Biologically inspired phosphino platinum complexes

Article abstract of DOI:10.1016/j.inoche.2012.04.039

Platinum complexes containing phosphino amino acid and amino acid ester ligands, built upon the P^PhN^R′₂ platform, have been synthesized and characterized (P^PhN ^R′₂ = [1,3-diaza]-5-phenyl phosphacyclohexane), R' = Gly (glycine) or Gly-ester (glycine ethyl ester). These complexes were characterized by ³¹P, ¹³C, ¹H, ¹⁹⁵Pt NMR spectroscopy, and mass spectrometry. The X-ray crystal structure of one of the complexes, [PtCl₂(P^PhN^Gly-ester ₂)₂], is reported, confirming cis-square planar geometry about the platinum. These complexes provide a foundation upon which larger peptides can be attached, to allow the introduction of enzyme-like features onto small molecular catalysts.

Full text of DOI:10.1016/j.inoche.2012.04.039

Inorganic Chemistry Communications 22 (2012) 65–67
Contents lists available at SciVerse ScienceDirect
Inorganic Chemistry Communications
journal homepage: www.elsevier.com/locate/inoche
Biologically inspired phosphino platinum complexes
Avijita Jain a, Monte L. Helm b, John C. Linehan a, Daniel L. DuBois a, Wendy J. Shaw a,
⁎
a
Chemical and Materials Science Division, Pacific Northwest National Laboratory, Richland, WA 99354, United States
b
Chemistry Department, Fort Lewis College, 1000 Rim Drive, Durango, CO 8130, United States
a r t i c l e i n f o
a b s t r a c t
Platinum complexes containing phosphino amino acid and amino acid ester ligands, built upon the PPhNR′
Article history:
2
platform, have been synthesized and characterized (PPhNR′2 = [1,3-diaza]-5-phenyl phosphacyclohexane),
R' = Gly (glycine) or Gly-ester (glycine ethyl ester). These complexes were characterized by 31P, 13C, 1H,
195Pt NMR spectroscopy, and mass spectrometry. The X-ray crystal structure of one of the complexes,
[PtCl2(PPhNGly-ester2)2], is reported, confirming cis-square planar geometry about the platinum. These com-
plexes provide a foundation upon which larger peptides can be attached, to allow the introduction of
enzyme-like features onto small molecular catalysts.
Received 31 January 2012
Accepted 15 April 2012
Available online 22 May 2012
Keywords:
Amino acid complexes
Bioinspired complexes
Bioinorganic ligands
© 2012 Elsevier B.V. All rights reserved.
Organometallic complexes which combine biologically inspired li-
gands with molecular catalyst cores have received increased interest
in recent years [1–4]. In particular, amino acid derived ligands have
been a focus for several reasons, including: the potential to impart
chirality; [5–7] functional groups with which to control solubility
[8]; and the potential to enhance the water solubility of the resulting
metal complex [9,10]. Perhaps more importantly, the amino acid de-
rived ligands can impart some of the features of enzymes, nature's
catalysts which perform their respective reactions with great speed
and selectivity.
The bioinorganic ligands discussed in this paper were synthesized
using a preparation modified from Karasik and coworkers [14], by
condensation of functional phosphines with formaldehyde and
amino acids (Supporting information). Both ligands, (ligand 1, a var-
iant of which has been previously reported [14] and the newly pre-
pared ligand 2) were prepared in good yield and purity (Scheme 1).
Ligand 1 is highly soluble in water and sparingly soluble in organic
solvents, while ligand 2 was found to be soluble in organic solvents
and sparingly soluble in water. This demonstrates the solvent tunabil-
ity by a simple modification of the amino acid. Interestingly, we did
not see the formation of the 8-membered ring, PPh2NR2, often ob-
served for other amines using similar chemistry [14,15].
One approach to incorporating amino acids into metal complexes
is through attachment to phosphines [5,6]. Recent work has utilized
phosphorous and nitrogen containing macrocycles for attachment of
the amino acids. Le Goff and coworkers [11] and Jain and coworkers
[12] have incorporated non-natural amino acids into 8-membered
The synthetic route used to make PPhNR′2 amino acid containing plat-
inum complexes is shown in Scheme 2 for complexes 1a, 1b, 2a and 2b.
The complexes were prepared in reasonable yield and purity, but were
air sensitive and appear to degrade with time in solution or as a solid at
room temperature. The complex 2b (cis-[PtCl2(PPhNGly-ester2)2]) was crys-
tallized by slow diffusion of ether into a dichloromethane solution of the
metal complex, and the single crystal X-ray crystallographic data is sum-
marized in Table S1 and Fig. 1. The Pt atom is four-coordinate, bound to
the two phosphorous atoms of the PPhNGly-ester2 ligands and two chloride
ligands, and is best described as a slightly distorted square planar mole-
cule. No unusual bond lengths or bond angles were observed, with select-
ed values for complex 2b given in Table S2. The two phosphorus–carbon–
nitrogen ligand rings form chair conformations that position the two
nitrogens away from the Pt center, as observed for other 6-membered
PnNn ligands, where n=1 or 2 [16].
PR2NR′ ligands, where the terminal amine from the non-natural
2
amino acid is contained within the ring. Similarly, Karasik and co-
workers have developed 6-membered rings, or PRNR′ ligands [13],
2
however, detailed studies of these ligands bound to metals have not
been reported. Here, we report the preparation and characterization
of PPhNR′ ligands, where R′ is glycine or glycine ethyl ester (1, 2),
2
and the resulting platinum complexes (1a, 1b, 2a, 2b), and we assess
the ability of the complexes to perform as catalysts for both hydrogen
production and hydrogenation chemistries. These ligands provide a
new foundation upon which to attach larger peptides, complexes
which will allow the evaluation of the influence of the outer-
coordination sphere (the enzyme-like regions not immediately
bound to the metal) on both stoichiometric and catalytic reactions.
All of the metal complexes were characterized using 1H, 13C{1H},
31P{1H}, 195Pt{1H} NMR spectroscopy (Table 1 and Figure 2) and mass
spectroscopy. The downfield shift in the 31P resonance of the metal
complexes compared to the free ligand is indicative of metal–phos-
phine coordination. As expected, the 31P spectra of the dichloro and
dimethyl compounds consist of resonances in a ratio of 1:4:1, arising
⁎
Corresponding author. Tel.: +1 509 375 5922; fax: +1 509 375 6660.
E-mail address: wendy.shaw@pnnl.gov (W.J. Shaw).
1387-7003/$ – see front matter © 2012 Elsevier B.V. All rights reserved.
doi:10.1016/j.inoche.2012.04.039

66
A. Jain et al. / Inorganic Chemistry Communications 22 (2012) 65–67
Scheme 1. Representative synthesis: PPhNGly shown.
2
Scheme 2. Synthetic scheme of phosphino amino acid/ester metal complexes. 1a. X = Me, R = H, 1b. X = Cl, R = H, 2a. X = Me, R = CH2CH3, 2b. X = Cl, R = CH2CH3.
from a mixture of Pt isotopes, one of which has a spin of ½ (Figure 2).
The 31P resonances of the methyl complexes are shifted further
downfield than the analogous chloro complexes due to the larger
trans influence of methyl compared to chloro ligands. Consistent
with this, the complexes containing methyl groups display upfield
shifts in the 195Pt resonances (~–4500 ppm) relative to the chloro
containing complexes (−4200 to −4400 ppm) which indicate the
shielding of the platinum nucleus in these complexes.
The Pt\P coupling constants for the methyl complexes are slightly
smaller than those for the chloro complexes for a given amino acid.
Due to the larger trans influence of the methyl compared to the
chloro, the Pt\P bond is weaker (longer) in methyl complexes than
chloro complexes, consistent with literature [17]. The glycine ester
complexes (2a and 2b) display significantly larger coupling constants
compared to the glycine complexes (1a and 1b). Pt\P coupling con-
stants for cis-platinum complexes have been observed to vary widely
[16]. This could be due to the increased distortion from square planar
geometry in glycine complexes due to intra-ligand hydrogen bonding
interactions.
Repeated attempts to crystallize 1a, 1b and 2a were unsuccessful;
however, the NMR data is most consistent with cis geometry for each
of the Pt complexes. The cis geometry determined from the crystal
structure for 2b implies cis geometry for the other chloro complex
(1b), and the similar 195Pt and 31P chemical shifts support this inter-
pretation. While we were unable to obtain a crystal structure of either
of the methyl complexes, 1a or 2a, it has been observed that
dimethylplatinum species preferentially orient cis relative to one an-
other [18], particularly when starting from the cis-[PtCl2(COD)]. The
similarity in 195Pt and 31P chemical shifts of the methyl complexes
suggests that they are in the same orientation; therefore, we propose
that 1a and 2a are in a cis configuration as well.
In the preparation of 1b, the tetra-substituted species (1c),
[Pt(PPhNGly2)4]2+, was also observed as a byproduct under some circum-
stances. Attempts were made to synthesize and isolate the tetra-
substituted complex by addition of 4-fold excess PPhNGly ligand to
2
[PtCl2(COD)] (Scheme 3). The resulting yellow solid was soluble in
water and gave the expected 195Pt pentet, −4914 ppm (1JPtP =1917 Hz),
Fig. 3. The corresponding 31P NMR spectrum of this complex was very
broad (~50 ppm), possibly suggesting exchange dynamics over a very
narrow timescale. Similar attempts to prepare the tetra-substituted
[Pt(PPhNGly-ester2)4]2+ revealed this complex to be one of the prod-
ucts (1JPtP =2083 Hz) of the synthesis, but we could not isolate or
synthesize this complex with high purity. The tetra-phosphine
dicationic platinum(II) complexes display similar NMR to those
found in the literature [19–25]. There was no evidence for κ2 binding
of the ligands through both the phosphorus and the nitrogen, chela-
tion that has been observed for phosphino-pyridines [21,25]. Nor
was evidence found for the mono-cationic [ClPt(P)3]+Cl complexes
[19,20,22–25].
There was no observed catalytic activity for complex 1a for elec-
trocatalytic hydrogen production or thermal hydrogenation, and the
limited stability of the complex precluded extensive catalytic reac-
tions. However, future studies incorporating different metals or utiliz-
ing different ligand sets may result in higher stability with a potential
for catalytic activity.
The synthesis of phosphine amino acid ligands is a first step in
attaching larger peptides. Gilbertson and coworkers [26–28], as
well as others [29], have demonstrated this with the incorporation
of a series of non-natural amino acids into larger peptides. This
and similar work [30] have established the ability of catalysts built
with peptides to initiate and stabilize structure with enzyme like
hydrogen bonding networks. The ligands and metal complexes
reported here provide another route, specifically through the pep-
tide backbone, rather than the amino acid side chains, to incorporate
large peptides into homogeneous catalysts to investigate the role of
the outer-coordination sphere.
Table 1
31P{1H} and 195Pt{1H} NMR data.
31P chemical shift 195Pt chemical shift
JPPt
(ppm)
(ppm)
(Hz)
cis-[PtMe2(PPhNGly2)2] (1a)
cis-[PtCl2(PPhNGly2)2] (1b)
cis-[PtMe2(PPhNGly-ester2)2] (2a)
cis-[PtCl2(PPhNGly-ester2)2] (2b)
[Pt(PPhNGly2)4]2+ (1c)
−16.7
−23.5
−15.9
−29.1
−15.0
−10.1
−4587.2
−4214.9
−4518.0
−4393.5
−4914.9
−4948.5
1673
1915
2958
3438
1917
2083
[Pt(PPhNGly-ester2)4]2+ (2c)
Fig. 1. Crystal structure for cis-[PtCl2(PPhNGly-ester2)2] (2b).

A. Jain et al. / Inorganic Chemistry Communications 22 (2012) 65–67
67
Fig. 2. 195Pt{1H} (left) and 31P{1H} (right) NMR spectra of metal complexes, 1a (top) and 2b (bottom).
Scheme 3. Synthesis of [Pt(PPhNGly2)4]2+ metal complex.
References
[1] T. Moriuchi, T. Hirao, Acc. Chem. Res. (2010), http://dx.doi.org/10.1021/ar100022n.
[2] K. Severin, R. Bergs, W. Beck, Angew. Chem. Int. Ed. 37 (1998) 1634.
[3] A. Terron, J.J. fiol, A. Garcia-Raso, M. Barcelo-Oliver, V. Moreno, Coord. Chem. Rev.
(2007) 1973.
[4] C.M. Thomas, T.R. Ward, Chem. Soc. Rev. 34 (2005) 337.
[5] B. Breit, A.C. Lanugani, Tetrahedron-Asymmetry 14 (2003) 3823.
[6] S.R. Gilbertson, S.E. Collibee, A. Agarkov, J. Am. Chem. Soc. 122 (2000) 6522.
[7] A.M.Z. Slawin, J.D. Woollins, Q. Zhang, J. Chem. Soc., Dalton Trans. (2001) 621.
[8] A.A. Karasik, I.O. Georgiev, O.G. Sinyashin, E. Hey-Hawkins, Polyhedron 19 (2000)
1455.
[9] D. Baskakov, W.A. Herrmann, J. Mol. Catal. A: Chem. 283 (2008) 166.
[10] D.E. Berning, K.V. Katti, C.L. Barnes, W.A. Volkert, J. Am. Chem. Soc. 121 (1999) 1658.
[11] A. Le Goff, V. Artero, B. Jousselme, p.D. Tran, N. Guiller, R. Metaye, A. Fihri, S. Palacin,
M. Fontecave, Science 326 (2009) 1384.
[12] A. Jain, S. Lense, J.C. Linehan, S. Raugei, H. Cho, D.L. DuBois, W.J. Shaw, Inorg.
Chem. 50 (2011) 4073.
[13] A.A. Karasik, R.N. Naumov, R. Sommer, O.G. Sinyashin, E. Hey-Hawkins, Polyhedron
21 (2002) 2251.
[14] A.A. Karasik, I.O. Georgiev, E.I. Musina, O.G. Sinyashin, J. Heinicke, Polyhedron 20
(2001) 3321.
[15] V.G. Märkl, J., G. Y., C. Schoerner, Tetrahedron Lett. 21 (1980) 1409.
[16] C.J. Curtis, A. Miedaner, R. Ciancanelli, W.W. Ellis, B.C. Noll, M. Rakowski DuBois,
D.L. DuBois, Inorg. Chem. 42 (2003) 216.
Fig. 3. 195Pt{1H} NMR of [Pt(PPhNGly2)4] 2+ complex.
In summary, platinum metal complexes containing PPhNGly/Gly-ester
,
2
have been synthesized and characterized. The prepared ligands and
metal complexes of glycine have the potential for use in aqueous homo-
geneous catalysis, biphasic reactions and chiral chemistry, while the
esterified versions can contribute to chiral catalysis in organic phases.
Simple modification of the initial amino acid allows the introduction
of different functional groups to tune the solubility. More importantly,
these complexes allow the incorporation of larger peptides, providing
a method for facile modification of the outer-coordination sphere,
introducing features of enzymes into small molecule catalysts.
[17] J.G. Verkade, L.D. Quin, Phosphorus-31 NMR spectroscopy in stereochemical anal-
ysis, VCH Publishers, Deerfield Beach, 1987.
[18] J.S. Chatt, B. L., J. Chem. Soc. Pak. 705 (1959).
[19] G.K. Anderson, J.A. Davies, D.J. Schoeck, Inorg. Chim. Acta 76 (1983) L251.
[20] G.K. Anderson, G.J. Lumetta, Inorg. Chem. 26 (1987) 1518.
[21] A.L. Balch, R.R. Guimerans, F.E. Wood, J.C. Linehan, Inorg. Chem. 24 (1985) 2021.
[22] P. Bhattacharyya, R.N. Sheppard, A.M.Z. Slawin, D.J. Williams, J.D. Woollins, J.
Chem. Soc. Dalton, Trans. (1993) 2393.
[23] J.P. Farr, F.E. Wood, A.L. Balch, Inorg. Chem. 22 (1983) 3387.
[24] P. Nair, G.K. Anderson, N.P. Rath, Organometallics 22 (2003) 1494.
[25] P. Nair, G.K. Anderson, N.P. Rath, Inorg. Chem. Commun. 6 (2003) 1307.
[26] A. Agarkov, G., S., D. Xie, R. Pawlick, G. Starkey, S.R. Gilbertson, Biopolym. (Pept.
Sci.) 84 (2006) 48.
Acknowledgments
This work was supported by the US Department of Energy Basic
Energy Sciences, Chemical Sciences, Geosciences & Biosciences Division.
Pacific Northwest National Laboratory is operated by Battelle for the US
Department of Energy.
[27] S.R. Gilbertson, C., G., J. Kao, A. Beatty, C.F. Campana, J. Org. Chem. 62 (1997) 5557.
[28] S.R. Gilbertson, W., X., Tetrahedron 55 (1999) 11609.
[29] A.M. Porte, D.,W. A. v. d., K. Burgess, J. Org. Chem. 63 (1998) 5262.
[30] M. Gonschorowsky, M., L., M. Driess, Eur. J. Inorg. Chem. (2006) 455.
Appendix A. Supplementary material
The following items can be found in the supplemental information:
1) Synthesis and characterization of the ligands and metal complexes;
2) Experimental description of catalysis; 3) Tables of the crystal proper-
ties for complex 2b. Supplementary materials related to this article can
be found online at http://dx.doi.org/10.1016/j.inoche.2012.04.039.