Molecular recognition and reactivity of ruthenium(II) bipyridine barbituric acid guests in the presence of complementary hosts: Ruthenium(II) promoted enolization of barbituric acids in guest-host complexes

Article abstract of DOI:10.1021/ja971481y

The binding of the host H1 (N,N'-bis(6-pivalamidopyrid-2-yl)-3,5- pyridinedicarboxamide) to three different ruthenium polypyridine complexes with an attached barbituric acid and barbital moieties (RuG1, RuG2, RuG3) (where G1 = 5-[4-(4'-methyl)-2,2'-bipyridylidene]-2,4,6-(1H,3H,5H)- pyrimidinetrione, G2 = 5-[4-(4'-methyl)-2,2'-bipyridyl]methyl-2,4,6- (1H,3H,5H)-pyrimidinetrione, and G3 = 5-ethyl, 5-[4-(4'-methyl)-2,2'- bipyridyl]methyl-2,4,6-(1H,3H,5H)-pyrimidinetrione) and Ru = (4,4'-di-tert- butyl-bpy)₂Ru (bpy = 2,2'-bipyridine) has been studied in chlorinated solvents by NMR and fluorescence titrations. Significant binding was only observed between H1 and the RuG2 series, while steric hindrance significantly diminished binding between H1 and RuG1 or RUG3. The high binding constant for RuG2 was related to the presence of the enolate form of the barbituric acid guest which forms strong H-bonds with the complementary host H1. For the organic barbituric acid and barbital guests, the keto and enol bind only weakly to H1 (K ~ 10² M^-1); binding is further increased in the presence of base to generate the enolate. In contrast, formation of the RuG2 enolate occurs upon binding to H1 without any additional base. The ruthenium polypyridine cation (compared to the organic barbituric acid derivatives) facilitates ionization of the enol to enolate thus producing a better complementary H-bonding site between the guest and host. Molecular mechanics calculations confirmed the experimental observations that the enolate has the highest binding constant to the Host H1, while the corresponding enol form has the weakest binding.

Full text of DOI:10.1021/ja971481y

J. Am. Chem. Soc. 1997, 119, 12849-12858
12849
Molecular Recognition and Reactivity of Ruthenium(II)
Bipyridine Barbituric Acid Guests in the Presence of
Complementary Hosts: Ruthenium(II) Promoted Enolization of
Barbituric Acids in Guest-Host Complexes
Teen Chin, Zhinong Gao, Isabelle Lelouche, Yeung-gyo K. Shin, Ashok Purandare,
Spencer Knapp,* and Stephan S. Isied*,†
Contribution from the Department of Chemistry, Rutgers, The State UniVersity of New Jersey,
Piscataway, New Jersey 08855
ReceiVed May 7, 1997X
Abstract: The binding of the host H1 (N,N′-bis(6-pivalamidopyrid-2-yl)-3,5-pyridinedicarboxamide) to three different
ruthenium polypyridine complexes with an attached barbituric acid and barbital moieties (RuG1, RuG2, RuG3)
(where G1 ) 5-[4-(4′-methyl)-2,2′-bipyridylidene]-2,4,6-(1H,3H,5H)-pyrimidinetrione, G2 ) 5-[4-(4′-methyl)-2,2′-
bipyridyl]methyl-2,4,6-(1H,3H,5H)-pyrimidinetrione, and G3 ) 5-ethyl, 5-[4-(4′-methyl)-2,2′-bipyridyl]methyl-2,4,6-
(1H,3H,5H)-pyrimidinetrione) and Ru ) (4,4′-di-tert-butyl-bpy)2Ru (bpy ) 2,2′-bipyridine) has been studied in
chlorinated solvents by NMR and fluorescence titrations. Significant binding was only observed between H1 and
the RuG2 series, while steric hindrance significantly diminished binding between H1 and RuG1 or RuG3. The
high binding constant for RuG2 was related to the presence of the enolate form of the barbituric acid guest which
forms strong H-bonds with the complementary host H1. For the organic barbituric acid and barbital guests, the keto
and enol bind only weakly to H1 (K ∼ 102 M-1); binding is further increased in the presence of base to generate the
enolate. In contrast, formation of the RuG2 enolate occurs upon binding to H1 without any additional base. The
ruthenium polypyridine cation (compared to the organic barbituric acid derivatives) facilitates ionization of the enol
to enolate thus producing a better complementary H-bonding site between the guest and host. Molecular mechanics
calculations confirmed the experimental observatons that the enolate has the highest binding constant to the Host
H1, while the corresponding enol form has the weakest binding.
The design of synthetic guest and host molecules which
undergo molecular recognition using weak noncovalent interac-
tions is an emerging field1 with many potential applications.2-6
Multiple noncovalent interactions between guest and host
molecules can result in strong binding even in highly polar
solvents. These weak interactions can be major contributors
to the binding of drugs to proteins and DNA targets and can
form the basis for developing sensors to monitor the concentra-
tion of specific ions or molecules.2-6
Molecules with H-bonding recognition sites as their primary
charge-transfer pathway are important for understanding the role
of the electronic structure of peptides in controlling charge
transport processes, especially those occurring in weakly polar
protein interfacial environments.7 Several model systems
describing charge transfer processes that occur across H-bonding
interfaces have been reported.8-18
We have demonstrated the presence of efficient long-range
electron-transfer pathways in conformationally rigid peptides
that are covalently linked to metal ion donors and acceptors.19,20
In extending these studies to noncovalently linked donors and
acceptors, we selected ruthenium(II) polypyridine barbituric
(8) Chang, S. K.; Hamilton, A. D. J. Am. Chem. Soc. 1988, 110, 1318.
(9) (a) Tecilla, P.; Dixon, R. P.; Slobodkin, G.; Alavi, D. S.; Waldeck,
D. H.; Hamilton, A. D. J. Am. Chem. Soc. 1990, 112, 9408. (b) Chang, S.
K.; Engen, D. V.; Fan, E.; Hamilton, A. D. J. Am. Chem. Soc. 1991, 113,
7640. (c) Hamilton, A. D. Advances in Supramolecular Chemistry, Gokel,
G. W., Ed.; 1990, 1, 1. JAI Press LTD. London, England.
(10) (a) Roberts, J. A.; Kirby, J. P.; Nocera, D. G.; J. Am. Chem. Soc.
1995, 117, 8051. (b) Turro, C.; Chang, C. K.; Leroi, G. E.; Cukier, R. I.;
Nocera, D. G. J. Am. Chem. Soc. 1992, 114, 6233.
(11) (a) Bernan, A.; Izraeli, E. S.; Lavanon, H.; Wang, B.; Sessler, J. L.
J. Am. Chem. Soc. 1995, 117, 8252. (b) Sessler, J. L.; Bing, W.; Harriman,
A. J. Am. Chem. Soc. 1993, 115, 10418. (c) Harrriman, A.; Magda, D.;
Sessler, J. L. J. Am. Chem. Soc., Chem. Commun. 1991, 345. (d) Harriman,
A.; Magda, D. J.; Sessler, J. L. J. Phys. Chem. 1991, 95, 1530. (e) Harriman,
A.; Kubo, Y.; Sessler, J. L. J. Am. Chem. Soc. 1992, 114, 388.
(12) de Rege, P. J. F.; Williams, S. A.; Therien, M. J. Science 1995,
269, 1409.
† E-mail address: Isied@rutchem.rutgers.edu.
X Abstract published in AdVance ACS Abstracts, December 15, 1997.
(1) For a recent general review in this area, see: Lawrence, D. S., Jiang,
T., Levett, M. Chem ReV. 1995, 95, 2229.
(2) Feibuch, B.; Figueroa, A.; Charles, R.; Onan, K. D.; Feibush, P.;
Karger, B. L. J. Am. Chem. Soc. 1986, 108, 3310.
(3) Carmack, G. D.; Freiser, H. Anal. Chem. 1977, 49, 1577.
(4) Steinbeck, M.; Ringsdorf, H. J. Chem. Soc., Chem. Commun. 1996,
1193.
(5) Bethell, D.; Dougherty, G.; Cupertino, D. C. J. Chem. Soc., Chem.
Commun. 1995, 675.
(13) Yang, J.; Seneviratne, D.; Arbatin, G.; Andersson, A. M.; Curtis, J.
C. J. Am. Chem. Soc. 1997, in press.
(14) Aoyama, Y.; Asakawa, M.; Matsui, Y.; Ogoshi, H. J. Am. Chem.
Soc. 1991, 113, 6233.
(15) Miyasaka, H.; Tabata, A.; Kamada, K.; Mataga, N.; J. Am. Chem.
Soc. 1993, 115, 7335.
(16) (a) Zerkowski, J. A.; Seto, C. T.; Whitesides, G. M. J. Am. Chem.
Soc. 1992, 114, 5473. (b) Seto, C. T.; Whitesides, G. M. J. Am. Chem.
Soc. 1991, 113, 712.
(6) (a) Szemes, F.; Hesek, D.; Chen, A.; Dent, S. W.; Drew, M. G. B.;
Goulden, A. J.; Graydon, A. R.; Grieve, A.; Mortimer, R. J.; Wear, T.;
Weightman, J. S.; Beer, P. D. Inorg. Chem. 1996, 35, 5868. (b) Beer, P.
D.; Chen, S.; Goulden, A. J.; Grieve, A.; Hesek, D.; Szemes, F.; Wear, T.
J. J. Chem. Soc. Chem. Commun. 1994, 1269. (c) Beer, P. D.; Drew, M. G.
B.; Hazlewood, C.; Hesek, D.; Hodacova, J.; Stokes, S. E. J. Chem. Soc.,
Chem. Commun. 1993, 229. (d) Beer, P. D.; Szemes, F. J. Chem. Soc.,
Chem. Commun. 1995, 2245. (e) Beer, P. D.; Dent, S. W.; Wear, T. J. J.
Chem. Soc., Dalton Trans. 1996, 3241.
(17) (a) Lehn, J. M.; Mascal, M.; DeClan, A.; Fischer, J. J. Chem. Soc.,
Perkin Trans. 2 1992 461. (b) Lehn, J. M.; DeClan, A.; Fischer, J. J. Chem.
Soc., Chem Commun. 1990, 479.
(7) For an interfacial electron transfer protein-protein structure, see:
Pelletier, H.; Kraut, J. Science 1992, 258, 1748.
(18) Motesharei, K.; Myles, D. C. J Am. Chem. Soc. 1994, 116, 7413.
S0002-7863(97)01481-9 CCC: $14.00 © 1997 American Chemical Society

12850 J. Am. Chem. Soc., Vol. 119, No. 52, 1997
Chin et al.
Figure 2. Keto, enol, and enolate forms of barbituric acid derivatives
which are possible when C-5 has one or more protons attached to it.
Figure 1. Molecular structure of the Host, H1, and three different
ruthenium polypyridine guests. For RuG1 and RuG3, R ) 4,4′-di-
tert-butyl-bpy (bpy ) 2,2′-bipyridine), and for RuG2, R ) 4,4′-di-
tert-butyl-bpy, 4,4′-dimethyl-bpy, and bpy.
4,4′-di-tert-butyl-bpy (bpy ) 2,2′-bipyridine), and for RuG2,
R ) 4,4′-di-tert-butyl-bpy, 4,4′-dimethyl-bpy, and bpy.
The synthesis of H1 is shown in Scheme 3. The pivaloyl
group was used in order to increase the solubility and reduce
aggregation22 of the host molecules in low polarity solvents
(such as CH2Cl2 and CHCl3) where the binding of H1 to
barbituric acid derivatives was studied. The organic barbituric
acid derivatives were characterized by NMR, HPLC, and mass
spectrometric techniques, as described in the Experimental
Section. In addition, UV-visible absorption, emission spectra,
and oxidation/reduction potentials were measured for the
ruthenium guest molecules. The complexes are all soluble in
CH2Cl2 as their hexafluorophosphate salts, with RuG2 being
the most soluble. The absorption and emission spectra of the
ruthenium polypyridyl barbituric acid derivatives (Table 1) bear
close similarities to those of the parent compound [Ru-
acid derivatives as guest molecules with H-bonding molecular
recognition properties for specific complementary host
molecules.9a Alkylated barbituric acid guests and 2,4,6-triami-
nopyrimidines and 2,6-diaminopyridine amide hosts have been
used to probe molecular recognition by H-bonding interactions
in several studies.8,9
This paper reports on the interaction between ruthenium(II)
polypyridine barbituric acid derivatives with a complementary
host (N,N′-bis(6-pivalamidopyrid-2-yl)-3,5-pyridinedicarbox-
amide) H1 (Figure 1). Unexpectedly high binding is observed
when a ruthenium(II) polypyridine barbituric acid cation (with
appropriate molecular architecture) binds to H1, compared to
the binding of the analogous barbituric acid derivatives without
the ruthenium(II) polypyridine. These high binding-constants
are discussed in terms of the keto-enol equilibria of the
barbituric acid induced by the substitution of ruthenium(II)
polypyridine at the C-5 carbon of the barbituric acid.
(bpy)3]2+ 23
The oxidation and reduction potentials for the
.
ruthenium complexes (in CH3CN) are shown in Table 2.
Binding of Ruthenium Barbituric Acid Derivatives to H1
Host. The binding to H1 of three closely related ruthenium
bipyridine barbituric acid complexes (Figure 1), which differ
in the mode of attachment of the barbital ring to the ruthenium
bipyridine, was studied by NMR and fluorescence techniques.
Only RuG2, the saturated analogue, can undergo keto-enol
equilibria (enolization of the RuG1 and RuG3 barbituric acid
complexes at C-5 is not possible). The binding of these
ruthenium complexes to H1 was carried out by following the
change in the NMR chemical shift of amide protons of H1 (and
in some cases, the amide groups of the barbituric acid ring).
Alternatively, changes in the fluorescence intensity of RuG1,
RuG2, and RuG3 were followed as H1 was added.24 Titration
of H1 with RuG1 or RuG3 did not show any measurable
changes in the NMR of the amide protons of H1 (in CDCl3) or
any measurable changes in the fluorescence signal intensity (in
CH2Cl2). These results are consistent with immeasurably small
binding between H1 and RuG1 and RuG3, respectively.
Results and Discussion
Synthesis and Characterization of Guest and Host Mol-
ecules. The guest molecules in our studies were either
dialkylated, unsaturated, or saturated at the barbituric acid C-5
position (Figure 1), but only the saturated derivatives can
undergo keto-enol equilibria (Figure 2). Comparative binding
of the barbituric acids, and their analogous ruthenium deriva-
tives, to H1 can be best discussed in terms of this keto-enol
equilibria.
The barbituric acid derivatives shown in Figure 1 were
synthesized from the corresponding aldehydes and barbituric
acid (Scheme 1), except for G3, which was synthesized using
a modified literature procedure21 (Scheme 2). The G2, RuG2,
and B-C3H6 were all obtained by reduction of their respective
unsaturated precursors. The synthesis of the guests G1, G2
and their respective ruthenium(II) complexes RuG1, RuG2 is
shown in Scheme 1. G3 and corresponding ruthenium complex,
RuG3, are shown in Scheme 2. For RuG1 and RuG3, R )
When RuG2 was titrated with H1 (in CDCl3), large changes
occur in the amide protons of H1 and those of the barbituric
acid ring of RuG2 as shown in the NMR spectra in Figure 3.
(19) Isied, S. S.; Moreira, I.; Ogawa, M. Y.; Vassilian, A.; Arbo, B.;
Sun, J. J. Photochem. Photobiol. A: Chem. 1994, 82, 203.
(20) Ogawa, M. Y.; Moreira, I.; Wishart, J. F.; Isied, S. S. Chem. Phys.
1993, 176, 589.
(21) Ciana, L. D.; Hamachi, I.; Meyer, T. J. J. Org. Chem. 1989, 54,
1731.
(22) Tamiaki, H.; Nomura, K.; Maruyama, K. Bull. Chem. Soc. Jpn. 1994,
67, 1863.
(23) Juris, A.; Balzani, V.; Barigelletti, F.; Campagna, S.; Belser, P.;
von Zelewsky, A. Coord. Chem. ReV. 1988, 84, 85.
(24) Schneider, H. J.; Kraemer, R.; Simova, S.; Schneider, U. J. Am.
Chem. Soc. 1988, 110, 6442.

Ruthenium(II) Bipyridine Barbituric Acid Guests
J. Am. Chem. Soc., Vol. 119, No. 52, 1997 12851
Scheme 1. Synthesis of the Guests G1 and G2 and the Corresponding RuG1 and RuG2 Complexes
Scheme 2. Synthesis of the Guest G3
fluorescence changes that resulted when controlled amounts of
H1 were added to dilute solutions of RuG2 (e5 µmol) (Figure
4).
To show that the binding is only sensitive to the barbituric
acid substituted bipyridine derivative, three different complexes
with substituents on the bipyridines not attached to the barbituric
acid were synthesized and studied. These are (4,4′-di-tert-butyl-
bpy)2RuG2, (4,4′-dimethyl-bpy)2RuG2, and (bpy)2RuG2. The
solubility of these complexes in CH2Cl2 as PF6 salts decreased
as the size of the alkyl substituent decreased; however, the
similar binding constants observed for these three G2 derivatives
with H1 (Table 3) is strong evidence that they bind to H1 in an
almost identical manner.
The difference in binding of the respective ruthenium
complexes to H1 is related to the molecular architecture of the
ruthenium barbituric acid complexes and to the cavity of the
H1 host. In RuG1, the olefinic carbon extends the planarity
of the bipyridine ring, making the barbituric acid a poor fit for
the cavity of H1. This poor fit, as shown by molecular modeling
(vide supra), can explain the immeasurably low binding constant
between RuG1 and H1. For RuG3, higher binding to H1 is
predicted by molecular modeling methods; however, the binding
is still not measurable experimentally. In RuG3 (where a-
These changes are indicative of high binding constants. The
NMR titration is used to obtain information on the stoichiometry
(1:1) and binding of H1 to RuG2 and also to provide evidence
on the molecular nature of the interaction between H1 and
RuG2 (Figure 3). Additionally a Jobs plot of fluorescence
changes also showed the 1:1 stoichiometry.24 The binding
constants for these 1:1 complexes were determined from the

12852 J. Am. Chem. Soc., Vol. 119, No. 52, 1997
Chin et al.
Scheme 3. Synthesis of the Host H1 (R ) Methyl and tert-Butyl)
Table 1. Spectroscopic Data for the Ru(II) Polypyridyl
Compounds in CH2Cl2 at 290 K
In agreement with this model, replacement of the pivaloyl
groups on H1 with less sterically demanding alkanoyl groups
should result in even higher binding constants for RuG2 to these
new hosts.
compounds
λ
MLCT (nm)
λ
em(nm)
[(DTB-bpy)2Ru(G1)]2+
[(DTB-bpy)2Ru(G2)]2+
[(DTB-bpy)2Ru(G3)]2+
[(DTB-bpy)3Ru]2+
462
462
462
460
460
462
454
610
610
610
607
610
610
594
Binding of Organic Barbituric Acid Derivatives to H1.
In comparison to the high binding constant of RuG2 to H1,
the binding of barbituric acids to H1 was only modest under
the same conditions (in CHCl3 and CH2Cl2). Their binding
constants were determined from the change in the position of
the amide N-H resonances of H1 upon binding to the different
barbituric acids.26 Four derivatives soluble in CHCl3 and CH2-
Cl2 (Figure 6) were examined for the effect of keto-enol
equilibria on their binding constants to H1. For the BC3H6,
BCF3, both keto- and enol-forms are accessible (as seen by
changes of the NMR chemical shift of the amide protons of
H1 in Figure 7),27-30 while for the alkylated (Barbital) and
unsaturated BC3H3 barbituric acids, only keto forms are
accessible.
[(bpy)2Ru(G2)]2+
[(4,4′-(CH3)2bpy)2Ru(G2)]2+
[(bpy)3Ru]2+
Table 2. Oxidation and Reduction Potentialsa for the Ru(II)
Polypyridyl Compounds
oxidationc
reductionsc
Eo (+2/+3) Eo(+2/+) Eo(+/φ) Eo(φ/-)
compoundsb
(V)
(V)
(V)
(V)
[(DTB-bpy)2Ru(G1)]2+
[(DTB-bpy)2Ru(G2)]2+
[(DTB-bpy)2Ru(G3)]2+
[(DTB-bpy)3Ru]2+
[(bpy)3Ru]2+
+1.18
+1.18
+1.14
+1.11
+1.28
-1.48
-1.49
-1.48
-1.69
-1.74
-1.67
-2.05
1.97
-1.96
The amount of the keto- and enol-forms of the barbituric acids
in different solvents can be determined from the assignment of
the multiplet C-H resonance for the carbon connecting the
barbital to the organic group. From this assignment, the BC3H6
exists only in the keto-form in CHCl3 and in acetone, while
BCF3 exists in both the keto- and enol-forms (6.5:1) in CHCl3
and only in the enol-form (Figure 7b) in the more polar solvent
acetone. Barbital and BC3H3 exist only in the keto form. The
binding to H1 of Barbital, BC3H3, and BC3H6 are all very
similar (Table 3), since they have similar structures and all exist
in the keto-form in CDCl3. For BCF3, where the presence of
the electron withdrawing group (CF3) (compared to BC3H6)
enhances the enol formation (6.5:1 enol/keto in CDCl3), a lower
binding constant to H1 is observe. This is consistent with the
enol form disrupting the symmetry of the H-bonding network
to H1.
-1.35
-1.55
a Scan rate ) 0.2 V/s. b As their PF6 salts. c Potentials are measured
vs SSCE in 0.1 M n-Bu4NPF6 in acetonitrile.
CH2 group connects the bipyridine ring and the barbituric acid
C-5 position), the dihedral angle between the barbituric acid
ring and the bipyridine ring is nearly perpendicular and thus
not planar (compared to RuG1). This lack of planarity is
expected to improve the steric effect of the bipyridine ring on
the H1 cavity, resulting in a better fit and higher binding;
however, the bulky pivaloyl groups on H1 reduce the binding
of RuG3 to H1, and thus no measurable binding is observed
for this guest/host pair. Replacing the pivaloyl group with a
less sterically demanding butanoyl group makes this host more
accomodating for the bulky ruthenium polypyridine moiety. The
binding of RuG3 to a host with the n-butanoyl (instead of the
pivaloyl) group becomes measurable from chemical shifts of
the amide bonds in an NMR titration (K ∼ 80 M-1).25
In order to generate the enolate form of one of the barbituric
acids, BCF3 was studied, since it already exists predominantly
in the enol form in CDCl3 (in contrast to BC3H6). An NMR
titration of a 1:1 complex of H1 and BCF3 with 1 equiv of the
base (1,8-bis(N,N-dimethylamine)naphthalene (Proton Sponge))
is shown in Figure 8. Large changes in the amide chemical
shift observed upon addition of this base are an indication of a
strong binding. Four different types of protons show additional
shifts upon titration of BCF3:H1 with base. These are the four
amide protons on H1 (a,b), the two NH of the barbituric group
(c) and the CH2 protons of the carbon that connects the barbituric
The binding of RuG2 and RuG3 to H1 is expected to be
similar, since the absence of the ethyl group on the barbituric
acid ring in RuG2 is not expected to be significant. Instead,
the keto-enol capability of RuG2 (Figure 2) provides a major
difference between RuG2 and RuG3, which accounts for the
additional four to five orders of magnitude increase in binding
constant of RuG2 to H1 over RuG3. The enolate form of
RuG2 (with a negative charge delocalized over the two oxygen
atoms of the barbituric ring) provides a strong hydrogen bonding
network with six contacts between the outer amide protons of
H1 and the negatively charged oxygen atoms of the barbituric
acid ring (Figure 5). The enol form of RuG2 cannot have high
binding to H1, because the conjugation at the C-5 of the
barbituric acid is broken and the hydrogen bonding symmetry
required to match the host is disrupted.
(26) (a) Wilcox, C. S.; Cowart, M. D. Tetrahedron Lett. 1986, 27, 5563.
(b) Wilcox, C. S. Frontiers in Supramolecular Organic Chemistry &
Photochemistry; Scheider, H. J.; Durr, H., Eds.; VCH: Weinheim, Germany,
1990.
(27) Ascenso, J.; Candida, M.; Vaz, T. A.; Frausto da Silva, J. J. R.
Inorg. Nucl. Chem. 1981, 43, 1255.
(28) Neville, G. A.; Avdovich, H. W.; By, A. W. Can. J. Chem. 1970,
48, 2274.
(29) Glasel, J. A. Org. Magn. Reson. 1969, 1, 481.
(30) Kelly-Rowley, A. M.; Lynch, V. M.; Anslyn, E. V. J. Am. Chem.
Soc. 1995, 117, 3438.
(25) Ghaddar, T.; Isied, S. Manuscript in preparation for publication.

Ruthenium(II) Bipyridine Barbituric Acid Guests
J. Am. Chem. Soc., Vol. 119, No. 52, 1997 12853
Figure 3. NMR Titration of H1 (in CHCl3) with varying amounts of RuG2. The guest and host are labeled and their assignment is labeled on the
molecule and on the spectra as the binding between the guest and the host proceeds.
Figure 5. The molecular structure of the RuG2:H1 complex (with
the guest in the enolate form): formula (A) and the three-dimensional
energy-minimized structure (B).
Figure 4. The fluorescence spectrum of RuG2 (6.8 × 10-6 M in CH2-
Cl2) and the increase in intensity observed when excess H1 (5.4 ×
10-5 M) are added (λexc) 435 nm).
Table 3. Binding of Barbituric Acid Derivatives to Receptor H1
compounds
Ka (M-1
)
[(DTB-bpy)2Ru(G1)]2+
[(DTB-bpy)2Ru(G2)]2+
[(DTB-bpy)2Ru(G3)]2+
(4,4′-(CH3)2bpy)2Ru(G2)]2+
[(bpy)2Ru(G2)]2+
Barbital
BC3H6
BC3H3
BCF3
<10 a
3.0 × 105 a
<10 a
2.8 × 105 a
3.1 × 105 a
4.5 ( 1 × 102 b
4.7 ( 1 × 102 b
5.3 ( 1 × 102 b
0.7 ( 0.3 × 102 b
Figure 6. Barbital derivatives: alkylated, unsaturated, and reduced
types.
acid is in the enolate form (which is a conjugated structure with
a negative charge delocalized over three carbon and two oxygen
atoms). Intermediate to weak binding is observed with barbi-
turic acids that only exist in the keto form. The smallest binding
occurs for the enol form because it disrupts the complimentary
H-bonding of the guest to the host. In comparison to the RuG2
complexes where strong binding to H1 occurs, the barbituric
acids without ruthenium studied show that both the presence
of electron withdrawing groups on the barbituric acids
a Obtained from fluorescence titration in CH2Cl2. b Obtained from
1NMR titration data in CDCl3.
acid ring to the organic substituent (d) (see also Figure 8). The
strong binding is attributed to the formation of the enolate form
of the BCF3 and an approximate binding constant, K ∼ 104
M-1 can be calculated from the titration data.
The binding of the different forms of barbituric acids to the
host H1 is illustrated in Scheme 4. The strongest binding of
barbituric acid derivatives to H1 is observed when the barbituric

12854 J. Am. Chem. Soc., Vol. 119, No. 52, 1997
Chin et al.
the 2,6-diaminopyridine rings are added.25 Such molecular
assemblies should result in increased binding constants and make
detailed studies of electron transfer and energy transfer across
H-bonding networks possible.
Using 2,6-dicarboxypyridine as part of the molecular design
of H1 is also useful for the attachment of kinetically inert metal
ions such as RuIII, CoIII, or OsIII, to the central pyridyl nitrogen
in order to study intramolecular energy transfer and electron
transfer across these hydrogen bonding networks.
Estimation of Binding Constants from Molecular Model-
ing Calculations. The binding of the guests to H1, K′eq, was
calculated by considering the enthalpy, ∆H°, instead of the free
energy, ∆G°, for the association of H1 with guests (and thus
the prime notation in K′eq). Although the ∆S° upon binding
may not be negligible, the ∆S° of these reactions is expected
to remain roughly the same for the series of reactions studied.
Solvent effects for the different guests were also assumed to be
constant throughout the series. With these approximations, the
binding constants were calculated and used to predict the relative
binding for different guest-host combinations.
The enthalpy change for the formation of the guest-host
complex, guest + H1 (host) f [guest-H1], is defined as ∆H°
) H°[guest-H1] - H°(guest) - H°(H1). The binding constants
calculated from K′eq) e-∆H°/RT at 25 °C (RT ) 0.592 kcal) and
the H°[guest-H1], H°(guest), and H°(H1) obtained from the
energetics of the optimized structures for the guest-host
molecules are described below.
The host molecule H1 was assumed to have a planar structure
(except for the pivaloyl group). The host H1 structure can be
optimized to either the cis or trans-conformation with respect
to the CdO bonds closest to the central pyridine ring. Only
the cis-conformation can form the experimentally derived 1:1
guest/host complex, while the trans-conformation can lead to a
polymeric structure. The cis-conformation (minimized energy
-112.0 kcal/mol) was used even though the trans-conformation
has lower energy (minimized energy -118.1 kcal/mol) and is
therefore more stable than the cis-conformation by ∼6 kcal/
mol.
In the unsaturated G1 and in RuG1, the dihedral angle of
the barbiturate ring and the bipyridine moiety was found to be
∼60°, indicating steric interaction between the carbonyl group
and the hydrogen at the 3-position of the bipyridine rings. A
grossly distorted ring structure results when RuG1 is introduced
into the cavity of H1, because the pivaloyl group cannot fit
well into the groove between the two bipyridine ligands of the
RuII(bpy)2. Thus, an extremely small binding constant is
calculated for RuG1 (Table 4). Experimentally the binding
constant was not measurable (K < 10 M-1).
For the G2 and RuG2, the reduced olefinic minimized bridge
structure takes a cis arrangement with respect to the barbiturate
ring so that the bipyridine group is almost stacked on top of
the barbiturate ring. Upon formation of the G2 enol or enolate,
the planes of the bipyridine and the barbiturate rings become
perpendicular to each other and therefore relieve the steric
constraints imposed on the RuG1 conformation (i.e., interacting
with the pivaloyl groups) (Figure 11). The enolate form of G2
possesses a mirror plane with a bipyridine group that bisects
the barbiturate ring when the orientation of peripheral bipyridine
groups on the ruthenium are ignored. Therefore, the RuG2
complex fits well into the H1 cavity, resulting in high binding.
In the enol form, the hydroxyl group breaks the symmetry,
disrupts the H-bonding between the guest and the host and
results in lower binding (Table 4). The G3 only exists in the
keto form, because of the replacement of hydrogen by the ethyl
group at the carbon of the barbituric acid ring in G3.
Figure 7. NMR of the C-5 protons in BC3H6, BCF3, and RuG2 in
different deuterated solvents.
and the addition of a strong base are required to affect a similarly
strong binding to H1.
Binding of Alkylated Barbitals to Related Receptors. The
binding of barbital and alkylated barbitals to a number of linear
and macrocyclic receptors was studied by Hamilton and co-
workers.9a In their studies, hosts similar to H1 were used with
n-butanamide instead of pivalamide side chains (Figure 1).
Higher binding constants were reported (ranging from 104-
106 M-1) for hosts with favorably maximized electronic effects
and alkylated barbitals with no ability to form keto-enol
equilibria.9a
Comparison of the binding data reported for H1 with those
reported earlier lead to the conclusion that the bulky pivaloyl
groups (used in H1 to prevent aggregation) as well as the
ruthenium polypyridine moiety present additional steric effects
for the H-bonding cavity of H1 and decrease the binding of
H1 to RuG3 as shown in Figure 9. Whereas the more open
structure of the porphyrin barbital with the phenyl spacer can
accomodate H1 without these additional steric effects, significant
differences were found when the open porphyrin molecules were
compared to the sterically hindered RuG3. The proximity of
the RuII(bpy)2 to the H1 cavity and its octahedral geometry are
therefore responsible for these additional steric effects (compared
to the planar porphyrin that is connected to the barbital derivative
by a phenyl spacer at the C-5 carbon). If a spacer such as a
phenyl group is added to the RuG3, similar binding to the
porphyrin barbital and other alkylated barbitals would be
expected. However, the extent to which such a spacer will
reduce the capability of ruthenium polypyridine barbituic acid
derivatives to undergo keto-enol equilibria is not known at this
time.
The formation of the RuG2 enolate causes C-5 to change
from sp3 to sp2 and as a result moves the barbituric ring away
from the bipyridine ligands (Figure 10) which increases the
binding of RuG2 to H1 because of a modified H-bonding
network. The sp2 carbon formed upon enolization also strength-
ens H-bonding between the negatively charged oxygen atoms
and the amide N-H’s of the H1 host. Future studies will be
directed toward exploiting the keto-enol equilibria affected by
the ruthenium complex as the steric effects induced by the
pivaloyl groups are removed and other changes promoted by

Ruthenium(II) Bipyridine Barbituric Acid Guests
J. Am. Chem. Soc., Vol. 119, No. 52, 1997 12855
Figure 8. NMR titration of a 1:1 complex BCF3:H1 with the base, 1,8-bis-(N,N-dimethylamine)naphthalene (proton sponge). Shift in the amide
protons upon binding is labeled on the molecule and on the spectra. e is the signal for the N,N-dimethyl of the proton sponge.
Scheme 4. A Scheme (Shown for the BCF3 Derivative) for the Binding of Organic Barbituric Acid Derivatives in Their
Different Forms (Keto, Enol, Enolate) to the Host H1 Showing That the Enolate Exhibits the Strongest Binding and the Enol
Exhibits the Weakest Binding
The interaction of H1 with RuG2 using the rigid geometry of
RuG3 is expected to improve its binding relative to RuG2 to
H1 in its keto form (Table 4). The diethyl group of G3 is
assumed to have an all trans-conformation with the axis of the
hydrocarbon chain perpendicular to the barbiturate ring. The
binding constants based on the MM2 calculation (with the
assumptions outlined in the beginning of this section) increase
in the following order: K′eq(enol) < K′eq(keto) < K′eq(enolate)
(Table 4). Experimental observations agree with the trend
predicted by these MM2 calculations.

12856 J. Am. Chem. Soc., Vol. 119, No. 52, 1997
Chin et al.
Figure 11. Three-dimensional structure of the RuG1 complex showing
the steric interaction between the barbituric acid ring and one of the
bipyridine ligands attached to the Ru(II) complex.
can introduce large steric effects that reduce the binding between
H1 and the alkylated and unsaturated barbital derivatives
through their interaction with the substituents at the two ends
of the 2,6-diaminopyridine groups. Overall enhancement in
binding of more than four orders of magnitude can result from
enolate formation at the barbital ring. In this study the role of
the pivaloyl substituents while useful in enhancing the solubility
of the guest/host complex in weakly polar solvents and
preventing aggregation, also turned out to sterically modulate
the H-bonding association between the guest and the host. Other
groups that can increase or decrease binding are currently under
investigation.25
Figure 9. Comparison of the environment around the barbital group
in the open porphyrin guest/host system (A) and in the sterically
hindered ruthenium system (B).
Experimental Section
Solvents and Starting Materials. Chloroform was distilled from
CaCl2, CH2Cl2 and triethylamine from CaH2, and THF from Na/
benzophenone. For electrochemical experiments, commercial CH3CN,
dried over 4Å molecular sieves, was used without further purification.
Commercial deuterated solvents were used as received. The 4,4′-di-
t-Bu-2,2′-bipyridine31 and cis-(4,4′-R-bpy)2RuCl2‚2H2O (where R )
H, CH3, t-Bu, and bpy ) bipyridine) were prepared as described in the
literature.32a The 4′-methyl-2,2′-bipyridine-4-carboxaldehyde33 and
4-bromomethyl-4′-methyl-2,2′-bipyridine dihydrobromide were pre-
pared by literature procedures.21
Figure 10. Three-dimensional structure of RuG2 in the keto and in
the enolate form showing the relief from steric interactions that enolate
formation causes by changing C-5 from sp3 to sp2 carbon.
Instrumentation. HPLC was carried out by using a constant flow
of the buffer (CH3CN/H2O/0.1% NaTFA) and monitoring at 254 nm.
1H and 13C NMR spectra were obtained at 200 MHz. Chemical shifts
are reported in ppm downfield from tetramethylsilane, and coupling
constants are in hertz. Fast atom bombardment mass spectra (FAB-
MS) were taken at the Biomedical Research Core Facilities, University
of Michigan; m/z values are reported for the protonated molecular ions
unless otherwise indicated. Fluorescence spectra were obtained using
a FluoroMax spectrofluorometer Model Spex 20. In voltammetric
studies a three electrode cell configuration with a glassy carbon working
electrode, a Pt auxiliary electrode, and a SCE reference electrode was
used on a BAS 100A electrochemical analyzer. The reference electrode
was placed in a glass tube separated from the bulk solution by a Vycor
frit. After each determination, ferrocene was added to the sample
solution, and its oxidation was measured voltammetrically for calibra-
tion. The supporting electrolyte in all cases was 0.1 M tetrabutylam-
monium hexafluorophosphate. The sample solutions, ∼0.3-0.5 mM,
were purged with argon for 15 min prior to the measurements. The
reported E1/2 values were obtained from the average of the cathodic
and anodic peak potentials at varying scan rates. The redox couples
were considered to have Nernstian behavior based on their peak-to-
Table 4. Calculated Energetics of Host-Guest complexes with H1
(H ) - 112.0 kcal/mol)
energy, kcal/mol
guest
H(guest) H(guest-host)
∆H
e-∆H/RT
G1
G2
G3
Barbital
RuG1
RuG2 (keto)
RuG2 (enol)
RuG2 (enolate)
RuG3
-83.1
-80.6
-77.1
-64.6
-46.0
-42.9
-52.5
-54.4
-46.1
-210.3
-211.7
-209.4
-194.6
-114.7
-160.6
-164.5
-177.3
-165.2
-15.1 1.2 × 1011
-19.1 1.0 × 1014
-20.3 7.6 × 1014
-18.0 1.4 × 1013
43.3 1.8 × 10-32
-5.6 1.4 × 104
0.0 1.0
-10.8 7.8 × 107
-7.0 1.3 × 105
Role of the Ruthenium Complex. The comparison of the
binding constant for RuG2 and BCF3 with H1 shows that the
ruthenium(II) complex favors the enolate formation more than
the unchanged organic substituents. For the organic substituents
with electron withdrawing substitutents (CF3 groups) on the
barbital ring (which enhance enol formation), enolate formation
still requires the addition of a strong base. For the ruthenium
derivatives no base is required to form the enolate. Upon the
formation of the enolate, both the ruthenium barbituric acid and
barbituric acids with organic derivatives strongly bind to H1.
The octahedral structure of the ruthenium complex also plays
a role where the presence of the bipyridine rings close to H1
(31) Sasse, W. H. F. Org. Synth. 1966, 46, 102.
(32) (a) Sullivan, B. P.; Salmon, D. J.; Meyer, T. J. Inorg. Chem. 1978,
17, 333. (b) Belser, V. P.; Zelewsky, V. A. HelV. Chim. Acta 1980, 63,
1675.
(33) (a) Peek, B. M.; Ross, G. T.; Edwards, S. W.; Meyer, G. J.; Meyer,
T. J.; Erickson, B. W. Int. J. Peptide Protein Res. 1991, 38, 114. (b) Strouse,
G. F.; Schoonover, J. R.; Duesing, R.; Boyde, S.; Jones, W. E., Jr.; Meyer,
T. J. Inorg. Chem. 1995, 34, 473.

Ruthenium(II) Bipyridine Barbituric Acid Guests
J. Am. Chem. Soc., Vol. 119, No. 52, 1997 12857
peak separations compared to that of the ferrocene/ferrocenium couple
under the same conditions.
(d, two pyr-H-2,6), 10.43 (s, two CONH); FAB-MS 350 (M + H)+.
Anal. Calcd for C17H15N7O2‚H2O: C, 55.58; H, 4.66; N, 26.69.
Found: C, 55.48; H, 4.51; N, 25.90.
Binding Studies. The binding interaction between the receptor, H1,
and various guest compounds was investigated by 1H NMR and
fluorescence spectroscopy.26 The binding constants were obtained from
a nonlinear least squares curve-fitting of the data to the binding
isotherms. The protocol used for each technique is detailed below.
The fluorescence binding studies were all performed using CH2Cl2
(freshly distilled from CaH2). The glass apparatus was predried in the
oven just prior to use. To exclude moisture, the sample solutions were
kept under an atmosphere of argon by using rubber septa and argon-
filled balloons. In a typical binding experiment, a stock solution of
the receptor H1 (∼0.5 mM) was added in aliquots of 5-10 µL to a
solution of the ruthenium guest complex (∼5 µM) of known concentra-
tion. The increase in emission intensity at 600 nm (for excitation at
λexc ) 435 nm) was monitored as a function of host concentration.
Addition of H1 was repeated until no further increase in emission
intensity was observed.
The 1H NMR binding studies were carried out in CDCl3 or CD2Cl2
solution. In a typical experiment, the 1H NMR spectrum of the solution
of pure H1 (2 mM in 0.5 mL of CDCl3) was recorded first, and then
small aliquots (5-50 µL) of the guest stock solution in CDCl3 (25
mM, 0.2 mL) were added to the NMR tube via a gas tight syringe.
The chemical shifts of the amide protons of the host were monitored
as a function of guest concentration. Addition of guest was continued
until no further shifts in the amide protons were observed.
3,5-Bis{[6-(pivaloylamino)-2-pyridyl)amino]carbonyl}pyridine,
H1. To a solution of 0.5 g (1.43 mmol) of HP and 0.89 mL (6.4 mmol)
of triethylamine in 50 mL of anhydrous THF was added 0.35 mL (2.9
mmol) of pivaloyl chloride. After stirring at room temperature
overnight, the reaction mixture was concentrated to a sticky yellow
solid. Chromatography on silica gel using ethyl acetate/hexane (5:95)
as the eluent yielded 250 mg (34%) of H1, mp 244-245 °C: 1H NMR
(DMSO-d6) δ 1.25 (s, 18 CH3), 7.73 (m, two pyr-H-3′), 7.87 (m, four
pyr-H-4′,5′), 8.82 (s, pyr-H-4), 9.26 (m, two pyr-H-4,6), 10.84 (s, four
CONH); FAB-MS 518 (M + H)+.
Preparation of Organic Guest Molecules. 5-[4-(4′-Methyl)-2,2′-
bipyridylidene]-2,4,6-(1H,3H,5H)-pyrimidinetrione, G1. 4-(4′-Meth-
yl-2,2′-bipyridyl)carboxaldehyde (74.5 mg, 0.37 mmol) was added to
a hot slurry of 55 mg (0.39 mmol) of barbituric acid in absolute ethanol,
and the mixture was heated at reflux overnight. The light yellow
precipitate was collected via filtration, washed with hot water (to remove
unreacted barbituric acid), and then washed with absolute ethanol and
finally ethyl ether. The product was dried under vacumn overnight to
give 83.5 mg (73%) of G1 as a bright yellow powder, mp > 200 °C:
1H NMR (DMSO-d6) δ 2.50 (s, bpy-4′-CH3), 6.14 (s, CdCH-), 7.50
(d, J ) 5.5, H-5′), 7.56 (d, J ) 5.2, H-5), 8.15 (s, H-3′), 8.29 (s, H-3),
8.60 (d, J ) 5.5, H-6′), 8.68 (d, J ) 5.2, H-6), 10.23 (s, two NH);
FAB-MS 309 (M + 1)+.
Molecular Mechanics Calculations. All calculations were carried
out using the Molecular Mechanics program (MM2),36 a part of the
CAChe WorkSystem (v. 3.8), from CAChe Scientific Co.
5-[4-(4′-Methyl)-2, 2′-bipyridyl]methyl-2, 4, 6- (1H,3H,5H)-py-
rimidinetrione, G2. A slurry of 50 mg (0.16 mmol) of G1 in 10 mL
of DMF was saturated with H2 for 30 min and then was treated with
10% Pd/C. After 12 h, the reaction mixture was filtered and then
concentrated to give 32 mg (69%) of G2: 1H NMR (DMSO-d6) δ 2.40
(s, bpy-4′-CH3), 3.45 (s, CH2), 7.25 (d, J ) 4.4, H-5,5′), 8.20 (s, H-3,3′),
8.51 (d, J ) 4.4, H-6,6′), 11.11-11.25 (two NH); FAB-MS 310 (M +
H)+.
The initial structure of the host or guest moleculewas constructed
assuming that the molecule is planar in the conjugated regions. Local
minima were avoided by choosing the lowest energy configuration from
a sequential minimization by varying all the dihedral angles of the inter-
ring bonds in 12° steps. All the N-H and OdC bonds responsible for
the hydrogen bonding in the host molecule were oriented toward the
center so that the hydrogen bonding network would be intact. The
selected structure was further optimized to within 0.0003 kcal/mol.
The RuII(bpy)2 group was attached to the bipyridine side of the host
molecules, and the coordination environment of this ruthenium was
taken to be that of the crystal structure.37
Once the individual host or guest molecules were optimized, the
oxygen atom of the pivotal OdC bond in the barbiturate ring was
brought to 2Å distance from the para-H of the central pyridine of the
host molecule with CdO‚‚‚H angle of 180°. For the starting config-
uration, the 2, and 4-C’s of the barbiturate ring of the guest molecules
were placed in the same plane of the pyridine ring of the host, and the
structure was then minimized to a limit of 0.0003 kcal/mol.
Preparation of Host Moleules. 3,5-Bis{[(6-amino-2-pyridyl)-
amino]carbonyl}pyridine, HP. A slurry of 3.0 g (17.9 mmol) of 3,5-
pyridine dicarboxylic acid in 2 mL of CHCl3, 14 mL of thionyl chloride,
and a drop of DMF was heated at reflux under an inert atmosphere for
5 h, resulting in a clear orange solution. The reaction mixture was
concentrated under vacuum, and the resulting light orange solid was
washed with benzene to remove remaining thionyl chloride. The solid
was redissolved in 50 mL of CH2Cl2 and was added slowly via cannula
to a vigorously stirred solution of 8.9 g (81.5 mmol) of 2,6-
diaminopyridine in 6 mL of triethylamine and 200 mL of CH2Cl2 at 0
°C. The reaction mixture was allowed to warm to room temperature
and then was stirred for 24 h. The reaction mixture was concentrated,
and the resulting olive green solid was washed with water to remove
excess 2,6-diaminopyridine and triethylamine hydrocloride. The crude
product was purified by crystallization from tetrahydrofuran-heptane,
affording 4.5 g (72%) of H1 as a light greenish-yellow powder, mp >
200 °C (dec): 1H NMR (DMSO-d6) δ 5.83 (s, two NH2), 6.27 (d, J )
7.3, two pyr-H-3′), 7.40 (m, four pyr-H-4′,5′), 8.78 (s, pyr-H-4), 9.15
5-Ethyl, 5-[4-(4′-Methyl)-2,2′-bipyridyl]methyl-2,4,6-(1H,3H,5H)-
pyrimidinetrione, G3. Diethyl 2-ethylmalonate (0.18 g, 1 mmol) was
added to a slurry of 30 mg (1.25 mmol) of NaH in 10 mL of dry DMF.
Stirring was continued for about 30 min until a clear solution was
obtained, and then 50 mg (2 mmol) of additional NaH was added. A
solution of 0.42 g (1 mmol) of 4-bromomethyl-4′-methyl-2,2′-bipyridine
dihydrobromide in 2 mL of DMF was added dropwise. The reaction
was allowed to stir for 5 h. Water (2 mL) was added, and then the
solution was neutralized with 10% aqueous HNO3. The crude product,
4-(4′-methyl)-2,2′-bipyridyl)methyl malonate, was isolated by extraction
with CH2Cl2 followed by concentration and then silica gel chromatog-
raphy using CH2Cl2/EtOAc (8:2) as the eluant, resulting in 0.35 g (95%)
of a light yellow oil. A solution of the crude product, 60 mg (1 mmol)
of urea, and 0.6 mL of ethanolic sodium ethoxide (21% by weight) in
10 mL of absolute ethanol was heated at reflux for 2 h. Water (20
mL) was added, and the solution was acidified to pH 1 with 10%
aqueous HNO3. The resulting solution was cooled in the freezer
overnight, and the product G3 precipitated as a white crystalline solid,
0.2 g (67%), mp > 270 °C: 1H NMR (DMSO-d6) δ 0.79 (t, J ) 7.3,
CH2CH3), 2.00 (q, J ) 7.3, CH2CH3), 2.39 (s, bpy-4′-CH3), 3.22 (s,
CH2), 7.05 (d, J ) 4.3, H-5′), 7.26 (d, J ) 4.3, H-5), 8.10 (s, H-3′),
8.19 (s, H-3), 8.50 and 8.57 (two d, J ) 4.3, H-6,6′), 11.52 (s, two
NH); FAB-MS 339 (M + 1)+.
Barbituric Acid Derivatives. The 5-cinnamylidenepyrimidone-
2,4,6-(1H,3H,5H)-trione18 (BC3H3) described earlier was reduced to
BC3H6 with Pd/C (10%) as described for G1 above. The 1-[3,5-
ditrifluoromethylbenzene]methyl-2,4,6-(1H,3H,5H)-pyrimidinetrione
(BCF3) was prepared from 3,5-trifluoromethylbenzaldehyde and bar-
bituric acid, followed by reduction with Pd/C (10%) using similar
conditions to those used above for G1 and G2. Barbital was
synthesized as described previously.34 All these organic derivatives
were characterized by NMR in CDCl3.
(34) A Textbook of Practical Organic Chemistry; Vogel, A. I., Ed.; John
Wiley and Sons: New York, 1956.
(35) Cowart, M.; Sucholeiki, I.; Bukownik, R. R. Wilcox, C. S. J. Am.
Chem. Soc. 1988, 110, 6204.
(36) Allenger, N. L. J. Am. Chem. Soc. 1977, 99, 8127.
(37) Rillema, D. P.; Jones, D. S.; Levy, H. A. J. Chem. Soc., Chem.
Commun. 1979, 849.
Preparation of Ruthenium Complexes: Ru(4,4′-di-tert-butyl-
bpy)2(G1)[PF6]2, RuG1. A slurry of 19.7 mg (0.064 mmol) of G1
and 39.5 mg (0.531 mmol) of cis-Ru(4,4′-di-tert-butyl-bpy)2Cl2‚2H2O
in 5 mL of ethanol/H2O (70:30) was degassed with argon for 30 min
and then heated at reflux under an argon atmosphere for 8 h, causing

12858 J. Am. Chem. Soc., Vol. 119, No. 52, 1997
Chin et al.
the color to change from purple to bright orange. The solvent was
removed by rotary evaporation, the resulting orange solid was redis-
solved in 2 mL of water, and then a saturated aqueous solution of NH4-
PF6 was added. The resulting orange precipitate was cooled in the
freezer, filtered, and then washed with water and ethyl ether. The crude
product was purified by adsorption chromatography on a neutral
alumina column (2 × 15 cm) by using CH3CN/H2O (8:2) as the eluant,
resulting in 50 mg (60%) of the complex, RuG1: 1H NMR (DMSO-
d6): δ 1.36 (s, 36 CH3), 2.49 (s, bpy-4′-CH3), 6.02 (s, CdCH), 7.20-
7.59 (m, 12 bpy-H-3, 5), 8.25 (d, H-6′) 8.50 (s, H-6), 8.79 (s, 4
H-6′′,6′′′), 10.24 (s, two NH); Neg-FAB-MS 1235 (M - 1)+.
Ru(4,4′-di-tert-butyl-bpy)2(G2)[PF6]2, RuG2. Complex RuG2 was
prepared by two different methods. In the first method, similar to that
described for RuG1, a solution of 40 mg (0.054 mmol) of cis-Ru(4,4′-
di-tert-butyl-bpy)2Cl2‚2H2O and 20 mg (0.064 mmol) of G2 in 5 mL
of 7:3 ethanol/H2O was heated at reflux for 8 h under an argon
atmosphere. After precipitation as its PF6 salt by addition of a saturated
solution of NH4PF6, the product was purified on a neutral alumina
column by using CH3CN/H2O (95:5) as the eluant (24 mg, 60% yield).
The second method involved the catalytic hydrogenation of RuG1 in
methanol. RuG1[PF6]2 (56.7 mg, 0.056 mmol) was dissolved in 20
mL of methanol, and then the solution was saturated with H2 for 1 h.
Pd/C catalyst (10%, 30 mg) was added to the flask, and the reaction
was allowed to proceed for 22 h. The RuG2 was purified as described
for RuG1, resulting in 70% yield (∼40 mg): 1H NMR (DMSO-d6): δ
1.37 (s, 36 (CH3), 2.49 (s, 3bpy-4′-CH3), 3.31 (s, CH2), 7.20-7.59 (m,
12 bpy-H-3,5), 8.56 (s, H-6′), 8.62 (s, H-6), 8.81 (s, 4 H-4′′, 6′′′), 8.94
(s, 2 NH); Neg-FAB-MS 1237 (M - 1)+.
Ru(4,4′-di-tert-butyl-bpy)2(G3)[PF6]2, RuG3. This complex was
prepared in 60% yield as described above for RuG1: 1H NMR (CDCl3)
δ 0.93 (t, J ) 7.3, CH2CH3), 1.39 (s, 36 CH3), 2.19 (q, J ) 7.3, CH2-
CH3), 2.55 (s, bpy-4′-CH3), 3.38 (s, CH2), 7.20-7.60 (m, 12 bpy-H-
3,5), 8.01 (s, H-6′), 8.10 (s, H-6), 8.15 (m, 4 H-6′′,6′′′), 8.68 (s, 2 NH);
Neg-FAB-MS 1265 (M - 1)+.
Acknowledgment. This work was supported by the U.S.
Department of Energy, Division of Chemical Sciences, Office
of Basic Energy Sciences under contracts DE-FG05-90ER1410
and DE-FG02-93ER14356. We would also like to thank
Professor C. Wilcox for sending us an early version of his
program for the determination of binding constants by NMR.
JA971481Y