The design and synthesis of bis-[4'-azido-2,2':6',2-terpyridine platinum(II)] complexes with rigid and extended linkers for studying the topology of DNA by photoaffinity labeling

Article abstract of DOI:10.1006/bioo.1999.1152

A family of bis-[4'-Azido-2,2':6',2''-terpyridine platinum(II)] complexes with linear linkers of varying length have been synthesized. They have been designed to bis-intercalate into two DNA duplexes in close proximity, the azido groups allowing the sites of intercalation to be photoaffinity labeled. The linker to Pt(II) bonds are susceptible to cleavage by thiols and cyanide ion, which is a requirement for the intended method of analysis by 2D gel electrophoresis. (C) 1999 Academic Press.

Full text of DOI:10.1006/bioo.1999.1152

Bioorganic Chemistry 27, 477–486 (1999)
Article ID bioo.1999.1152, available online at http://www.idealibrary.com on
The Design and Synthesis of Bis-[4Ј-Azido-2,2Ј:6Ј,2Љ-Terpyridine
Platinum(II)] Complexes with Rigid and Extended Linkers for
Studying the Topology of DNA by Photoaffinity Labeling
Gordon Lowe,1 Anne-Sophie Droz, Jenny J. Park, and George W. Weaver
The Dyson Perrins Laboratory, Oxford University, South Parks Road,
Oxford, OX1 3QY, United Kingdom
Received May 27, 1999
A family of bis-[4Ј-Azido-2,2Ј:6Ј,2Љ-terpyridine platinum(II)] complexes with linear linkers
of varying length have been synthesized. They have been designed to bis-intercalate into two
DNA duplexes in close proximity, the azido groups allowing the sites of intercalation to be
photoaffinity labeled. The linker to Pt(II) bonds are susceptible to cleavage by thiols and
cyanide ion, which is a requirement for the intended method of analysis by 2D gel electro-
phoresis.
᭧ 1999 Academic Press
Key Words: bis-intercalators; photoaffinity labeling; molecular rulers; DNA topology.
INTRODUCTION
In order to study the topology of packaged DNA we have designed a family of
reagents that should cross-link two DNA duplexes in close spacial proximity. These
molecules possess four essential features:
(i) They are bis-intercalators with a rigid and extended linker. By equilibrating
them with packaged DNA (e.g., bacteriophage heads, nucleosomes, chromosomes)
they should bind to and cross-link two duplexes whose spacial relationship best
matches the geometry of the linker since this will provide the greatest binding energy.
(ii) The linker length is variable. This should allow different sets of sites in the
packaged DNA to be cross-linked.
(iii) The linker is cleavable at ambient temperature in aqueous solution at neu-
tral pH.
(iv) The intercalators carry a photoaffinity label.
The third and fourth features are required to identify the sites of intercalation using
two-dimensional gel electrophoresis. After photoaffinity labeling the DNA will be
digested with a restriction endonuclease and the fragments electrophoresed. The
1 To whom correspondence and reprint requests should be addressed. Fax: ϩ44 (0)1865 275674.
E-mail: gordon.lowe@chem.ox.ac.uk.
477
0045-2068/99 $30.00
Copyright ᭧ 1999 by Academic Press
All rights of reproduction in any form reserved.

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fragments will then be treated on the gel with the reagent to break the cross-link.
Orthogonal electrophoresis under identical conditions will ensure that those fragments
that were not cross-linked will be on the diagonal of the 2D-electrophoretogram but
those fragments that have been cleaved will generate two off-diagonal spots that can
be extracted and sequenced. In this way the sites of intercalation that were cross-
linked will be identified.
We have shown that 2,2Ј:6Ј,2Љ-terpyridine platinum(II) 4-picoline complexes are
potent intercalators of DNA and have selected this moiety for the intercalator groups
(1). The linkers provide the fourth ligand in the 2,2Ј:6Ј,2Љ-terpyridine platinum(II)
complexes and have 4-substituted pyridine groups at each end. Ethynyl and 1,4-
phenylene units are used to link the two pyridine groups in a rigid and extended
linear configuration. We established at an early stage in the study that thiols and
cynanide ion were reagents that would displace pyridine groups, e.g., in the 2,2Ј:6Ј,2Љ-
terpyridine platinum(II) 4-picoline complex in aqueous solution at ambient tempera-
ture and neutral pH. The photoaffinity labeling group is the azido group. Aryl azides
are known to generate nitrenes on photolysis (2). Such species are highly reactive
and indiscriminate in their behavior and so should react with the first bond they
encounter. For this reason they are the functional group of choice for photoaffinity
labeling (3). Since we expect the reagents to bis-intercalate DNA between helices
whose spacial relationship best matches the geometry of the bis-intercalators, the
expectation is that at least some of the DNA will become covalently cross-linked at
these sites of intercalation on photoactivation.
RESULTS AND DISCUSSION
4Ј-Azido-2,2Ј:6Ј,2Љ-terpyridine was synthesised as outlined in Scheme 1. 4Ј-Chloro-
2,2Ј:6Ј,2Љ-terpyridine reacts cleanly with anhydrous hydrazine to give 4Ј-hydrazino-
2,2Ј:6Ј,2Љ-terpyridine in good yield. It is converted almost quantitatively to 4Ј-azido-
2,2Ј:6Ј,2Љ-terpyridine by treatment with sodium nitrite in aqueous acetic acid.
The shortest linker, 4,4Ј-dipyridyl, is commercially available. 1,4-Bis(4-pyridyl)bu-
tadiyne has been reported previously and the same synthetic route was used (4).
Longer linkers were made using palladium catalysed coupling chemistry as outlined
in Scheme 2 (5).
Concern, however, that linkers with increasingly lengthy hydrophobic cores would
lack sufficient water solubility as their bis-[4Ј-azido-2,2Ј:6Ј,2Љ-terpyridine-plati-
num(II)] complexes led us to consider alternative ways of generating linear rigid
linkers. By treating trans-diamminedichloroplatinum (II) [transplatin] with 4,4Ј-dipyr-
idyl and with 1,4-bis(4-pyridyl)butadiyne), the trans-diammine bis(4,4Ј-dipyridyl)
SCHEME 1. Synthesis of 4Ј-azido-2,2Ј:6Ј,2Љ-terpyridine. Reagents: (i) anhydrous hydrazine, isobuta-
nol; (ii) NaNO2, aq. AcOH.

BIS-[4Ј-AZIDO-2,2Ј:6Ј2Љ-TERPYRIDINE PLATINUM(II)] COMPLEXES
479
SCHEME 2. Synthesis of rigid and extended linkers. Reagents: (i) Trimethylsilylacetylene, Cu2Cl2,
(Ph3P)2PdCl2, NEt3; (ii) Aq. KOH; (iii) (Ph3P)2PdCl2, Cu2I2, NHEt2, 4-bromopyridine.
platinum (II) and trans-diammine bis[1,4-bis(4-pyridyl)butadiyne]platinum(II) com-
plexes were obtained (Scheme 3). This strategy could provide very long linear linkers
by using the linkers whose syntheses are outlined in Scheme 2 if required.
The recently developed strategy for the facile platination of 2,2Ј:6Ј,2Љ-terpyridines
at ambient temperature was essential for the platination of the thermally labile 4Ј-
azido-2,2Ј:6Ј,2Љ-terpyridine (6). Using this approach and the rigid linear linkers, the
bis-(4Ј-azido-2,2Ј:6Ј,2Љ-terpyridine) platinum(II) complexes (1–4) shown in Scheme
4 have been prepared. They possess the four features adumbrated above, which are
required to study the topology of DNA.

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LOWE ET AL.
SCHEME 3. Synthesis of trans-diammine bis(4,4Ј-dipyridyl) platinum(II) dinitrate and trans-diam-
mine bis[1,4-bis(4-pyridyl)butadiyne]platinum(II) dinitrate. Reagents: (i) trans-diamminedichloroplati-
num(II), aq.AgNO3.
EXPERIMENTAL
General Methods and Materials
Thin layer chromatography was performed on aluminium sheets precoated with
neutral alumina (0.2 mm, Merck Aluminiumoxid, 60 F254) and, unless otherwise
indicated, eluted with diethyl ether. Plates were visualized under UV light and stained

BIS-[4Ј-AZIDO-2,2Ј:6Ј2Љ-TERPYRIDINE PLATINUM(II)] COMPLEXES
481
SCHEME 4. Bis-[4Ј-azido-2,2Ј:6Ј,2Љ-terpyridine platinum(II)] complexes with rigid and extended
linkers. The distance between the two nitrenes that would be generated on photoactivation are as follows
˚
˚
˚
˚
˚
(1, 28.2A), (2, 32.5A), (3, 36.8A), (4, 34.1A) and (5, 44.3A).
to detect terpyridine with FeCl2 solution (saturated solution in 1 M HCl). Melting
points were recorded on a Kofler block apparatus and are uncorrected.
Mass spectra were recorded by Dr. R. T. Aplin on a V. G. Biotech Bio-Q spectrometer
[electrospray ionisation (ESI)]; the samples were dissolved in methanol:water
(1:1 v/v). Values are quoted in m/z with only the molecular [M]+, fragments of
molecular ions, and major peaks being quoted. Routine mass spectra were obtained
on a Micromass platform APCI spectrometer. Samples were run in MeOH/CH2Cl2
(1:1). Routine proton magnetic resonance spectra were recorded at 200 MHz on a
Varian Gemini 200 spectrometer. Higher field spectra were recorded at 500 MHz by
Mrs. E. McGuinness on a Bruker AM500 spectrometer. Coupling constants (J) are
recorded in Hertz to one decimal place. Chemicals were purchased from Sigma
Chemical Co. Ltd. and Aldrich Chemical Co. and were used without further purifica-
tion. Solvents were obtained from BDH and Fisons at reagent grade and used without
distillation. Sonication was performed in equipment (Model No. SC-120TH, 220 V,
1.2 amps) supplied by Sonicor Instrument Corp. (Copiague, NY).

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LOWE ET AL.
4Ј-Hydrazino-2,2Ј:6Ј,2Љ-terpyridine
4Ј-Chloro-2,2Ј:6Ј,2Љ-terpyridine (600 mg, 2.2 mmol) was dissolved in isobutanol
(12 ml) with warming. Excess hydrazine (4 ml) was added. The mixture was then
heated to reflux under argon, with stirring, for 30 h. On cooling white crystals
precipitated out of solution. These were collected by filtration and washed with a
few drops of water to yield analytically pure 4Ј-hydrazino-2,2Ј:6Ј,2Љ-terpyridine (439
mg, 74%): m.p. 195–197ЊC; (Found: C, 68.4; H, 4.6; N, 26.6. C15H13N5 requires C,
68.4; H, 4.9; N, 26.6%);vmax (KBr)/cmϪ1 3329(w, br), 3277(s), 3181(m), 1644(w),
1605(m), 1585(s), 1565(s), 1466(m), 1403(m), 1229(w), 1069(w), 996(m), 864(m);
3
␦
(200 MHz, CDCl3) 8.69 [d, J(6,5) ϭ 4.6, 2H, H-C(6), H-C(6Љ)]; 8.63 [d,
H
3J(3,4) ϭ 8.0, 2H, H-C(3), H-C(3Љ)]; 7.87 [s, 2H, H-C(3Ј), H-C(5Ј)]; 7.86 [dt,
3J(4,5) ϭ J(4,3) ϭ 7.7, J(4,6) ϭ 1.6, 2H, H-C(4), H-C(4Љ)]; 7.34 [ddd, J(5,4) ϭ
7.4, 3J(5,6) ϭ 4.9, 4J(5,3) ϭ 1.3, 2H, H-C(5), H-C(5Љ)]; 5.81 (s, br, 1H, terpyNH.NH2);
3.83 (s, br, 2H, terpyNH. NH2); m/z (ESI) : 264.26 (100%, [MH]+).
3
4
3
4Ј-Azido-2,2Ј:6Ј,2Љ-terpyridine
A solution of 4Ј-hydrazino-2,2Ј:6Ј,2Љ-terpyridine (0.263g; 1.0mmol) in acetic acid
(2.0 ml) and water (1.0 ml) was treated dropwise at 0ЊC with a cold solution of
sodium nitrite (0.69 g; 10 mmol) in water (2.0 ml). A cream solid was precipitated.
When the addition was complete ether (20 ml) was added and the aqueous layer
made alkaline by the addition of solid sodium hydroxide beads. The solid dissolved
and the aqueous phase was further extracted with ether (2 ϫ 20 ml). The combined
organic extracts were dried and evaporated to give the title compound as a pale yellow
brown solid (0.273 g, 99%). Crystallization from methanol-dichloromethane gave
pale yellow needles mp. 140–141ЊC (Found: C, 65.7; H, 3.6; N, 30.5. C15H10N3
requires C, 65.7; H, 3.6; N, 30.6%);vmax (nujol)/cmϪ1 2109 (N3); ␦H (200MHz CDC13)
7.37 (2H, ddd, J 1.0, 4.8 and 5.9, terpy H5,5Љ),7.87 (2H, td, J 1.8, 7.8, terpy H4,4Љ),
8.16 (2H, s, terpy H3Ј,5Ј), 8.63 (2H, d, J 8.0, terpy H3,3Љ), and 8.68–8.74 (2H, m,
terpy H6,6Љ); ␦C (50MHz CDCl3) 111.1, 121.3, 124.1, 136.8, 149.1, 150.8, 155.2,
157.1; m/z (ESI): 275(MH+).
1,4-Bis(4-pyridyl)butadiyne
This was prepared by the method of Della Ciana and Haim (4) as white crystalline
plates, m.p. 208–209ЊC [lit.(4) m.p. 203–205 ЊC]. ␦H (ppm){200 MHz, CDC13}:
8.63, AAЈm, 4H, H2, H6; 7.38, BBЈm, 4H, H3, H5.
Preparation of 4,4Љ-dipyridyl-1Ј,4Ј-diethynylbenzene
1,4-Diethynylbenzene. 1,4-Bis(trimethylsilylethynyl)benzene (5) (1.00 g, 3.71
mmol) was dissolved in dichloromethane (15 ml) and methanol (15 ml). Aqueous
potassium hydroxide (1 M, 3 ml) was added dropwise with stirring. The mixture was
stirred at room temperature for 2.5 h. The organic solvent was removed under reduced
pressure. Water (25 ml) was added and the mixture was extracted with ether (3 ϫ
30 ml). The combined ether extracts were dried (MgSO4), decolorized with activated
charcoal, and the solvent was removed under reduced pressure to yield 1,4-diethynyl-
benzene (367 mg, 78%) as a white solid, which was used immediately without further

BIS-[4Ј-AZIDO-2,2Ј:6Ј2Љ-TERPYRIDINE PLATINUM(II)] COMPLEXES
483
purification, m.p. 95–96ЊC. ␦H (ppm){200 MHz, CDCl3}: 7.46, s, 4H, C6H4; 3.18, s,
2H, acetylenic H. APCI: m/z 127 (MHϩ, 14%)
4,4Љ-Dipyridyl-1Ј,4Ј-diethynylbenzene. Bis(triphenylphosphine)palladium(II) chlo-
ride (70.2 mg, 0.10 mmol) was added to a stirred suspension of 4-bromopyridine
hydrochloride (778 mg, 4.0 mmol), 1,4-diethynylbenzene (252 mg, 2.0 mmol), cop-
per(I) iodide (28.6 mg, 0.15 mmol), and dry diethylamine (15 ml) under an atmosphere
of argon. The reaction was stirred for 36 h at room temperature under argon. A further
portion of bis(triphenylphosphine)palladium(II) chloride (16.3 mg, 0.023 mmol) was
added. The reaction was stirred for a further 48 h. The mixture was filtered through
celite using ethyl acetate and concentrated under reduced pressure. The residue was
chromatographed on flash silica gel using 5% methanol/dichloromethane as eluant
and further purified by chromatography on alumina (grade IV) using 50% ethyl
acetate/petroleum ether (40–60ЊC) as eluant to yield 4,4Љ-dipyridyl-1Ј,4Ј-diethynyl-
benzene (284 mg, 51%) as a pale yellow solid, m.p. 185–203ЊC. ␦H (ppm){200 MHz,
CDCl3}: 8.64, AAЈm, 4H, H2, H6, H2Љ, H6Љ; 7.58, s, 4H, C6H4; 7.41, BBЈm, 4H,
H3, H5, H3Љ, H5Љ. APCI: m/z 281 (MHϩ, 100%).
Synthesis of 4Љ,4ٞ-Dipyridyl-4,4Ј-diethynylbiphenyl
4,4Ј-Diethynylbiphenyl. 4,4Ј-Bis(trimethylsilylethynyl)biphenyl (5) (1.04 g, 2.99
mmol) was dissolved in dichloromethane (15 ml) and methanol (15 ml). Aqueous
potassium hydroxide (1 M, 3 ml) was added dropwise with stirring. The mixture was
stirred at room temperature for 2.5 h. The organic solvent was removed under reduced
pressure. Water (25 ml) was added and the mixture was extracted with ether (3 ϫ
30 ml). The combined ether extracts were dried (MgSO4), decolorized with activated
charcoal and the solvent was removed under reduced pressure to yield 4,4Ј-diethynylbi-
phenyl (562 mg, 93%) as a white solid which was used immediately without further
purification, m.p. 167–169ЊC. ␦H (ppm){200 MHz, CDCl3} 7.57, s, 8H, 2 ϫ C6H4;
3.15, s, 2H, acetylenic H. APCI: 203 (MHϩ, 15%).
4,4Ј-Diethynyl-4Љ,4ٞ-dipyridylbiphenyl.
Bis(triphenylphosphine)palladium(II)
chloride (78.2 mg, 0.11 mmol) was added to a stirred suspension of 4-bromopyridine
hydrochloride (846 mg, 4.35 mmol), 4,4Ј-diethynylbiphenyl (440 mg, 2.18 mmol),
copper(I) iodide (29.2 mg, 0.15 mmol) and dry diethylamine (30 ml) under an atmo-
sphere of argon. The reaction was stirred for 48 h at room temperature under argon.
The mixture was filtered through celite using ethyl acetate and concentrated under
reduced pressure. The residue was chromatographed on flash silica gel using 5%
methanol/dichloromethane as eluant and further purified by chromatography on alu-
mina (grade IV) using 50% ethyl acetate/petroleum ether (40–60ЊC) as eluant to yield
4,4Ј-diethynyl-4Љ,4ٞ-dipyridylbiphenyl (310 mg, 20%) as a pale yellow solid, m.p.
205–275ЊC. ␦H(ppm){200 MHz, CDCl3} 8.63, AAЈm, 4H, H2Љ, H6Љ, H2ٞ, H6ٞ; 7.65,
s, 8H, 2 ϫ C6H4; 7.41, BBЈm, 4H, H3Љ, H5Љ, H3ٞ, H5ٞ. APCI: m/z 357 (MHϩ, 48%).
Trans-Diammine bis(4,4Ј-dipyridyl)platinum(II) dinitrate
A solution of silver nitrate (36.3 mg, 0.200 mmol) in acetone/water (1:1, 0.5 ml)
was added to a suspension of transplatin (30.0 mg, 0.100 mmol) in acetone/water
(1:1, 0.5 ml) and sonicated for 24 h. The mixture was centrifuged and the supernatant
was added to a solution of 4,4Ј-dipyridyl (31.2 mg, 0.200 mmol) in acetone (0.5 ml),

484
LOWE ET AL.
maintaining an excess of 4,4Ј-dipyridyl. The mixture was sonicated for 24 h and then
centrifuged to yield trans-diamminebis(4,4Ј-dipyridyl)platinum(II) dinitrate (64.9 mg,
97%) as a white solid. ␦H (ppm){500 MHz, DMSO} 8.90, AAЈm, 4H, H2, H6; 8.84,
AAЈm, 4H, H2Ј, H6Ј; 8.25, BBЈm, 4H, H3, H5; 7.98, BBЈm, 4H, H3Ј, H5Ј; 4.73,
b s, 6H, NH3. ESI (CV ϭ 30 V): m/z 270.8 (M2ϩ, 60%), 540.3 [(M-H)+, 33%].
Trans-Diamminebis[1,4-bis(4-pyridyl)butadiyne]platinum(II) dinitrate
A solution of silver nitrate (28.0 mg, 0.165 mmol) in acetone/water (1:1, 0.5 ml)
was added to a suspension of transplatin (24.7 mg, 0.082 mmol) in acetone/water
(1:1, 0.5 ml) and sonicated for 24 h. The mixture was centrifuged and the supernatant
was added to a solution of 1,4-bis(4-pyridyl)butadiyne (37.0 mg, 0.180 mmol) in
acetone (0.5 ml), maintaining an excess of 1,4-bis(4-pyridyl)butadiyne. The mixture
was sonicated for 24 h and then centrifuged to yield trans-diamminebis[1,4-bis(4-
pyridyl)butadiyne]platinum(II) dinitrate (64.8 mg, 85%) as a light brown solid. ␦H
(ppm) {500 MHz, DMSO}: 8.82, AAЈm, 4H, H2, H6; 8.72, AAЈm, 4H, H2Ј, H6Ј;
7.99, BBЈm, 4H, H3, H5; 7.65, BBЈm, 4H, H3Ј, H5Ј; 4.74, b s, 6H, NH3. ESI
(CV ϭ 20 V): m/z 318.7 (M2ϩ, 80%).
Synthesis of Bis-4Ј-azido-2,2Ј:6Ј,2Љ-terpyridine Platinum(II) Complexes
Bis(4-pyridyl)butadiyne bis[(4Ј-azido-2,2Ј:6Ј,2Љ-terpyridine) platinum(II)] tetrani-
trate (1). A solution of silver nitrate (36.6 mg, 0.218 mmol) in acetone/water (4:1,
0.5 ml) was added dropwise to a suspension of diiodo-1,5-cyclooctadieneplatinum(II)
(56.6 mg, 0.102 mmol) in acetone/water (4:1, 0.5 ml). The mixture was vortexed and
sonicated for a few minutes and then centrifuged. The silver iodide precipitate was
discarded. The supernatant was added to a suspension of 4Ј-azido-2,2Ј:6Ј,2Љ-terpyri-
dine (22.5 mg, 0.082 mmol) in acetonitrile (0.25 ml). The mixture was vortexed and
sonicated for a few minutes and then centrifuged. The supernatant was removed and
discarded. The pellet of the 4Ј-azido-2,2Ј:6Ј,2Љ-terpyridine platinum(II) complex was
washed with acetonitrile/ether (1:3, 2 ϫ 1.5 ml) and then dissolved in water (0.75 ml).
A solution of the 1,4-bis(4-pyridyl)butadiyne (9.0 mg, 0.044 mmol) in methanol
(0.75 ml) was added to the aqueous solution of the 4Ј-azido-2,2Ј:6Ј,2Љ-terpyridine
platinum(II) complex. The mixture was vortexed and sonicated for 15 min and allowed
to stand at room temperature for 30 min. The solution was added dropwise to ether/
acetone (1:1, 20 ml) to precipitate the complex. The mixture was centrifuged. The
pellet was washed with ether/acetone (1:1, 4 ϫ 20 ml) and then dried to yield the
desired complex (44.9 mg, 79%) as an yellow-orange solid. ␦H(ppm){500 MHz,
D2O}: 9.22, AAЈm, 4H, H2ٞ, H6ٞ; 8.45–8.40, series of multiplets, 8H, H3, H3Љ, H4,
H4Љ; 8.09, s, 4H, H3Ј, H5Ј; 8.07, BBЈm, 4H, H3ٞ, H5ٞ; 7.87, d, J 5.5 Hz, 4H, H6,
H6Љ; 7.72, m, 4H, H5, H5Љ. ESI (CV ϭ 10 V): m/z 272.0 [(M-2N2)4ϩ, 67%], 279.4
[(M-N2)4ϩ, 59%], 285.9 (M4ϩ, 100%), 337.0 {[M-Pt(N3-terpy)]2ϩ, 83%}. vmax (nujol)
2121w cmϪ1 (N3).
Bis-(4-ethynylpyridyl)-1,4-phenylene bis[(4Ј-azido-2,2Ј:6Ј,2Љ-terpyridine) plati-
num(II)] tetranitrate (2). A solution of the 4,4Љ-dipyridyl-1Ј,4Ј-diethynylbenzene
(11.8 mg, 0.042 mmol) in methanol (0.75 ml) was added to an aqueous solution of
the 4Ј-azido-2,2Ј:6Ј,2Љ-terpyridine platinum(II) complex prepared on the same scale
as above in the preparation of (1). The mixture was vortexed and sonicated for 15

BIS-[4Ј-AZIDO-2,2Ј:6Ј2Љ-TERPYRIDINE PLATINUM(II)] COMPLEXES
485
min and allowed to stand at room temperature for 30 min. A yellow precipitate
formed. The mixture was centrifuged and the pellet washed with ether/acetone (1:1,
3 ϫ 20 ml) to yield the desired complex (33.7 mg) as a yellow solid. The supernatant
was added dropwise to ether/acetone (1:1, 20 ml) to precipitate more of the complex
which was washed with ether/acetone (1:1, 4 ϫ 20 ml) and then dried to yield the
desired complex (18.6 mg) as a yellow solid. The total yield of the product was 52.3
mg (88%). ␦H(ppm){500 MHz, D2O}: 9.16, AAЈm, 4H, H2ٞ, H6ٞ; 8.44–8.41, series
of multiplets, 8H, H3, H3Љ, H4, H4Љ; 8.10, s, 4H, H3Ј, H5Ј; 8.01, BBЈm, 4H, H3ٞ,
H5ٞ; 7.91, d, J 5.6 Hz, 4H, H6, H6Љ; 7.80, s, 4H, H2,, H3,, H5,, H6,; 7.74,
m, 4H, H5, H5Љ. ESI (CVϭ10 V): m/z 291.0 [(M-2N2)4ϩ, 42%], 298.1 [(M-N2)4ϩ,
50%], 305.0 (M4ϩ, 100%), 375.1 {[M-Pt(N3-terpy)]2ϩ, 58%}. vmax (nujol) 2116w
cmϪ1 (N3).
Bis-(4-ethynylpyridyl)-4,4Ј-biphenyl
bis[(4Ј-azido-2,2Ј:6Ј,2Љ-terpyridine)plati-
num (II)] tetranitrate (3). A solution of the 4,4Ј-diethynyl-4Љ,4ٞ-dipyridylbiphenyl
(13.0 mg, 0.036 mmol) in methanol (15 ml) was added to an aqueous solution of the
4Ј-azido-2,2Ј:6Ј,2Љ-terpyridine platinum(II) complex prepared on the same scale as
above in the preparation of (1). The mixture was vortexed and sonicated for 45 min
and allowed to stand at room temperature for 30 min and then concentrated under
reduced pressure. The solution was added dropwise to ether/acetone/methanol
(65:30:5, 20 ml) to precipitate the complex which was washed with ether/acetone
(1:1, 4 ϫ 20 ml) and then dried to yield the desired complex (43.9 mg, 79%) as a
bright yellow solid. ␦H(ppm) {500 MHz, D2O}: 9.06, AAЈm, 4H, H2ٞ, H6ٞ; 8.48, t,
J 7.7 Hz, 4H, H4, H4Љ; 8.42, d, J 7.9 Hz, 4H, H3, H3Љ; 8.03, s, 4H, H3Ј, H5Ј; 8.01,
BBЈm, 4H, H3ٞ, H5ٞ; 7.88, d, J 5.8 Hz, 4H, H6, H6Љ; 7.80, m, 4H, H5, H5Љ; 7.70,
m, 8H, H2,, H3,, H5,, H6,. ESI (CV ϭ 10 V): m/z 310.1 [(M-2N2)4ϩ, 13%],
317.1 [(M-N2)4ϩ, 26%], 324.1 (M4ϩ, 100%), 413.1 {[M-Pt(N3-terpy)]2ϩ, 37%}.
vmax (nujol) 2120w cmϪ1 (N3).
Trans-diamminebis(4,4Ј-dipyridyl)platinum(II) bis[(4Ј-azido-2,2Ј:6Ј,2Љ-terpyridi-
ne)platinum(II)] hexanitrate (4). A suspension of trans-diamminebis(4,4Ј-dipyridyl)-
platinum(II) nitrate (26.6 mg, 0.040 mmol) in water/methanol (1:1, 3.0 ml) was added
to an aqueous solution of the 4Ј-azido-2,2Ј:6Ј,2Љ-terpyridine platinum(II) complex
prepared on the same scale as above in the preparation of (1). The mixture was
sonicated for 5 days at room temperature. The mixture was centrifuged. The superna-
tant was added dropwise to ether/acetone (1:1, 25 ml) to precipitate the complex.
Centrifugation yielded the crude complex as a brown solid (50.8 mg, 67%), which
dissolved in water to give a yellow solution. Purification by dissolution in hot metha-
nol/water (1:1) and re-precipitation from ether/acetone (1:1, 20 ml, repeated three
times) gave the desired complex as a pale yellow solid. ␦H {500 MHz, D2O}: 9.37,
AAЈm, 4H, H2ٞ, H6ٞ; 9.14, AAЈm, 4H, H2,, H6,; 8.43–8.42, series of multiplets,
8H, H3, H3Љ, H4, H4Љ; 8.34, BBЈm, H3ٞ, H5ٞ; 8.20, BB’m, 4H, H3,, H5,; 8.11,
s, 4H, H3Ј, H5Ј; 7.87, d, J 5.7 Hz, 4H, H6, H6Љ; 7.73, m, 4H, H5, H5Љ. ESI (CV ϭ
15 V): m/z 296.1 {[M-H]5ϩ, 47% }. ESI (CV ϭ 20 V): m/z 299.2 {[(N3-terpy)Pt(bip)-
N2]2ϩ, 63%}, 312.6 {[(N3-terpy)Pt(bip)]2ϩ, 100%}, 336.4 {[M-Pt(N3-terpy)-H]3ϩ,
33%}. vmax (nujol) 2120w cmϪ1 (N3).
Trans-diamminebis[1,4-bis(4-pyridyl)butadiyne]platinum(II) bis[(4Ј-azido-2,2Ј:6Ј,

486
LOWE ET AL.
2Љ-terpyridine)platinum(II)] hexanitrate (5). A suspension of trans-diamminebis[1,4-
bis(4-pyridyl)butadiyne]platinum(II) dinitrate (30.5 mg, 0.040 mmol) in water/metha-
nol (1:1, 3.0 ml) was added to an aqueous solution of the 4Ј-azido-2,2Ј:6Ј,2Љ-terpyridine
platinum(II) complex prepared on the same scale as above in the preparation of (1).
The mixture was sonicated for 5 days at room temperature. The mixture was centri-
fuged. The supernatant was added dropwise to ether/acetone (1:1, 25 ml) to precipitate
the complex. Centrifugation yielded the crude complex as a brown solid (69.9 mg,
90%), which dissolved in water to give a yellow solution. Purification by dissolution
in hot methanol/water (1:1) and re-precipitation from ether/acetone (1:1, 20 ml,
repeated 3 times) gave the desired complex as a pale yellow solid. ␦H {500 MHz,
D2O}: 9.21, AAЈm, 4H, H2ٞ, H6ٞ; 8.91, AAЈm, 4H, H2,, H6,; 8.44–8.41, series
of multiplets, 8H, H3, H3Љ, H4, H4Љ; 8.09, s, 4H, H3Ј, H5Ј; 8.04, BBЈm, H3ٞ, H5ٞ;
7.86, d, J 5.8 Hz, 4H, H6, H6Љ; 7.82, BBЈm, 4H, H3,, H5,; 7.73–7.70, m, 4H,
H5, H5Љ. ESI (CV ϭ 15 V): m/z 315.3 {[M-H]5ϩ, 100%}, 336.8 {[(N3-ter-
py)Pt(C14H8N2)]2ϩ, 71%}, 386.7 {[M-Pt(N3-terpy)-H]3ϩ, 88%}. vmax (nujol) 2120w
cmϪ1 (N3).
ACKNOWLEDGMENTS
The authors gratefully acknowledge support for this work from the BBSRC and EPSRC and the
Fondation Suisse d’Etudes (A-S.D.).
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