1. SPECIAL FEATURE
Investigation of metal– dithiolate fold angle effects:
Implications for molybdenum and tungsten enzymes
Hemant K. Joshi, J. Jon A. Cooney, Frank E. Inscore, Nadine E. Gruhn, Dennis L. Lichtenberger†, and John H. Enemark†
Department of Chemistry, University of Arizona, Tucson, AZ 85721
Edited by Jack Halpern, University of Chicago, Chicago, IL, and approved January 31, 2003 (received for review November 8, 2002)
Gas-phase photoelectron spectroscopy and density functional the d orbital in the equatorial plane being empty, whereas for
theory have been used to investigate the interactions between (Tp*)MoO(bdt) this d orbital is half-filled (11). The larger
the sulfur -orbitals of arene dithiolates and high-valent transi- fold angle for (Tp*)Mo(NO)(bdt) has been ascribed to a sta-
tion metals as minimum molecular models of the active site fea- bilizing interaction of the filled p orbitals on sulfur with the
tures of pyranopterin Mo W enzymes. The compounds empty metal orbital in the equatorial plane on bending (11),
(Tp*)MoO(bdt) (compound 1), Cp2Mo(bdt) (compound 2), and which is illustrated schematically in Fig. 2. For other reported
Cp2Ti(bdt) (compound 3) [where Tp* is hydrotris(3,5-dimethyl-1- (Tp*)Mo(NO)(dithiolate) compounds, the fold angle is always
pyrazolyl)borate, bdt is 1,2-benzenedithiolate, and Cp is 5- 40–45° and is essentially independent of the electron-donating
cyclopentadienyl] provide access to three different electronic or electron-withdrawing nature of substituents on the dithio-
configurations of the metal, formally d1, d2, and d0, respectively. late ligand (11). In contrast, for (Tp*)MoO(dithiolate) com-
The gas-phase photoelectron spectra show that ionizations from plexes the fold angle ranges from 6.9° in (Tp*)MoO(bdtCl2)
occupied metal and sulfur based valence orbitals are more (14) to 29.5° in (Tp*)MoO(qdt) (11), suggesting a much shal-
clearly observed in compounds 2 and 3 than in compound 1. lower potential surface for the interaction of the filled sul-
The observed ionization energies and characters compare very fur-p (S ) orbitals with the half-filled equatorial metal or-
CHEMISTRY
well with those calculated by density functional theory. A bital (metal in-plane or Mip). For comparison, the calculated
‘‘dithiolate-folding-effect’’ involving an interaction of the metal fold angles for dithiolates in protein structures (Table 1)
in-plane and sulfur- orbitals is proposed to be a factor in the range from 7–30° (5, 15–17).
electron transfer reactions that regenerate the active sites of The (Tp*)MoO(dithiolate) compounds have also been in-
molybdenum and tungsten enzymes. vestigated by a variety of spectroscopic techniques, including
EPR (12, 13), electronic absorption, resonance Raman, and
magnetic CD spectroscopies (10, 18, 19). The general conclu-
C oordination by the sulfur atoms of one or two ene-1,2-
dithiolate (dithiolene) ligands of the novel substituted
pyranopterin-dithiolate (‘‘molybdopterin’’; ref. 1) is a common
sion from these studies is that the singly occupied molecular
orbital in these formally d1 centers has substantial sulfur char-
structural feature of mononuclear molybdenum-containing acter (10, 18, 19). From these studies it was proposed that
enzymes (2–4). These enzymes catalyze a wide range of oxi- pseudo- interactions between the in-plane metal orbital and
dation reduction reactions in carbon, sulfur, and nitrogen me- sulfur in-plane lone pairs play an important role in electron
tabolism. Fig. 1 shows the structure of the active site of sulfite transfer reactions that regenerate the active sites of enzymes
oxidase, a representative example (5, 6) of the coordination (10). However, Fig. 2 suggests that sulfur out-of-plane orbitals
of the pyranopterin-dithiolate (hereafter abbreviated S2pdt; could also have a major effect on these processes. To date,
ref. 7). These structural results raise fundamental questions the role of fold angle on metal–sulfur interactions has not
about the role of the S2pdt coordination in the overall cata- been quantitatively assessed.
lytic cycle of molybdenum enzymes (8). The unusual ability of A technique capable of assessing the metal and ligand char-
ene-1,2-dithiolate ligands to stabilize metals in multiple oxida- acter of orbitals is gas-phase photoelectron spectroscopy
tion states has been recognized since the compounds were using ionization sources with different photon energies (20).
first investigated (9). Proposed roles for the S2pdt ligand in- Previously we have reported photoelectron spectra for
clude functioning as an electron transfer conduit from the (Tp*)MoE(tdt) (where E O, S, or NO, and tdt is 3,4-
metal to other prosthetic groups (10) and as a modulator of toluenedithiolate) by using HeI, HeII and NeI photon
the oxidation reduction potential of the metal site (10). Dur- sources that indicate strong mixing between Mo and S or-
ing catalysis, the metal center is proposed to pass through the bitals (21). Interestingly, the first ionization energies of
M(VI V IV) oxidation states, i.e., the Mo d electron count (Tp*)Mo(NO)(tdt), a formally d4 metal center, and
changes from d0 to d1 to d2. Thus, studies of discrete metal (Tp*)MoO(tdt), a formally d1 metal center, differ by only
dithiolate complexes encompassing these and related electron 0.05 eV, despite the variation in axial ligand and total number
configurations may provide insight concerning metal thiolate of metal d electrons. This similarity in ionization energies was
bonding and reactivity in enzymes. ascribed to the ‘‘electronic buffer effect’’ of the dithiolate li-
Previous structural studies of model molybdenum com- gand (21). Subsequent photoelectron spectroscopic studies of
plexes of the type (Tp*)MoE(1,2-dithiolate) [where E is O or other pairs of (Tp*)MoE(dithiolate) complexes (E O, NO)
NO, Tp* is hydrotris(3,5-dimethyl-1-pyrazolyl)borate, and the have shown that the first ionization energies of the members
1,2-dithiolates are bdt (1,2-benzenedithiolate), bdtCl2 (3,6- of each pair are within 0.2 eV of one another. For a series
of (Tp*)MoO(dithiolate) complexes with varying peripheral
dichlorobenzenedithiolate), and qdt (2,3-quinoxalinedithio-
late)] have shown that the fold angle of the dithiolate metal-
lacycle along the S S vector (Fig. 2) varies in a way that This paper was submitted directly (Track II) to the PNAS office.
depends on the occupation of a d orbital that is in the equa- Abbreviations: HOMO, highest occupied molecular orbital; SCF, self-consistent field.
torial plane (11). For (Tp*)MoO(bdt), which has a formal 4d1
Data deposition: The atomic coordinates for 2 have been deposited in the Cambridge
electron configuration, the fold angle is 21.3° (12, 13). How- Structural Database, Cambridge Crystallographic Data Centre, Cambridge CB2 1EZ, United
ever, for (Tp*)Mo(NO)(bdt), the fold angle is 41.1° (11). Al- Kingdom (CSD reference no. 201539).
though the metal center of (Tp*)Mo(NO)(bdt) is formally d4, †To whom correspondence may be addressed. E-mail: dlichten@u.arizona.edu or
the strong -acceptor character of the NO ligand results in jenemark@u.arizona.edu.
www.pnas.org cgi doi 10.1073 pnas.0636832100 PNAS April 1, 2003 vol. 100 no. 7 3719 –3724

2. Table 1. Fold angles measured for the dithiolate unit in
structurally characterized representative pyranopterin
Mo enzymes
Enzyme Resolution, Å Fold angle, ° Ref.
Sulfite oxidase 1.9 6.6 and 7.0 5
Aldehyde oxidoreductase 1.28 16.6 15
(MOP) (oxidized)
Xanthine dehydrogenase 2.1 20.1 and 14.3 16
Dimethyl sulfoxide reductase 1.3 18.2 and 33.1 17
(oxidized)
For the (Tp*)MoO(dithiolate) molecules that we have previ-
ously studied there is also a metal-d orbital in the equatorial
Fig. 1. The active site of chicken liver sulfite oxidase illustrating a pyranop- plane with respect to the dithiolate ligand that is, in this case,
terin dithiolate appended to the Mo center (5). half-occupied for the d1 [Mo(V)] electron configuration.
Fourmigue and coworkers (26, 30, 31) have studied
´
Cp2M(dithiolate) and [CpM(dithiolate)2] 1,0 in the context of
substitutions on the dithiolate ligand, the first ionization ener- novel molecular materials. They have found that the d0 com-
gies show a range of 0.7 eV and correlate with the lowest pounds, Cp2Ti(dithiolate), have large fold angles (e.g., 46.0°
energy oxidation potential in solution (11, 22). Gas-phase for Cp2Ti(bdt); ref. 26) in the solid state. The barrier to inter-
photoelectron spectroscopy avoids possible complications of conversion between the positive and negative extremes of fold
solvent and solid state effects, but a major drawback is that angle in solution has been determined by NMR to be 14
only neutral species are easily studied by this technique, and kcal mol 1 (25, 30), close to the computed value of 15
the (Tp*)MoO(dithiolate) system does not allow access to the kcal mol 1 (31). The observed folding for the Ti d0 systems
important d0 and d2 electron configurations of the catalytic could facilitate interaction of the filled S orbitals with the
cycle. Additional analysis of the molybdenum-dithiolate inter- empty Mip orbital, similar to the diagram shown in Fig. 2. In
action in the photoelectron spectra of (Tp*)MoO(dithiolate) contrast, for the d2 metal system, Cp2Mo(bdt), the fold angle
is also difficult because the broad area of ionizations from the in the solid state is 9.0° (32). Fourmigue et al. (33) have
´
Tp* ligand is not well separated from the region containing found that the oxidation potentials of Cp2M(dithiolate) com-
Mo 4d and S 3p ionizations (11, 14, 21, 23). A third potential pounds are not significantly different for M Mo and W,
complication of interpretation of photoelectron spectra of suggesting that the highest occupied molecular orbital
(Tp*)MoO(dithiolate) complexes is the formation of both sin- (HOMO) has substantial sulfur character. Pilato et al. (34)
glet and triplet states from ionization of such a d1 system, have prepared Cp2Mo(dithiolate) compounds in which the
though we have seen no indication that this is a problem (24). dithiolate contains an appended pterin group as mimics for
Thus, we have further sought a simple system that can pro- pyranopterin-dithiolate centers. Molecular orbital calculations
vide experimental gas-phase photoelectron data for formally and EPR data for [Cp2Mo(dithiolate)] cations indicate that
d0 and d2 metal dithiolate complexes and which is amenable the HOMO is significantly ligand based (33–38). A study of
to density functional theory calculations with a minimum of ( 5-tBuC5H4)2Zr(Se2C6H4) (39) demonstrated that these sys-
simplifying assumptions. tems are amenable to gas-phase photoelectron spectroscopy.
The known bent-metallocene dithiolate compounds To our knowledge, however, there has been no detailed
[Cp2M(dithiolate), M Ti, Mo and Cp is 5-cyclopentadi- investigation of the gas-phase photoelectron spectra of
enyl] provide access to d0 (Ti) and d2 (Mo) electron configu- Cp2Mo(dithiolate) compounds to experimentally probe the
rations (25, 26). A general bonding description of Cp2MX2 molybdenum and sulfur character in the occupied valence
compounds is well understood (27–29), and Lauher and Hoff- orbitals of these systems to assess whether the valence
mann (27) first explained that the variation in fold angle for molecular orbitals are primarily metal, primarily sulfur, or
Cp2M(dithiolate) compounds is caused by the occupancy of strongly mixed. Here we present gas-phase PES data for
the metal d orbital in the equatorial plane (Mip) with respect (Tp*)MoO(bdt) (1) and Cp2M(bdt) [M Mo (2), Ti (3)].
to the dithiolate ligand. This orbital is empty for the folded d0 The analysis of the experimental data are aided by density
(Ti) case and filled for the more nearly planar d2 (Mo) case. functional theory calculations on the neutral ground state
of the molecules 1-3, and the ion states formed by photo-
ionization.
Materials and Methods
Synthesis of Compounds. The compounds (Tp*)MoO(bdt) (12),
Cp2Mo(bdt) (32), and Cp2Ti(bdt) (40, 41) were synthesized
according to published procedures and under anaerobic con-
ditions by using either an inert atmosphere glove bag or stan-
dard Schlenk line techniques. The modified synthesis of
Cp2Mo(bdt) involved a 1:3 mixture of water and organic sol-
vent to give better yield of the final product. Electronic ab-
sorption (1,2-dichloroethane solutions on a modified Cary 14
with OLIS interface, 250–900 nm), EPR (frozen glasses at 77
K, in dry degassed toluene, at 9.1 GHz with a Bruker ESP
Fig. 2. The bonding interaction of the symmetric combination (S ) of sulfur
300) and infrared (KBr disks on a Nicolet Avatar ESP Fou-
out-of-plane orbitals with the metal in-plane d orbital on folding of the
dithiolate along the S S vector indicated by the line.
rier transform infrared, 4,000–400 cm 1) spectroscopies and
3720 www.pnas.org cgi doi 10.1073 pnas.0636832100 Joshi et al.

3. SPECIAL FEATURE
Fig. 3. Gas-phase photoelectron spectra of (Tp*)MoO(bdt) (1), Cp2Mo(bdt) (2), and Cp2Ti(bdt) (3) with HeI and HeII excitation.
mass spectrometry (FAB ionization in a 3-nitrobenzyl alcohol polarization function for all elements besides Mo. Calcula-
CHEMISTRY
matrix on a JEOL HX110) were used to identify the tions on the ground-state molecules were performed in the
compounds. spin-restricted mode. Spin-unrestricted calculations were per-
formed on the relevant ion states at the fixed geometry of the
Photoelectron Spectroscopy. Photoelectron spectra were re- neutral molecule (Table 7, which is published as supporting
corded by using an instrument, procedures and calibration information on the PNAS web site). The difference between
that have been described in more detail (21). During data the total self-consistent field (SCF) energy of the ion and the
collection, the instrument resolution (measured by using full- total SCF energy of the neutral ground state is the SCF es-
width half maximum of the argon 2P3/2 peak) was 0.020–0.030 timate of the ionization energy. A linear correction was ap-
eV. The sublimation temperatures were (10 4 Torr, moni- plied for comparison of the calculated and the observed ener-
tored by using a ‘‘K’’ type thermocouple passed through a gies, i.e., calculated SCF energies were shifted by the
vacuum feedthrough and attached directly to the sample cell) difference between the experimentally obtained and the cal-
195–205°C for compound 1, 190–200°C for compound 2, and culated first ionization energies. Similarly, orbital energy esti-
175–185°C for compound 3. mates of the ionization energies were shifted by the differ-
In the figures the vertical length of each data mark repre- ence between the observed first ionization energy and the
sents the experimental variance of that point. The valence negative of the calculated eigenvalue of the HOMO.
ionization bands are represented analytically with the best fit
of asymmetric Gaussian peaks (42). The number of peaks Results and Discussion
used in a fit was based solely on the features of a given band Photoelectron Spectra. The low energy valence regions of the
profile. The peak positions are reproducible to about 0.02 gas-phase photoelectron spectra of 1-3 collected with both
eV ( 3 ). The parameters describing an individual Gaussian HeI and HeII photon sources are presented in Fig. 3. This
peak are less certain when two or more peaks are close in energy region contains the ionizations that correspond to re-
energy and overlap. moval of electrons from the first two or three occupied mo-
lecular orbitals of these molecules. For the Ti-containing mol-
Theoretical Methods. The Amsterdam density functional theory ecule (3), the spectra contain two ionizations that correspond
package (ADF 2000.01) was used to study the electronic to removal of electrons from the symmetric and antisymmet-
structures of the compounds 1–3 (43–47). The optimized ge- ric (bands S and S , respectively) combinations of sulfur-
ometry of 1 (Table 3, which is published as supporting infor- orbital (S ) orbitals. For the Mo-containing molecules (1 and
mation on the PNAS web site, www.pnas.org) was obtained 2), an additional ionization is observed in this region that cor-
beginning from the crystal structure geometry (Table 4, which responds to removal of an electron from the half (1) or fully
is published as supporting information on the PNAS web site) (2) occupied equatorial metal d orbital. The specific assign-
(13), and optimized geometries of 2 and 3 (Tables 5 and 6, ment of the ionizations can be made by comparison of the
which are published as supporting information on the PNAS spectra to those of related molecules and by comparison of
web site) were obtained beginning from geometric coordi- the relative ionization intensities as the source energy is var-
nates of a biscyclopentadienyl metal dithiolate system with a ied (21). From previous experimental studies (20, 50) and cal-
ligand fold angle of 1.2° and in C1 symmetry. The 3,5-di- culations of atomic photoionization cross-sections (51), it is
methyl groups on Tp* were replaced by hydrogen atoms (Tp expected that ionizations from orbitals with significant Ti 3d
ligand) to simplify the computations. A generalized gradient or Mo 4d contributions will increase in intensity compared
approximation, with the exchange correction of Becke (48) with ionizations of primarily S 3p character when data col-
and the correlation correction of Lee et al. (49), was used for lected with a HeII photon source is compared with data col-
all density functional calculations. Core levels (up to 3d for lected with a HeI photon source. Mixing of metal and sulfur
Mo, up to 1s for C, N, O, and S) were treated as frozen orbit- character in orbitals will result in smaller changes in relative
als. No core levels for Ti were treated as frozen. The calcula- intensities of ionizations being observed.
tions used triple- basis sets with Slater type orbitals and a For molecule 1, the lowest energy ionization band (labeled
Joshi et al. PNAS April 1, 2003 vol. 100 no. 7 3721

4. Table 2. Experimental and calculated SCF and orbital ionization energies (eV) for the ionizations from sulfur antisymmetric (S ),
sulfur symmetric (S ), and metal in-plane (Mip) orbitals of 1–3
(Tp*)MoO(bdt) (1) Cp2Mo(bdt) (2) Cp2Ti(bdt) (3)
PES Orbital PES Orbital PES Orbital
Compound method (assignment) SCF† energy† (assignment) SCF energy (assignment) SCF energy
First ionization 7.04 (Mip) 7.04 (6.51) 7.04 (4.35) 6.29 (S ) 6.29 (6.46) 6.29 (3.96) 7.18 (S ) 7.18 (6.67) 7.18 (4.58)
Second ionization 7.54 (S ) S 7.49 7.60 7.04 (Mip) 6.75 6.58 7.43 (S ) 7.37 7.36
T 7.20
Third ionization 7.71 (S ) S 7.53 7.85 7.24 (S ) 6.94 6.93 — — —
T 7.47‡
Onset of further ionizations 8.23 Did not converge 8.52 8.32 8.07 7.99 8.19 8.12 8.16
PES, experimental vertical ionization; orbital energy, negative of the orbital eigenvalue; S, singlet; T, triplet; SOMO, smallest occupied molecular orbit. SCF
ionization energies and orbital energies have been shifted so that first SCF ionization energy and highest occupied orbital energy agree with the experimental
first ionization energy. Values in parentheses are unshifted values of the HOMO SOMO for SCF, and the negative of the orbital eigenvalue of the HOMO SOMO
for orbital energy.
†The methyl groups of the Tp* ligand were replaced with H atoms to simplify calculations.
‡SCF converged to three decimal places.
Mip in Fig. 3) at 7.04 eV is similar in appearance to the low S Mip S ionizations in HeI photon source is 1.00:1.03:0.82;
energy band of related complexes having alkoxide ligands (23, that in HeII is 1.00:1.39:0.67. The energy of the metal based
52) that has been assigned to ionization arising primarily from ionization (Mip) in 1 and 2 stays constant (at 7.04 eV) despite
the half-filled metal-based orbital (21, 23, 52). The two ion- significant perturbations in the first coordination sphere and
izations between 7.25 eV to 8.00 eV can then be assigned to formal oxidation state of the metal.
ionizations associated with symmetric (S ) and antisymmetric
(S ) combinations of S orbitals based on previous assign- Computational Results. The electronic structures of 1–3 were
ment of analogous complexes (21, 22). More detailed assign- calculated by using C1 symmetry and geometry optimized mo-
ment of the S and S ionizations is not possible because of lecular structures. The geometry optimizations are carried out
the significant overlap of these low-energy features and the on isolated molecules (45), corresponding to the conditions of
beginning of the Tp* ligand based ionizations. The ratio of the PES experiment. These molecular structures compare well
the areas of the Mip ionization and the sum of the overlap- with the reported structures determined from x-ray crystallog-
ping S and S ionizations changes very little with change in raphy (Tables 8 and 9, which are published as supporting in-
photon source from HeI to HeII; the Mip (S S ) ratio in formation on the PNAS web site). As a result of geometry
HeI is 0.66:1.00, that in HeII is 0.63:1.00. The observation of optimization, the dithiolate fold angle changes from the crys-
only small changes in the relative intensities of the first three tallographic fold angle of 21.3° (12) to 31.0° in 1, from 9.0°
bands with ionization source energy was suggested to be evi- (32) to 4.8° in 2, and from 46.0° (53) to 41.6° in 3.
dence of substantial mixing of metal and sulfur character in Density functional theory calculations provide additional
(Tp*)MoO(tdt) (21). insight into the metal–dithiolate interactions and indicate
The photoelectron spectra of the Ti molecule (3) show two that, on dithiolate folding, the mixing of metal d and sulfur
overlapping ionization bands at 7.18 eV and 7.43 eV that p orbitals can be favored by their energy and symmetry
must contain contributions from the S and S ionizations. match. The energies and general characters of the ionizations
The ratio of the areas of the low-energy band to the high- observed for molecules 1-3 by photoelectron spectroscopy
energy band increases significantly with change in photon match those calculated by the SCF method and by compari-
source from HeI to HeII. The ratio in HeI is 1.00:1.02; that son of orbital energies (Table 2 and Table 10, which is pub-
in HeII is 1.00:0.37. This behavior is consistent with the lower lished as supporting information on the PNAS web site). The
energy peak containing contributions from Ti. Therefore, the calculated orbital energies for 2 are low in comparison to the
lower energy peak is assigned to S , which has the proper experimental values. This appears to be a function of the fold
symmetry to interact with the empty metal orbital on folding. angle. Fig. 4 shows a Walsh diagram for the variation of the
The higher energy peak in 3 is assigned to the S ionization, orbital eigenvalues for 2 with fold angle. The S eigenvalue
which does not mix significantly with the empty Ti d acceptor becomes less negative and Mip becomes more negative with
orbital (discussed later in the calculations section). The sym- increasing fold angle. The S eigenvalue and the onset of fur-
metric combination of the sulfur orbitals (S ) is more desta- ther ionizations remain relatively constant. The angle at
bilized than the antisymmetric combination (S ) because of which the orbital eigenvalues most closely resemble that de-
the greater interaction with the arene ring orbital of appro- termined by PES is 15°. Contour plots of the orbitals for
priate symmetry (39). This analysis compares well with that of 1-3 that correspond to the ionizations evaluated by photoelec-
( 5-tBuC5H4)2Zr(Se2C6H4) (39), for which the first band was tron spectroscopy are shown in Fig. 5. The HOMO in 1 is
assigned as a combination of Se and Se ionizations. primarily a metal in-plane orbital, whereas it is primarily a
Compound 2 shows three low-energy ionizations, one at sulfur out-of-plane orbital in 2 and 3. The HOMO-1 orbital
6.29 eV and an overlapping pair of peaks at 7.04 eV and 7.24 for 2 is a metal in-plane orbital. As mentioned earlier, the
eV. The HeII data for 2 clearly show an increase in the rela- metal-based ionization has similar energy for 1 and 2. Thus,
tive intensity of the middle band, and perhaps a slight de- dithiolate appears to buffer the electron density at the metal
crease in the relative intensity of the highest energy band. center by affecting the overlap of S orbitals with the metal
These results imply that the middle band (7.04 eV) is mainly center, thereby overcoming the striking differences of do-
metal-based, the lowest energy band (6.29 eV) is primarily S nor atoms (N and O) in 1 and donor Cp ligands in 2. Fold-
with some additional Mo 4d or C 2p character, and the high- ing of the ene-dithiolate can influence this overlap of S (out-
est energy band (7.24 eV) is S . The ratio of the areas of the of-plane) and metal in-plane orbitals. The HOMO-2 orbital
3722 www.pnas.org cgi doi 10.1073 pnas.0636832100 Joshi et al.

5. SPECIAL FEATURE
the ionizations from primarily metal-based orbitals and pri-
marily S -based orbitals can be experimentally distinguished
from one another. In addition, we have unambiguously dem-
onstrated that the symmetric S orbital, which can interact
with the in-plane metal orbital on bending, is more easily ion-
ized than the antisymmetric S orbital. These results experi-
mentally verify the bonding model originally put forth by
Lauher and Hoffmann (27) for bent-metallocene dithiolate
compounds such as 2 and 3. Our analysis and assignment of
the low-energy ionizations of compounds 2 and 3 also provide
a framework for investigation and direct assignment of the S
and metal-based ionizations in related metal dithiolate sys-
tems that may be more strongly mixed than 2 and 3 or that
may have less favorable separation of their metal-sulfur re-
gion from the ionizations of other ligands.
The variation in the fold angle of the dithiolate ligand re-
flects the electron occupation in the equatorial in-plane metal
Fig. 4. Graph of orbital eigenvalues against fold angle for 2. The geometry orbital, as has been noted (11, 27). Folding of the dithiolate
optimized coordinates of the Cp2MoS2 core of 2 were kept fixed, and the ligand enables the S electron density to modulate the elec-
benzene group was rotated relative to the MS2 plane while keeping the bond tron density in the equatorial plane of the metal, and thus
lengths constant. folding can play a very significant role in the metal–sulfur
anisotropic bonding interaction. In the case of 3, which has
for 1 and 2 and the HOMO-1 orbital for 3 are primarily the formally a Ti(IV) d0 metal center, the dithiolate ligand can be
thought of as a six-electron donor. Each of the thiolate -
CHEMISTRY
antisymmetric sulfur (S ) orbitals with little contribution
from the metal. The symmetric S orbital has the right sym- orbitals provides two electrons, and two additional electrons
metry and energy to match the metal in-plane orbital on fold- come from the S orbital. Hence, folding the dithiolate ligand
ing of the dithiolate unit, and the substantial mixing of the effectively stabilizes 3 as an 18-electron complex. This ‘‘di-
out-of-plane S orbitals and metal in-plane orbital on folding thiolate folding effect’’ is in contrast to the nitrosyl group
is shown experimentally by the intensity changes observed in where the transformation from linear to bent coordination of
the HeI and HeII spectra of 2 and 3 (Fig. 3). the ligand transfers a pair of electrons from the metal to a
localized orbital on the ligand (54).
Conclusions
The gas-phase photoelectron spectra of Cp2M(bdt), M Ti Implications for Enzymes. For molybdenum and tungsten en-
(3) and Mo (2) clearly show that, under favorable conditions, zymes the ‘‘dithiolate-folding-effect’’ of the S2pdt ligand may
Fig. 5. Calculated frontier orbitals (HOMO, HOMO-1, and HOMO-2) of 1–3. All contours have the same cutoff level (0.05).
Joshi et al. PNAS April 1, 2003 vol. 100 no. 7 3723

6. be important in stabilizing the multiple oxidation states that ing with an empty metal orbital, as shown here for the d0 Ti
result from electron transfer or oxygen atom transfer (OAT). complex (3), or by localization of electron density on the S
For example, in sulfite oxidase (Fig. 1), reduction of the orbitals in the presence of a filled metal orbital, as shown
metal in-plane orbital due to the release of an equatorial oxy- here for the d2 Mo complex (2). Dithiolate folding may also
gen atom during OAT should make the dithiolene unit of provide a mechanism for the sulfur- orbitals of the S2pdt
S2pdt more planar compared with the fully oxidized enzyme. ligand to act as an effective electron transfer pathway from
In this regard, we note that the calculated dithiolate fold an- the in-plane orbitals on the metal center to other redox part-
gles for the two chemically equivalent, but crystallographically ners via the pyranopterin. Finally, we note that for molybde-
distinct, molybdenum centers in sulfite oxidase of 6.6° and num and tungsten enzymes the energies involved in substrate
7.0° (Table 1) are smaller than that for the oxidized center of binding, docking with electron transfer partners, and dynamic
aldehyde oxidoreductase (16.6°), whose oxidized structure has motions of the protein skeleton, may modulate the dithiolate
been determined to high resolution (1.28 Å) (15). The exact fold angle and, consequently, the electron distribution, overall
oxidation state of sulfite oxidase in the crystal structure is not reduction potential and reactivity of the metal center.
known, but there is evidence for photoreduction of the mo-
lybdenum center in the synchrotron beam during data collec- Supporting Information
tion (5, 55). The fold angle studies on model systems support Geometry optimized and crystal structure coordinates for
the view that the reported structure of sulfite oxidase (5) is of 1–3, selected computational input, and results are available in
a reduced form of the enzyme. Dithiolate folding can also Tables 3–11, which are published as supporting information
modify the electropositive nature of the metal center by vary- on the PNAS web site.
ing the overlap of sulfur lone pairs with the metal in-plane
orbital. The S orbitals of dithiolate can therefore serve as an Support by National Institutes of Health Grant GM-37773 (to J.H.E.)
essential instrument for the buffering of electron density at and National Science Foundation Grant CHE-9618900 (to D.L.L.) is
the metal center by either involving themselves in strong mix- gratefully acknowledged.
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