to the local correlation methods of Pulay.[34]
Here and in the following, greek subscripts are used to refer to
AOs, whereas p, q, r,. . . are used to denote general molecular
orbitals (MOs). For inactive and secondary MOs we use sub-
scripts i, j, k, . . . and a, b, c, . . . , respectively, whereas t, u, v, . . .
identify active orbitals. As the active orbitals are assumed to be
localized, they naturally define an active site (A) of the molecule,
in contrast to the remaining set of atoms, the environment (B).
For a given active orbital uu and a given atom X, we compute its
P
atomic gross Mulliken population, QuX 5 < uuX juu > 5 lX m CluX
SlX m Cmu (where C is the MO coefficient matrix, S is the AO overlap
matrix and lX indicates that only the AO basis functions on
atom X are included in the sum). For each atom X of the mole-
cule, the euclidean norm of QX 5fQuX ; u51; Nact g is compared
against a given threshold (s) to assign X to the region A or B.
Once the active site has been defined, the inactive orbitals
have to be localized. In principle, any of the standard localiza-
tion techniques can be used for this purpose,[36,37] but here we
used instead the so-called Cholesky MOs, proposed by one of
the present authors,[18] and proven useful in combination with
screening techniques for building Fock-type matrices.[17] In con-
trast to standard techniques, the Cholesky localization is noni-
terative as it requires only one CD of the AO density matrix
P
computed from the inactive orbitals, DIlm 5 inact k Clk Cmk . Despite
the somewhat less optimal locality of the resulting orbitals, the
computational advantages compared to standard techniques
are sufficient to justify our choice in the present context. Each
localized inactive orbital ui is, then, assigned to either A or B
depending on the absolute value of QiA 5 < uiA jui >, where the
symbol uiA is used to indicate the same ui but truncated to the
AO basis functions on atoms of the active site only.
For the virtual orbitals, the situation is more involved, as
standard localization techniques can suffer from convergence
problems. Observing instead that the AO basis is local by defi-
nition, it is tempting to use these orbitals to span the second-
ary space. Orthogonality to the remaining subspaces is
ensured by projecting out these components, and therefore,
producing the so-called projected atomic orbitals
(PAOs).[34,38,39] These orbitals constitute a nonorthogonal and
linearly dependent basis for the secondary space. In local cor-
relation methods[27,30,31,3335,3842] linear dependence is elimi-
nated by diagonalizing the overlap matrix and subsequently
removing orbitals corresponding to zero eigenvalues. Such
procedure is in principle performed for each pair of occupied
orbitalsone such an overlap matrix has, therefore, linear
dimension proportional to the union of the small subsets of
PAOs that are accessible by excitation from a given localized
occupied orbital (orbital domains). For the definition of these
orbital domains, each PAO is formally assigned to the atom
center of the corresponding AO basis function (e.g., as in Ham-
pel and Werner[38]). In our case, this approach is perfectly
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suited to partition the secondary space between the regions A
and B. However, as the removal of linear dependencies is per-
formed separately for the PAOs assigned to each region, it is
not guaranteed that the overall number of resulting orbitals
(orthonormal within each region) is identical to the initial
number of canonical secondary orbitals. This is a typical situa-
tion in local correlation methods, where a much larger of sec-
ondary orbitals (if summed over all domains) is obtained.
Although not of crucial importance for our method, we opted
for an approach free from such a potential overparametriza-
tion. As explained in Ref. [18], a set of nonorthogonal but line-
arly independent PAOs spanning the entire secondary space
can be obtained through CD of a properly defined density-
type matrix in AO basis:
DVlm 5S21 2Dlm ;
where S is the overlap matrix in AO basis and D is the projec-
tor onto the occupied (inactive 1 active) space. These set of
Cholesky MOs retain most of the locality of the initial PAOs
and their number is identical to the initial number of canonical
secondary orbitals. Moreover, as the CD procedure is per-
formed stepwise by selecting the current largest diagonal ele-
ment of the density-type matrix, each Cholesky MO can be
assigned to the atom carrying the corresponding AO basis
function. In this way, there is no ambiguity in partitioning
these orbitals between the two regions A and B. After that,
the secondary orbitals in each region can be separately ortho-
normalized, therefore, keeping their local character.
The final step before the energy evaluation itself consists in
deriving a new set of canonical orbitals for each of the two
regions, such that the simplicity of the calculation in canonical
basis can be retained, and existing computer codes can be used
with no extra programming effort. These (localized) canonical
orbitals and their orbital energies can be obtained from the initial
canonical orbital energies via diagonalization of the partial
(restricted to orbitals in either A or B) occupied (virtual) Fock
matrix, F5UUT , where U is the orthogonal transformation matrix
for the occupied (virtual) orbital localization. In such canonical
basis, standard CASPT2 codes can be used without any modifica-
tion. The only thing that changes compared to the full calculation
is the size of the inactive and virtual orbital space in input, now
restricted only to canonical orbitals localized in A. For this reason,
a name such as freeze-and-delete (FD) CASPT2 seems appropri-
ate for this approach.
CASPT2 formulated in localized orbital basis
In CASPT2, the first-order correction to the CASSCF wave func-
tion W0 includes contributions from only singly and doubly
excited configurations, thus:
X X
W1 5 tqp E^pq W0 1 E pq E rs W0 5
pr ^ ^
tqs
pq pqrs
where in the singlet one-electron excitation operators the indi-
ces q, s are restricted to inactive or active orbitals and p, r to
active or secondary orbitals. The set of (nonredundant) ampli-
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tudes t is determined through the solution of the following
linear equations
X
^ 0 > ;
< Um jH^ 0 2E0 jUl > tl 52 < Um jHjW (3)
l
with H^ 0 and E0 5 < W0 jH^ 0 jW0 > representing the zeroth-
order Hamiltonian and zeroth-order energy, respectively.
Details about the solution of eq. (3) can be found in Ref. [43]
and the references therein.
Assuming the parametrization of eq. (2), any set of orbitals,
separately spanning the three subspaces (inactive, active, and
secondary) can be used. In this work, we want to prove the
advantages of using localized orbitals for the inactive and sec-
ondary subspaces in situations where the active orbitals are
(1) confined to a small region of the molecule. We start by recall-
ing the basic assumption of single-reference local correlation
method, for which the first-order wave function can be
expressed as (see, e.g., Schutz et al.[35]:
XX
W1 5 ~t ab ab
ij Uij : (4)
ij ab2ij
The symbol [ij] indicates the so-called pair domain, thus the
union of the orbital domains of ui and uj . As each orbital is
supposedly localized, only pairs of orbitals that share at least
one atom (strong pairs) need to be included in the expansion
eq. (4) to recover about 90% or more of the correlation
energy.[35] Adapting this logic to CASPT2, and assuming the
partitioning of the molecule in active site and environment
described above, we can replace the doubly excited configura-
tions in eq. (2) with the following approximate expression:
A
X B
X
~t pr ~t ab
W1  ^ ^ 0
qs E pq E rs W 1
^ ^ 0 :
ij E ai E bj W (5)
pqrs aibj
Moreover, the set of linear eq. (3) splits into two uncoupled
subsets, where the one corresponding to the orbitals in B is
now equivalent to an MP2 model. In our (localized) canonical
basis, this implies that the approximate contribution to the
correlation energy due to B is given in a noniterative and
straightforward manner by the canonical MP2 expression. The
total PT2 energy can, then, be approximated as
A1B A
ECASPT2  ECASPT2 1E2B : (6)
The complexity of the CASPT2 calculation on the whole sys-
tem is, therefore, reduced to that of the calculation of the
(small) set of amplitudes associated with the orbitals assigned
to the active site. As discussed in Ref. [3], in fact, the need to
store/retrieve the set of two-electron integrals in MO basis in
X the present implementation of the CD-CASPT2 method can
tl Ul ; (2)
l
seriously limit its efficiency and capability for large molecules
and large AO basis sets. Conversely, the CD-MP2 energy
expression in canonical orbital basis can be computed without
storing the (aijbj) integrals on disk[10,44] and it is, therefore,
much more affordable than the corresponding CD-CASPT2
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calculation. Furthermore, efficient linear-scaling algorithms for
local correlation methods have been developed over the
years[35,41] that could be used for the MP2 energy correction
to break down the computational scaling of this part of the
calculation. We finally highlight the fact that although the
expression for computing E2B is identical to the well-known
MP2 formula, the resulting value will in general be very differ-
ent from the one obtained using the closed-shell HF reference,
due to the use of pseudocanonical orbitals, obtained by diago-
nalization of the CASSCF Fock matrix.
Before closing this section, it is worthwhile comparing more
in detail FD-CASPT2 with local correlation methods. Although
they share a common origin, there are differences to be
pointed out. For instance, in local correlation methods one can
approach the exact evaluation of the correlation energy by
including pairs of orbitals which do not have common atoms
in their respective domains. Depending on the relative dis-
tance, so-called weak and distant pairs are included in the
model[35,41,42,45] at various degrees of approximation. Due to
the fact that the bottleneck in these calculations is determined
by the treatment of strong and weak pairs only,[45] the overall
scaling of the method can be maintained linear in virtue of
the linear scaling number of such pairs in localized orbital
basis. In our case, the CASPT2 treatment is performed only for
the orbital pairs belonging to the active site, thus it is equiva-
lent to select some but not all strong pairs for the highest
level of theory. The environment is treated at MP2 level. For
infinite separation between the two regions, this approxima-
tion is exact, but in reality our method suffers from the
neglect of (nonstrong) pairs between the regions. A consistent
way to approach the exact CASPT2 correlation energy for the
entire system seems, therefore, impossible. Conversely, similarly
to the subtractive QM/QM scheme[26] we can include in an
approximate way the contribution to the correlation energy
due to the nonstrong pairs if we write the total PT2 energy of
the system as
A1B A
ECASPT2  ECASPT2 1E2A1B 2E2A 5ECASPT2
A
1Eenv 5EFD2CASPT2 : (7)
The above expression defines the energy values computed
with the present FD-CASPT2 scheme and used throughout this
publication. As the active site contains partially occupied orbi-
tals, we must attach a meaning to the MP2-type energies of
eq. (7). Similarly to the strategy used in the FNO approxima-
tion,[19] we associate to W0 a single Slater determinant in
which all orbitals with negative energy are doubly occupied.
The active orbitals (fractionally occupied space) with nonnega-
tive energy are excluded from the list to avoid problems with
the onset of orbitals near degeneracy (e.g., in the study of dis-
sociation processes). All the remaining orbitals with nonnega-
tive energy define the secondary space. This hypothetical
single-reference is used for computing E2A1B and E2A energy
contributions from solely its doubly excited determinants.
The final consideration is about the computational scaling
of the FD-CASPT2 method. Due to the use of canonical orbi-
tals, although the latter are confined to one of the two regions
all possible pairs within each region are treated equivalently.
1612 Journal of Computational Chemistry 2014, 35, 16091617
This implies that linear scaling of the computational costs can-
not be achieved whenever the contribution from the environ-
ment is to be included. Werner and coworkers[29] have shown
that by retaining a fully localized orbital picture, it is possible
to devise multiregion type correlation approaches for single-
reference wave functions. Conversely, we feel that the scaling
of the FD-CASPT2 is not the prominent issue, if analyzed in
light of the overall reduction of computational costs compared
to the CASPT2 calculation for the whole molecule.
Sample Calculations
We have investigated the reliability of the FD-CASPT2
approach, with the MP2 corrections of eq. (7) for the environ-
ment, in a typical application of the CASPT2 method, namely
spectroscopy of isolated and solvated molecules.
Our tests have been performed using different thresholds
(s) for FD-CASPT2 and comparison with the full CASPT2 results,
using a development version of the MOLCAS quantum chemis-
try software.[46] To minimize the effect of weakly interacting
intruder states in some CASPT2 computations, the imaginary
level-shift technique (0.2 au) has been applied. To correct the
systematic error of the CASPT2 method affecting the processes
where the number of paired electrons is changed, the ioniza-
tion potential electron affinity (IPEA) modified zeroth-order
Hamiltonian has been used with a value of the IPEA parameter
of 0.25 au.[47,48] The Gaussian 09[49] program has been used
for geometry optimization with the DFT and MP2 methods.
Deoxythymidine
We start by benchmarking the vertical electronic excitation
energies (EVA) and the lowest vertical ionization potential (VIP)
of the DNA nucleoside deoxythymidine (dT). As explained else-
where,[50,51] the electron is removed from the highest-
occupied MO of the nucleobase, that is, the thymine moiety,
in the ionization process. The same holds for the excitation,
which is localized in the thymine chromophore. Therefore, this
system is expected to be a good candidate for analyzing the
accuracy of the FD approach versus the CASPT2 method.
According to previous theoretical studies,[50,52] the sugar moi-
ety does not seem to change significantly the absorption ener-
gies, but much larger changes can be expected for the VIP
property. In particular, a change of 0.12 eV was reported by
Improta and Barone for the EVA related to the lowest-lying pp*
excited state.[52] Conversely, Rubio et al.[50] predicted a
decrease of 0.62 eV in the VIP of the dT system with respect
to the thymine nucleobase.[50] Next, we analyze the perform-
ance of the FD-CASPT2 approach in the dT system as com-
pared with the standard CASPT2 and taking into account the
results related to the isolated nucleobase.
The ground-state equilibrium structure of dT has been opti-
mized at the MP2/cc-pVDZ level of theory in the anti confor-
mation, that is, the optimized structure has the nucleobase
oriented away from the deoxyribose as in the B-DNA form. At
the optimized geometry, the FD-CASPT2 method with different
thresholds (s) has been used to compute the EVA energies of
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Figure 1. Molecular model of the deoxythymidine. Atoms in orange color
are the ones assigned to the active region. a) s 5 0.010.4 and b) s 5 0.5.
the three lowest-lying excited states of the molecule. The
double-f ANO-S-VDZP basis set[53] has been used for these cal-
culations. The active space comprises 10 electrons in 8 active
orbitals (10in8), including the valence p and p* orbitals of the
nucleobase moiety. Figure 1 depicts the selected active region
(region A) using different thresholds (s). Eight atoms are
assigned to the active region in the FD-CASPT2 computations
with thresholds s ranging from 0.01 to 0.4 (orange), which cor-
respond to the atoms belonging to the p conjugated system.
Taking into account that the natural orbitals of the CAS(10in8)
space are delocalized over these atoms, the selection can be
considered as optimal. It is confirmed by the results compiled
in Table 1. Hence, a relatively small energy difference, less than
0.2 eV, is obtained between the FD(0.010.4)-CASPT2 and the
standard CASPT2 results. Conversely, larger thresholds, such as
s 5 0.5, imply a dramatic decrease of the active atoms (see
Fig. 1), which leads to a significant deviation of the EVA ener-
gies from the reference values. In general, the energy differ-
ence obtained with the FD(0.010.4)-CASPT2 results can be
considered small enough for many applications of the CASPT2
method in photochemistry as the deviations are within the
accepted error of the CASSCF/CASPT2 method (around 0.20.3
eV).
Regarding the isolated thymine molecule, the present CASP-
T2(10in8)/ANO-S-VDZP/MP2/cc-pVDZ computations give rise to
the EVA values 4.98, 6.20, and 6.36 eV, for the three lowest-
Table 1. FD-CASPT2 vertical excitation energies (in eV) of deoxythymidine
using different thresholds s.
s 0.0 0.01 0.1 0.20.4
S1 4.90 5.07 5.10 5.11
S2 6.24 6.37 6.39 6.40
S3 6.27 6.42 6.47 6.47
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Table 2. Number of occupied and virtual orbitals for various FD and full
CASPT2 calculations.
FD(s)
Full 0.0 0.01 0.1 0.20.4 0.5
O 50 59 25 24 11
V 241 81 81 81 32
(xfull=x)2 1 3 35 38 1171
The quantity in the last row represents a suitable measure of the reduc-
tion in floating point operations.
lying pp* excited states, which are in agreement with previous
CASPT2 results from Schreiber et al. (4.885.06, 5.886.15, and
6.106.52 eV).[54] These energies are close to the results
obtained for the dT system, thus indicating that the nature of
the electronic excitation is determined solely by the chromo-
phore itself. Conversely, the sugar moiety is found to be crucial
for an accurate determination of the VIP in the nucleoside. In
this case, while the VIP of thymine is computed at 9.11 eV at
the CASPT2(10in8)/ANO-S-VDZP//MP2/cc-pVDZ level of theory,
in agreement with previous benchmark results,[55] a value of
8.65 is obtained for the nucleoside dT at the same level of
theory, in agreement with the experimental data (8.58 eV[56]
and 8.80 6 0.17 eV[57]. To test the applicability of the FD
approach to determine the ionization energy of dT, we have
computed the VIP energy with a threshold s 5 0.01, which
corresponds to an appropriate selection of the active region
including the whole p system. The result for the VIP of dT is
8.82 eV, which is a much better estimation as compared to the
value obtained from the thymine chromophore alone. The
deviation with respect to the VIP of dT computed with the
standard CASPT2 method are 0.17 eV at the FD-CASPT2 level,
but it is 0.46 eV when determined from full CASPT2 calcula-
tions on thymine, respectively. Thus, a deviation nearly three
times larger, and above the expected error bar of the chosen
quantum chemical method.
At the same time, the FD-CASPT2 calculation is much less
expensive than the full CASPT2 on the entire system, and not
significantly more expensive than the corresponding full
CASPT2 on the chromophore alone. In Table 2, we have
reported a measure of the reduction in floating point opera-
tions for FD-CASPT2 calculations compared to full CASPT2.
Such measure is based on the fact that the computationally
dominant steps in CASPT2 calculation (as for MP2) are quad-
ratic in the quantity x 5 O 3 V, where O and V represent the
number of occupied (inactive plus active) and virtual orbitals,
respectively. The square of the ratio between xs computed
for the full CASPT2 and for a given FD-CASPT2 measures the
reduction in floating point operations involved in the calcula-
tion, thus indicating the corresponding expected speedup in
CPU time. Clearly, FD-CASPT2 can possibly produce much
more significant speedupsup to two orders of magnitudes
0.5 for very large systemswhile retaining sufficient accuracy in
5.98 its predictions. Table 3 compiles the calculations timing in sec-
7.13 onds, which confirms the significant time reduction. Hence,
7.51
whereas 1 h and 49 min are needed for the conventional
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 REVIEW WWW.C-CHEM.ORG
Table 3. Timings (in sec) of deoxythymidine using different thresholds s.
s Timing (s)
0.0 6540
0.01 965
0.1 539
0.20.5 450
CASPT2 computations of EVA, the FD(s 5 0.20.4)-CASPT2 cal-
culations only spent 7 min and 30 sec.
Acrolein in a box of water
Solvatochromic effects on electronic excitation energies are
also a potential target of the FD-CASPT2 method, especially in
those cases where an explicit treatment of the solvent mole-
cules is desirable. The electronic excitation is usually localized
in the solute, and therefore, the surrounding solvent molecules
shall play a secondary role in the accounting for correlation
effects. The present work focuses on the analysis of the per-
formance of the FD-CASPT2 approach and, therefore, no
attempt will be made to study the details of solvent effects in
the excited states of the chosen molecule. One molecule of
acrolein surrounded by 21 water molecules has been selected
for the computation of the vertical excitation energy (EVA)
related to the lowest-lying 1(n ! p*) excited state of s-trans
acrolein. Clearly, an appropriate treatment of the solvent
would require a larger number of water molecules and a sta-
tistical description of the solvation, but for the purpose of test-
ing the reliability of FD-CASPT2 the chosen example is well-
fitting. The structure of acrolein surrounded by water mole-
cules has been optimized at the B3LYP/6-31G* level (a box of
water molecules, obtained previously in a classical dynamics
simulation with the TINKER program,[58] was used as starting
structure). Full CASPT2 calculation on the entire system would
be extremely demanding, requiring more than 22 GB of mem-
ory. Nonetheless, we can compare FD-CASPT2 results for EVA
with the corresponding energies from gas-phase calculations
and with previous experimental and theoretical values
obtained for acrolein in liquid water. Five different thresholds
have been considered for the FD scheme in the range
between 0 and 1. The active space comprises six electrons dis-
tributed in five active orbitals. It corresponds to the valence p
and p* orbitals and the oxygen lone-pair orbital. The double-f
ANO-S-VDZP basis set has been used throughout.[53] The num-
ber of selected atoms in the active region varies depending
Table 4. FD(s)-CASPT2 lowest vertical excitation energy (in eV) for acrolein in vacuo and in water solution.
Gas-phase
CASPT2 Expt. Prev. Theor.
[a] [b] [c] [d] [e] [f ]
S1(n !p*) 3.82 3.71 , 3.75 3.69 , 3.63 , 3.74 , 3.85
[a] Ref. [59], [b] Ref. [60], [c] CASPT2//CASSCF, [61], [d] CASPT2, [62], [e] MR-CISD,
CASPT2, [62].
Experimental and theoretical data from the literature are also shown.
1614 Journal of Computational Chemistry 2014, 35, 16091617
Figure 2. Molecular model of the acrolein in a water box. Atoms in orange
color are the ones assigned to the active region. a) s 5 0.10.5, b) s 5
0.01, c) s 5 0.001 blue.
on the chosen threshold. In particular, it corresponds to 16
atoms for s 5 0.001, six atoms for s 5 0.01, and four atoms
for s 5 0.1 (see Figure 2). The nonhydrogen atoms of acrolein,
which hold the excitations, plus some of the hydrogen atoms
of the solute are the only ones in the active region with the
thresholds ranging from 0.01 to 0.5, whereas some water mol-
ecules in the nearest surrounding of the solute molecule are
also considered as active for s 5 0.001.
Table 4 reports the CASPT2 energies computed both in the
gas-phase and in solution. Experimental data and previous the-
oretical values obtained with different ab initio methodologies
are also compiled for the sake of comparison. As can be seen,
deviations among the FD-CASPT2 energies obtained for the
different thresholds are very small. Such agreement is a conse-
quence of the fact that in all cases the relevant atoms are
included as active (it did not happen for dT, as shown in
Figure 1). Similar values can, thus, be expected for FD-CASPT2
computations using smaller thresholds. A good agreement is
found with the experimental data and with previous theoreti-
cal results in which the solvent effect was estimated by means
of a more accurate treatment using the averaged solvent elec-
trostatic potential from molecular dynamics[65] method or also
In water
FD-CASPT2 (s)
0.001 0.01 0.10.5 Expt. Prev. theor.
[g]
3.92 3.96 3.95 3.94 3.90[h], 3.964.06[i]
[63]
, [f ] MR-CISD-Q, [63]
, [g] Ref. [64], [h] ASEP/MD-CASPT2,[60], [i] PCM-
WWW.CHEMISTRYVIEWS.COM

Table 5. Timings (in sec) of acrolein in a box of water using different
thresholds s.
s Timing (s)
0.0
0.001
0.01
0.10.5
with the approximate polarizable continuum model (PCM)[66]
method. To compare results in gas-phase and solvent condi-
tions, the EVA of an isolated acrolein molecule was correspond-
ingly computed, using CASPT2/ANO-S-VDZP energies on top
of B3LYP/6-31G* geometries. The blue-shift for the EVA of the
1 density basically among the conjugated phenol and pyrazine
(n ! p*) state of acrolein in water, established previously
both experimentally[59,60,64] and theoretically,[6163] is repro-
duced in the present work semiquantitatively (see Table 4).
Hence, we are able to predict sizable shifts in vertical excita-
tion energies by performing relatively inexpensive CASPT2 cal-
culations on the active region only. Noticeably, variations with
respect to the definition of the active region (threshold s) are
much smaller than the physical shift sought for. With this
observation, we argue that FD-CASPT2 is indeed very robust
in accounting for the correlation effects determining such
types of physicochemical observables. Table 5 compiles the
calculations timing in second.
Coelenteramide
Another example of molecule whose quantum-chemical spec-
troscopy calculations could benefit from the FD-CASPT2
method is coelenteramide. This molecular system is responsi-
Figure 3. Molecular model of the coelenteramide molecule. Atoms in
orange color are the ones assigned to the active region. a) s 5 0.001, b) s
5 0.010.4. [Color figure can be viewed in the online issue, which is avail-
able at wileyonlinelibrary.com.]
WWW.C-CHEM.ORG REVIEW
Table 6. FD(s)-CASPT2 lowest vertical excitation energy (in eV) for
Coelentramide.
CASPT2 FD-CASPT2 (s) Expt. Prev. theor.
0.001 0.01 0.10.5
5160
S1(p !p*) 4.14 4.15 4.20 4.21 3.63.7[a] 4.27[b]
3900
3800 [a] Ref. [69], [b] Ref. [68].
Experimental and theoretical data from the literature are also shown.
ble for the light emission in the bioluminescent phenomenon
of a number of marine organisms.[67,68] As shown in the previ-
ous study by Chen et al.[68] the lowest-lying electronic transi-
tion in coelenteramide implies a redistribution of the electron
groups. Hence, we can benchmark the FD approach of the
CASPT2 method focusing in the EVA computations related to
the S0 to S1 transition.
Among the different conformational isomers plausible in
coelenteramide, we use in the present work the conformation
AI of Chen et al.[68] which was optimized at the CAM-B3LYP/6-
311G(d,p) level starting from the X-ray crystallographic struc-
ture of coelenteramide in Ca21-discharged obelin (PDB code:
2F8P.pdb). At this geometry, the EVA energies of the lowest-
lying pp* transition are computed at the FD-CASPT2 level with
different thresholds (s) and using the ANO-S-VDZP basis set.[53]
The active space comprises 12 electrons in 12 active orbitals
(12in12), including the valence p and p* orbitals of the conju-
gated phenol and pyrazine moieties. The selected active
region (region A) using different thresholds (s) in the range
0.0010.4 are displayed in Figure 3. In the example of coelen-
teramide, the s values in the FD-CASPT2 computations that
share the same region as the natural orbitals of the
CAS(12in12) space are 0.10.4. Lower s values imply the inclu-
sion as active of other atoms from the toluene and p-
hydroxyphenylacetamide groups. Computations with thresh-
olds (s) of 0.5 and larger (not shown here) has a too reduced
number of active atoms (region A) and give rise to unphysical
EVA results.
Table 6 compiles the present computed EVA values together
with previous TD-DFT results using the CAM-B3LYP functional
and the 6-311G(d,p) basis set[68] and experimental results in
DMSO and benzene solvents.[69] The FD(0.0010.4)-CASPT2
results have deviations no larger than 0.14 eV with respect to
the value obtained with the full CASPT2 method, which points
to a good performance of the FD approach as in the deoxythi-
midine and solvated acrolein systems. As can be seen in Table 6,
the CASPT2 results show a relatively good agreement with the
TD-DFT and experimental data, appearing at lower energies
Table 7. Timings (in sec) of coelenteramide using different thresholds s.
s Timing (s)
0.0 29,100
0.001 12,240
0.01 6,540
0.1 5,280
0.20.4 4,860
Journal of Computational Chemistry 2014, 35, 16091617 1615
 REVIEW WWW.C-CHEM.ORG
than the TD-DFT EVA and closer to the experimental reported
value. Regarding the timings (see Table 7), it is worth noting the
large difference of almost 7 h between the computation times
of the conventional CASPT2 and the FD(s 5 0.20.4)-CASPT2,
while the discrepancy in the EVA is only around 0.1 eV.
Conclusions
The applicability of CD-based CASSCF/CASPT2 to the study of
large molecules is hampered by two major computational bot-
tlenecks: (a) the factorial scaling of CASSCF with respect to the
size of the active space, and (b) the quartic scaling of the
number of amplitudes in the CASPT2 step. Active spaces larger
than 18 electrons in 18 orbitals (18in18) are at present beyond
reach. To overcome this limit, the so-called RASSCF/RASPT2
method,[5,7072] or the recently proposed SplitCAS/SplitGAS
approach[73,74] can be used to map the CAS eigenvalue prob-
lem to a much smaller dimensionality. In all situations where
the active space bottleneck is avoided, it remains to cope with
the cost of determining the amplitudes for the CASPT2 correc-
tion. This is particularly problematic for large molecules and
accurate AO basis sets.
In this work, we have demonstrated the benefits arising from
the use of a localized orbital picture in CD-based CASPT2 calcu-
lations on large molecules. For situations where the active orbi-
tals are localized within a small region of the molecule, a
suitable active site can be identified as the collection of atoms
where the active orbitals effectively extend. Accordingly, the
inactive and secondary orbitals can be separately localized and
partitioned between this active site and the remaining atoms
(environment). The two regions are assumed to be uncoupled,
and therefore, two separate sets of canonical orbitals can be
deduced for the active site and the environment. In this way,
the standard algorithm for CASPT2 can be used without the
need to reformulate the method in noncanonical orbital basis.
In terms of its implementation, the method is equivalent to an
appropriate removal of some orbitals from the inactive and sec-
ondary space, hence the name freeze-and-delete (FD) CASPT2.
The performance of the FD approach has been analyzed
through three illustrative examples of CASPT2 energy compu-
tations: the three lowest-energy vertical electronic transitions
and the lowest VIP of the deoxythymidine nucleoside, the ver-
tical 1(n ! p*) transition of acrolein surrounded by water mol-
ecules, and the lowest-energy vertical 1(p ! p*) transition of
coelenteramide. It is shown that accurate relative energies
(within 0.2 eV) can be computed by performing FD-CASPT2
calculations in which the correlating orbitals are restricted to
only those assigned to the active site. This allows for substan-
tial savings in storage demand and computational costsnot
uncommonly, of 12 orders of magnitude. However, it has to
be pointed out that the accuracy of the FD approach is 510
times lower than those observed for local time dependent
second-order coupled cluster model (TD-CC2)[75] methods over
a large range of different molecules and excitations. Moreover,
the portion of correlation energy associated with the environ-
ment is estimated at the cost of a canonical MP2-type energy
calculation. Given that the static correlation effects are taken
1616 Journal of Computational Chemistry 2014, 35, 16091617
into account for the whole system at the CASSCF level of
theory, this methodology can be considered as a two-scale
hierarchical approach to the electron correlation problem.
Acknowledgment
rn Roos, who unfortu-
This work was initiated by late Prof. Bjo
nately could not see the final outcome of his idea.
Keywords: multiconfigurational perturbation theory  correlation
energy  excited states  deoxythymidine  acrolein  coelenteramide
How to cite this article: P. Farahani, D. Roca-Sanjuan, Aquilante,
F. J. Comput. Chem. 2014, 35, 16091617. DOI: 10.1002/
jcc.23666
[1] D. Roca-Sanjuan, F. Aquilante, R. Lindh, WIREs Comput. Mol. Sci. 2012,
2, 585.
[2] K. Andersson, B. O. Roos, In Modern Electron Structure Theory, Vol. 2,
Part I; R. Yarkony, Ed.; World Scientific Publishing: Singapore, 1995; pp.
55109.
[3] F. Aquilante, P.-A. Malmqvist, T. B. Pedersen, A. Ghosh, B. O. Roos, J.
Chem. Theory Comput. 2008, 4, 694.
[4] F. Aquilante, T. B. Pedersen, B. O. Roos, A. Sanchez de Meras, H. Koch,
J. Chem. Phys. 2008, 129, 24113.
[5] S. M. Huber, M. Z. Ertem, F. Aquilante, L. Gagliardi, W. B. Tolman, C. J.
Cramer, Chem. Eur. J. 2009, 15, 4886.
[6] K. Pierloot, S. Vancoillie, J. Chem. Phys. 2008, 128, 34104.
[7] G. L. Macchia, F. Aquilante, V. Veryazov, B. O. Roos, L. Gagliardi, Inorg.
Chem. 2008, 47, 11455.
[8] N. H. F. Beebe, J. Linderberg, Int. J. Quantum Chem. 1977, 7, 683.
[9] H. Koch, A. Sanchez de Meras, T. B. Pedersen, J. Chem. Phys. 2003, 118,
9481.
[10] F. Aquilante, R. Lindh, T. B. Pedersen, J. Chem. Phys. 2007, 127, 114107.
[11] F. Aquilante, R. Lindh, T. B. Pedersen, J. Chem. Phys. 2008, 129, 34106.
[12] F. Aquilante, T. B. Pedersen, L. Gagliardi, R. Lindh, J. Chem. Phys. 2009,
130, 154107.
[13] J. Bostrom, F. Aquilante, T. B. Pedersen, R. Lindh, J. Chem. Theory Com-
put. 2009, 5, 1545.
[14] J. Bostrom, M. Delcey, F. Aquilante, T. B. Pedersen, L. Serrano-Andr es,
R. Lindh, J. Chem. Theory Comput. 2010, 6, 747.
[15] T. B. Pedersen, F. Aquilante, R. Lindh, Theor. Chem. Acc. 2009, 124, 1.
[16] F. Aquilante, L. Boman, J. Bostr om, H. Koch, T. B. Pedersen, A. S. de
Meras, R. Lindh, In Challenges and Advances in Computational Chem-
istry and Physics, Vol. 13; M. G. Papadopoulos, R. Zalesny, P. G. Mezey,
J. Leszczynski, Eds.; Springer, London, 2011; pp. 301344.
[17] F. Aquilante, T. B. Pedersen, R. Lindh, J. Chem. Phys. 2007, 126, 194106.
[18] F. Aquilante, T. B. Pedersen, A. Sanchez de Meras, H. Koch, J. Chem.
Phys. 2006, 125, 174101.
[19] F. Aquilante, T. K. Todorova, T. B. Pedersen, L. Gagliardi, B. O. Roos, J.
Chem. Phys. 2009, 131, 34113.
[20] G. La Macchia, G. Li Manni, T. K. Todorova, M. Brynda, F. Aquilante, B.
O. Roos, L. Gagliardi, Inorg. Chem. 2010, 49, 5216.
[21] P. Surjan, D. Kohalmi, Z. Rolik, A. Szabados, Chem. Phys. Lett. 2008,
450, 400.
[22] N. Govind, Y. A. Wang, A. J. R. da Silva, E. A. Carter, Chem. Phys. Lett.
1998, 295, 129.
[23] T. A. Wesolowski, Computational Chemistry: Reviews of Current
Trends, Vol. 10; World Scientific, Singapore, 2006, 10, 1.
[24] T. A. Wesolowski, A. Warshel, J. Phys. Chem. 1993, 97, 8050.
[25] C. R. Jacob, L. Visscher, In Recent Advances in Orbital-Free Density
Functional Theory; T. A. Wesolowski, Y. A. Wang, Eds.; World Scientific,
Singapore, 2013, 6, 297.
[26] S. Dapprich, I. Komaromi, K. S. Byun, K. Morokuma, M. J. Frisch, J. Mol.
Struct. (Theochem) 1999, 461, 1.
WWW.CHEMISTRYVIEWS.COM
 WWW.C-CHEM.ORG
[27] T. Korona, D. Kats, M. Sch utz, T. B. Adler, Y. Liu, H. J. Werner, Chal-
lenges and Advances in Computational Chemistry and Physics, Vol. 13;
Springer, London, 2011; pp. 345407.
[28] T. D. Crawford, R. A. King, Chem. Phys. Lett. 2002, 366, 611.
[29] R. A. Mata, H. J. Werner, M. Sch utz, J. Chem. Phys. 2008, 128, 144106.
[30] D. Kats, M. Sch utz, J. Chem. Phys. 2009, 131, 124117.
[31] R. A. Mata, H. Stoll, J. Chem. Phys. 2011, 134, 034122.
[32] T. S. Chwee, E. A. Carter, J. Chem. Theory Comput. 2011, 103, 7.
[33] G. Walz, D. Kats, D. Usvyat, T. Korona, M. Sch utz, Phys. Rev. A 2012, 86,
052519.
[34] P. Pulay, Chem. Phys. Lett. 1983, 100, 151.
[35] M. Sch utz, G. Hetzer, H. J. Werner, J. Chem. Phys. 1999, 111, 5691.
[36] J. M. Foster, S. F. Boys, Rev. Mod. Phys. 1960, 32, 300.
[37] J. Pipek, P. G. Mezey, J. Chem. Phys. 1989, 90, 4916.
[38] C. Hampel, H. J. Werner, J. Chem. Phys. 1996, 104, 6286.
[39] S. Saebo, P. Pulay, Annu. Rev. Phys. Chem. 1993, 44, 213.
[40] J. W. Boughton, P. Pulay, J. Comput. Chem. 1993, 14, 736.
[41] M. Sch utz, H. J. Werner, J. Chem. Phys. 2001, 114, 661.
[42] H. J. Werner, F. R. Manby, P. J. Knowles, J. Chem. Phys. 2003, 118, 8149.
[43] P.-A. Malmqvist, K. Pierloot, A. R. M. Shahi, C. J. Cramer, L. Gagliardi, J.
Chem. Phys. 2008, 128, 204109.
[44] F. Aquilante, T. B. Pedersen, Chem. Phys. Lett. 2007, 449, 354.
[45] O. Masur, D. Usvyat, M. Sch utz, J. Chem. Phys. 2013, 139, 164116.
[46] F. Aquilante, L. D. Vico, N. Ferr e, G. Ghigo, P.-A. Malmqvist, P. Neogrady,
T. B. Pedersen, M. Pito nak, M. Reiher, B. O. Roos, L. Serrano-Andr es, M.
Urban, V. Veryazov, R. Lindh, J. Comput. Chem. 2010, 31, 224.
[47] F. Ruiperez, F. Aquilante, J. M. Ugalde, I. Infante, J. Chem. Theory Com-
put. 2011, 7, 1640.
[48] G. Ghigo, B. O. Roos, P.-A Malmqvist, Chem. Phys. Lett. 2004, 396, 142.
[49] M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria, M. A. Robb, J. R.
Cheeseman, G. Scalmani, V. Barone, B. Mennucci, G. A. Petersson, H.
Nakatsuji, M. Caricato, X. Li, H. P. Hratchian, A. F. Izmaylov, J. Bloino, G.
Zheng, J. L. Sonnenberg, M. Hada, M. Ehara, K. Toyota, R. Fukuda, J.
Hasegawa, M. Ishida, T. Nakajima, Y. Honda, O. Kitao, H. Nakai, T. Vreven,
J. A. Montgomery, J. E. Peralta, F. Ogliaro, M. Bearpark, J. J. Heyd, E.
Brothers, K. N. Kudin, V. N. Staroverov, R. Kobayashi, J. Normand, K.
Raghavachari, A. Rendell, J. C. Burant, S. S. Iyengar, J. Tomasi, M. Cossi, N.
Rega, J. M. Millam, M. Klene, J. E. Knox, J. B. Cross, V. Bakken, C. Adamo,
J. Jaramillo, R. Gomperts, R. E. Stratmann, O. Yazyev, A. J. Austin, R.
Cammi, C. Pomelli, J. W. Ochterski, R. L. Martin, K. Morokuma, V. G.
Zakrzewski, G. A. Voth, P. Salvador, J. J. Dannenberg, S. Dapprich, A. D.
Farkas, J. B. Foresman, J. V. Ortiz, J. Cioslowski, D. J. Fox, Gaus-
Daniels, O.
sian, Inc., Wallingford CT, 2009.
[50] M. Rubio, D. Roca-Sanjuan, M. Merchan, L. Serrano-Andr es, J. Phys.
Chem. B 2006, 110, 10234.
REVIEW
[51] M. Rubio, D. Roca-Sanjuan, L. Serrano-Andr es, M. Merchan, J. Phys.
Chem. B 2009, 113, 2451.
[52] R. Improta, V. Barone, Theor. Chim. Acta 2008, 120, 491.
[53] K. Pierloot, B. Dumez, P. O. Widmark, B. O. Roos, Theor. Chim. Acta
1995, 90, 87.
[54] M. Schreiber, M. R. Silva-Junior, S. P. Sauer, W. Thiel, J. Chem. Phys.
2008, 128, 134110.
[55] D. Roca-Sanjuan, M. Rubio, M. Merchan, L. Serrano-Andr es, J. Chem.
Phys. 2006, 125, 084302.
[56] C. Yu, T. J. ODonnell, P. R. LeBreton, J. Phys. Chem. 1981, 85, 3851.
[57] S. Ptasinska, P. Candori, S. Denifl, S. Yoon, V. Grill, P. Scheier, T. D. Mark,
Chem. Phys. Lett. 2005, 409, 270.
[58] J. Ponder, F. M. Richards, J. Comput. Chem. 1987, 8, 1016.
[59] R. S. Becker, K. Inuzuka, J. King, J. Chem. Phys. 1970, 52, 5164.
[60] A. D. Walsh, Trans. Faraday Soc. 1945, 41, 498505.
[61] M. E. Martin, A. M. Losa, I. Fernandez-Galvan, M. A. Aguilar, J. Chem.
Phys. 2004, 121, 3710.
[62] F. Aquilante, V. Barone, B. O. Roos, J. Chem. Phys. 2003, 119, 12323.
[63] S. A. do Monte, T. M uller, M. Dallos, H. Lischka, M. Diedenhofen, A.
Klamt, Theor. Chem. Acc. 2004, 111, 78.
[64] A. E. Moskvin, O. P. Yablonskii, L. F. Bondar, Theor. Exp. Chem. 1966, 2, 469.
[65] I. F. Galvan, M. L. Sanchez, M. E. Martn, F. J. O. del Valle, M. A. Aguilar,
Comput. Phys. Commun. 2003, 155, 244.
[66] J. Tomasi, B. Mennucci, R. Cammi, Chem. Rev. 2005, 105, 2999.
[67] D. Roca-Sanjuan, M. G. Delcey, I. Navizet, N. Ferr e, Y.-J. Liu, R. Lindh, J.
Chem. Theory Comput. 2011, 7, 4060.
[68] S. F. Chen, I. Navizet, D. Roca-Sanjuan, R. Lindh, Y.-J. Liu, N. Ferr e, J.
Chem. Theory Comput. 2012, 8, 2796.
[69] O. Shimomora, K. Teranishi, Luminescence 2000, 15, 51.
[70] S. M. Huber, A. R. M. Shahi, F. Aquilante, C. J. Cramer, L. Gagliardi, J.
Chem. Theory Comput. 2009, 5, 2967.
[71] P.-A. Malmqvist, K. Pierloot, A. R. M. Shahi, C. J. Cramer, L. Gagliardi, J.
Chem. Phys. 2008, 128, 2041092.
[72] A. R. M. Shahi, C. J. Cramer, L. Gagliardi, Phys. Chem. Chem. Phys.
2009, 11, 10964.
[73] G. L. Manni, F. Aquilante, L. Gagliardi, J. Chem. Phys. 2011, 134, 34114.
[74] G. L. Manni, D. Ma, F. Aquilante, J. Olsen, L. Gagliardi, J. Chem. Theory
Comput. 2013, 9, 3375.
[75] K. Lederm uller, M. Schutz, J. Chem. Phys. 2014, 140, 164113.
Received: 14 January 2014
Revised: 3 June 2014
Accepted: 6 June 2014
Published online on 7 July 2014
Journal of Computational Chemistry 2014, 35, 16091617 1617