Platinum(II)-glutamic acid dendrimer conjugates: Synthesis, characterization, DFT calculation, conformational analysis and catalytic properties

Article abstract of DOI:10.1016/j.ica.2017.12.022

A series of platinum(II)-L-glutamic acid dendrimer conjugates having the formula PtCl₂(5,5′-Gn(OR)-2,2′-bipyridine); Gn (n = 0, 1, 2), have been synthesized by various amide bond formation methods. The dendrimer complexes were terminated as car

Full text of DOI:10.1016/j.ica.2017.12.022

Accepted Manuscript
Platinum(II)-Glutamic Acid Dendrimer Conjugates: Synthesis, Characterization, DFT Calculation, Conformational Analysis
and Catalytic Properties
Anas Lataifeh, Heinz-Bernhard Kraatz, Firas F. Awwadi, Mohammed A.
Zaitoun, Ken Sakai
PII:
S0020-1693(17)31692-4
https://doi.org/10.1016/j.ica.2017.12.022
ICA 18056
DOI:
Reference:
Inorganica Chimica Acta
To appear in:
Received Date:
Revised Date:
Accepted Date:
5 November 2017
11 December 2017
14 December 2017
Please cite this article as: A. Lataifeh, H-B. Kraatz, F.F. Awwadi, M.A. Zaitoun, K. Sakai, Platinum(II)-Glutamic Acid Dendrimer
Conjugates: Synthesis, Characterization, DFT Calculation, Conformational Analysis and Catalytic Properties, Inorganica Chimica Acta (2017), doi: https://
doi.org/10.1016/j.ica.2017.12.022
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Platinum(II)-Glutamic Acid Dendrimer Conjugates: Synthesis,
Characterization, DFT Calculation, Conformational Analysis and
Catalytic Properties
Anas Lataifeh,*[a] Heinz-Bernhard Kraatz,[b] Firas F. Awwadi,[c] Mohammed A. Zaitoun[d]
and Ken Sakai[e,f,J]
[a]
Tafila Technical University, Department of Chemistry
Tafila 66110, JORDAN
Phone: 962 079 730 1239, E-mail: lataifeh@ttu.edu.jo
[b]
University of Toronto at Scarborough, Department of Physical and Environmental Sciences
1265 Military Trail, Toronto, Ontario, CANADA
Phone: 1 416 287 7278, E-mail: bernie.kraatz@utoronto.ca
[c]
The University of Jordan, Department of Chemistry
Amman 11942, JORDAN
Phone: 962 0798137584, E-mail: f.awwadi@ju.edu.jo
[d] Mutah University, Department of Chemistry
Karak, JORDAN
Phone: 962 779692326, E-mail: zaitoun444@yahoo.com
e
[ ] Kyushu University, Department of Chemistry
Hakozaki, Higashi-Ku, Fukuoka 812-858, JAPAN
Phone: 81 92 642 2596, E-mail: ksakai@chem.kyushu-univ.jp
[f] Kyushu University, International Institute for Carbon Neutral Energy Research (WPI-I2CNER)
744 Moto-oka, Nishi-ku, Fukuoka 819-0395, JAPAN
[J]
Kyushu University, International Research Center for Molecular Systems (IRCMS)
744 Moto-oka, Nishi-ku, Fukuoka 812-858, JAPAN
Keywords: Bioinorganic / Homogeneous catalysis / Complexes / Platinum / Dendrimers /
Hydrogen evolution

2
Abstract
A series of platinum(II)-L-glutamic acid dendrimer conjugates having the formula PtCl2(5,5'-
Gn(OR)-2,2'-bipyridine); Gn (n = 0, 1, 2), have been synthesized by various amide bond formation
methods. The dendrimer complexes were terminated as carboxylic acid (R = H) or methyloxy ester
(R = Me). The complexes were characterized by mass spectrometry, elemental analysis, UV-vis,
1
1
FTIR, H-, 13C-NMR, H-TOCSY, HSQC. The G1(OH) complex aggregate in solution and solid
state, giving rise to a rigid conformation for the glutmaic acid side chain. The G2(OH) exists in the
“monomeric” form with several conformations for the glutamic acid side chains. Complexes
terminated with carboxyl group (R = H) were active catalyst toward hydrogen gas (H2) production
by photo-induced splitting of water. The turnover frequency (TOF) for the G1(OH) (14.7×1015 s–1)
exhibited a ~2-fold enhancement in H2 production compared to the unmodified parent catalyst
G0(OH) (TOF = 7×1015 s–1). While G2(OH) displayed a lower hydrogen activity (TOF = 3.8×1015
s–1) compared to G0(OH). The platinum-glutamic acid dendrimer conjugates showed a correlation
between H2 evolution activity and their ability to form aggregates, which driven by the steric
hindrance of the peptide residues in the vicinity of Pt-center.

3
Introduction
The Chemistry of platinum(II) complexes have attracted considerable attention for many years in
part due to their applications in the fields of organic light emitting devices (OLEDs),[1] cancer
therapy,[2, 3] and catalytic processes.[4, 5] Most of the reported studies on platinum(II)-peptide
conjugates were examined for their antitumor activity,[2, 6] and only few examples have discussed
their catalytic properties.[7, 8] To rationalize some of the functional and structural properties of
naturally occurring redox metalloproteins,[9, 10] amino-acid conjugates containing redox active
transition metal center (e.g. Ni, Co) have been exploited.[11, 12] In these studies the peptide
scaffolds were based on non-natural amino acids, moreover, the exact peptide structure around the
active core is quite unknown. The latter issue is of special interest due to the fact that the amino
acids, which lie in close proximity to the active site of metalloproteins, play key role in regulating
and enhancing enzyme activity.[13] Accordingly, and for all of the above examples and limitations,
we were motivated to synthesize a series of new platinum(II)-centered peptide dendrimer
conjugates and to study their catalytic activities toward photoinduced hydrogen evolution from
water. The Pt-peptide conjugate structure-activity relationship has been addresed.
Among various reported molecular catalysts for hydrogen evolution from water,[12, 14-17]
platinum(II)-based molecular catalysts were quite unique due to their applicability as catalysts for a
well-known photo-system consisting of tris(2,2'-bipyridine)ruthenium(II) ([Ru(bpy)3]2+),
methylviologen (MV2+, N,N'-dimethyl-4,4'-bipyridinum) cation and ethylenediaminetetracetic acid
disodium salt (Na2EDTA).[16] The hydrogen evolution from water in such system proceeded as a
dark reaction in the presence of platinum(II)-based molecular catalysts.[16] Furthermore,
mechanistic studies revealed that hydrogen evolution reaction is likely to proceed via the formation
of hydridoplatinum(III) intermediate (Pt(II) + H+ + e- → Pt(III)-H).[18] In these studies, the
PtCl2(bpy) complex, bpy = 2,2'-bipyridine, has been often employed as an H2-evolving center.
Peptide dendrons based on natural L-glutamic acid are well known in literature.[19] The dendron
size (peptide layers), dendron structure (open vs. backfolded) and surface functionality were
controllable. The L-glutamic acid dendron conjugates to ferrocene and Pd-porphyrin core were
reported.[20, 21] The electron and substrate transfer properties in L-glutamic acid dendron were
realized. Therefore, the coupling of L-glutamic acid peptide dendrons to PtCl2(bpy) complex
generate a synthetic molecular model, in which the peptide environment arround the H2-production
center mimics those in metalloproteins.
Herein, we report the detailed synthetic procedures, physical properties and conformational analysis
of new platinum(II)-L-glutamic acid dendrimer conjugates having the general formula [PtCl2(5,5'-
Gn(OR)-2,2'-bpy)], n (generation number) = 0, 1, 2; R = H (peripheral group = carboxylic acid), R
= Me (peripheral group = methoxyester), Figure 1a. The catalytic activity of PtCl2(5,5'-Gn(OR)-

4
2,2'-bpy) peptide conjugates toward hydrogen evolution from water was correlated to the peptide
dendrimer structure adopted by each dendrimer generation, Figure 1b.
Methods and Materials
Experimental Section
General Remarks: H2N-Glu(OMe)-OMe·HCl,[22] and Boc-Glu(OH)-OH,[23] were prepared by a
modified procedure from H2N-Glu(OH)-OH (Aldrich), thionyl chloride (SOCl2) (Alfa Aesar) and
di-tert-butyl dicarbonate (Boc2O) (Advanced ChemTech), respectively. 1-ethyl-3-(3-
dimethylaminopropyl)carbodimide hydrochloride (EDC·HCl) and 1-hydroxybenzotriazole
monohydrate (HOBt·H2O), ethylenediaminetetracetic acid disodium salt (EDTA),
dimethylsulfoxide (DMSO) and 5,5•-dimethyl-2,2•-bipyridine were obtained from Advanced
ChemTech. cis-PtCl2(DMSO)2, [MV](NO3)2 and [Ru(bpy)3](NO3)2·3H2O were prepared as
previously described.[24] The K2PtCl4 was received from Tanka Kikinzaku Kogyo. All other
reagents were purchased in their highest quality available. Pure water of high resistivity (18.2 MΩ)
was obtained by Millipore water system (Millipore Corporation). All syntheses were carried out in
air unless otherwise stated. Deuterated chloroform (CDCl3) (Sigma-Aldrich) was stored over
molecular sieves (8–12 mesh; 4Å effective pore size; Fisher) under inert atmosphere. Deuterated
[D6] DMSO ampoule (1 mL) obtained from Sigma-Aldrich.
Instrumentation and Methods: The mass spectrometry measurements were carried out on
Finnigan MAT 8400 and Bruker Apex IV time-of-flight mass spectrometry (TOF-MS). UV–Vis
and VT-UV-vis measurements were recorded using Shimadzu (UV-1800) spectrophotometer. The
VT-UV-vis measurments were performed in 5 mM aqueous NaCl solution.
The NMR spectra were recorded on a Varian INOVA 600 MHz spectrometer using a 5 mm z-
gradient triple resonance inverse HCX probe, operating at 600.23 MHz (1H) and 150.78 MHz (13C)
1
at 24 1 ºC. The H NMR spectra were recorded with a 45º pulse angle, spectral width 9590 Hz
and 128 scans. The data were reported as follows: the chemical shifts were referenced to the
residual in CDCl3 and [D6] DMSO on the δ scale (ppm), integration, multiplicity (s, singlet; d,
doublet; ddd, douplet of douplet of douplets; t, triplet and m, multiplet), coupling constants (Hz)
and 2D TOCSY (Total Correlation Spectroscopy). The TOCSY spectra were obtained with 2 scans
for each 200 t1 increments. A spectral width of 9593.5 Hz was used in both dimensions with
mixing time of 80 ms and a relaxation delay of 1.0 s. Zero filling was applied to give a final matrix
of 1×1 K. 13C NMR spectra were recorded with a 90º pulse angle, 2s relaxation delay and a spectral
width 9590 Hz. Chemical shifts were in on the δ scale (ppm) and referenced to the residues present

5
in CDCl3 and [D6] DMSO. Gradiant phase 2D HSQC experiments were performed with 2 scans
for each of 256 t1 increments and relxation delay of of 1.0s. The 1H spectral width was 9590 Hz and
the 13C spectral width was 31658.1 Hz. The NMR experimens of the Pt-complrxes (in DMSO) were
carried out within very short period of time after the NMR solution mixture had been made, this to
avoid any possible hydrolysis of the chlorido ligands
Fourier transform infrared spectroscopy (FTIR) spectra were recorded on Nicolet Impact 400 FTIR
spectrophotometer (Nicolet Analytical Instrument) using KBr pellets at 2.0 cm–1 resolution. The IR
results were reported as: s, strong; bar, broad; w, week. Melting point measurements were recorded
using Brenstated Electrothermal apparatus. Photoluminesence data were obtained under the
continuous Xe lamp (150 W) excitation in a John Yvon Fluoromax P spectrofluorometer at room
temperature for the acid terminated Pt-complexes: 1, 5, 7.
Elemental analysis was carried out on a Leeco CHNS-932 Elemental Analyzer at the institute of
organic chemistry and macromolecular chemistry, Friedrich Schiller-University of Jena. Elemental
analyses have been carried out only for Pt-complexes: 1, 4, 5, 6, 7.
DFT calculation: The molecular structures of the conjugates were optimized at DFT/B3LYP level
using Gaussian 09 package.[25] cc-pvdz basis sets are assigned to C, H, N, and Cl and LANL2DZ
to Pt. The UV-Vis spectra of 1 and 5 and their molecular orbital analysis were carried out using
Gaussian 09 and GaussSum 3 programs.[26] Time dependent density TD-DFT was used to
calculate the UV-Vis spectra in water. Conductor-like Polarizable Continuum Model (CPCM) was
used as solvation model.
Hydrogen evolution study: Photochemical hydrogen production from water was analyzed by using
an automatic H2 monitoring system. In this system, continuous flow of Ar (10.0 ml/min, controlled
by a STEC SEC-E40/PAC-D2 digital mass flow controller) was bubbled through a photolysis
solution (10 ml) contained in a cylindrical shaped, Pyrex glass vial (30 ml). The vent gas from the
vial was introduced into a 6-way valve which allowed the automatic injection of the sample gas
onto a gas chromatograph (Shimadzu GC-14A equipped with a Molecular Sieve 5A column of 2 m
x 3 mm I.D., and thermostated at 30 ºC).
The injection of the sample gas and the output signal from the thermal conductivity detector of the
gas chromatograph were both controlled by the a control software. Photolysis solutions were stirred
continuously and irradiated after deaerateding with Ar for at least 30 min prior to the photolysis.
The photoirradiation was carried out by an Ushio xenon short arc lamp UXL500D-O (operated at
350 W, 550 > λ > 240 nm). Photolysis vial was immersed in a water bath thermostated at 20 ºC to
remove IR radiation and to eliminate the temperature effect. The optical path between the
photolysis solution and the Xe lamp were always given by Pyrex glass.

6
The photolysis solution contains aqueous acetate buffer (30 mM CH3COOH/70 mM CH3COONa,
pH = 5.0, 10 mL) containing 30 mM EDTA, 0.04 mM [Ru(bpy)3](NO3)2·3H2O, 2 mM [MV](NO3)2
and 100 mM NaCl in the presence of either 1 (0.5530 mg), 5 (0.8140 mg) or 7 (1.3070 mg) at a
concentration of 0.1 mM. Sodium chloride salt was added to preclude hydrolysis of chlorido ligands
in complexes 1, 5 and 7.[28] . The initial very short induction period (ca. 5 min) is consistent with
the time required to obtain a blue photolysis solution, at the end of which the MV·+ concentration is
maximized. The photolysis was carried out under argon atmosphere for ~ 5 hr. The calculation of
the turnover frequency (TOF, H2 molecule/sec) was based on the total number of hydrogen gas
molecules produced over 5 hours.
Syntheses:
Synthesis of 2,2′-bpy-5,5′-dicarboxylic acid (dcbpy) ligand:[24] A suspension of 5,5′-dimethyl-2,2′-
bpy (1.51 g, 8.2 mmol) was dissolved in 100 mL water. Solid KMnO4 (8.57 g, 54.2 mmol) was
added to the initial suspension. Then, the reaction mixture was stirred and heated up to 80–85 ºC for
24 h. The deep black solution was cooled to r.t. and filtered off using frit funnel; the aqueous phase
was then neutralized with concentrated HCl, resulting in the formation of white suspension. The
solid was then filtered under vacuum. The white powder was collected and dried in vacuum
desiccators. Yield: 1.33 g, 54 %. 1H NMR (600 MHz, [D6] DMSO): δ = 9.29 (s, 2H, 6,6’-bpy), 8.57
(m, 2H, 3,3’-bpy), 8.45 (m, 2H, 4,4’-bpy).
Synthesis of Pt(dcbpy)Cl2 (1):[24] The cis-PtCl2(DMSO)2 (0.1060 g, 0.25 mmol) was dissolved in
methanol (20 mL) followed by addition of solid 5,5'-dicarboxylic acid-2,2'-bpy (dcbpy) (0.0490 g,
0.20 mmol). The resultant suspension was sealed in a pressure-resistant vial and reacted at 120 °C
for 6 h. Upon cooling the vial, bright yellowish-orange crystals were formed. The crystals were
filtered off and washed several times with cold acetone. To remove trace impurities, the product
was purified by recrystallization from hot ethanol/water mixture. The collected crystals were dried
in a vacuum desiccator. Yield: 0.04, 44%. M.p. = 383 °C (decomp.). TOF MS ESI– (1:1 (v/v),
CH3OH, H2O): m/z = 508.9715 [M–H]–1 calc. for C12H7N4O4PtCl2 requires 509.1789. IR (KBr, cm–
1): 3055 (br, O–H), 1700 (s, COacid), 1605 (s, C=Caromatic), 1290 (s, C–O). 1H NMR (600 MHz, [D6]
DMSO): δ = 9.99 (s, 2H, 6,6’-bpy), 8.80 (m, 2H, 4,4’-bpy), 8.78 (m, 2H, 3,3’-bpy). 13C NMR
(150.78 MHz, DMSO-d6): δ = 166.2 (COacid), 157.6 (C6,6'), 150.6 (C2,2'), 138.9 (C5,5'), 127.5 (C4,4'),
121.5 (C3,3'). UV-vis (H2O, λmax (nm): 258 (C=O), 318, 333 (bpy), 370 (MLCT). Anal. Calcd.for
C12H8Cl2N2O4Pt: C 28.25, H 1.58, N 5.49; found C 28.02, H 1.51, N 5.39.
Synthesis of 5,5′-bis(chlorocarbonyl)-2,2′-bpy:[24] A suspension of 2,2′-bpy-5,5′-dicarboxylic acid
(3.50 g, 11.6 mmol) in SOCl2 (9.0 mL, 124.0 mmol) was stirred at r.t. under Ar atmosphere. 1-2

7
drops of N,N′-dimethylformaide (DMF) was added to enhance solubility of the dcbpy ligand. The
reaction was heated up to 40 ºC. After several hours, chunks of dcbpy were still insoluble in SOCl2.
To ensure complete solubility, a 10 mL of tetrahydrofuran (THF) was added. The heating was
continued for a total of 6 hr. The solution was cooled down to r.t. and the excess SOCl2 was
removed by rotary evaporator. The red colored residue was suspended in hexane, and after
sonication for 5 min, the solution was filtered off, the orange powder was collected and dried in
1
vacuum desiccator. Yield: 3.25 g, 99.7%. H NMR (600 MHz, [D6] DMSO): δ = 9.20 (s, 2H, 6,6'-
bpy), 8.56 (m, 2H, 4,4'-bpy), 8.47 (m, 2H, 3,3'-bpy). 13C NMR (150.78 MHz, [D6] DMSO): δ
=169.1 (CO-bpy), 155.0 (C5,5'), 152.3 (C2,2'), 140.2 (C6,6'), 135.2 (C4,4'), 127.0 (C3,3').
Synthesis of 5,5′-[Glu[G1](OMe)-OMe]2-2,2′-bpy (2): 5,5′-bis(chlorocarbonyl)-2,2′-bpy (0.28 g,
1.0 mmol) was dissolved in 10 mL dry CH2Cl2. In a separate flask, a dichlormethane (CH2Cl2)
solution (20 mL) containing H2N-Glu[G1](OMe)-OMe·HCl, (0.47 g, 2.20 mmol) is mixed with dry
triethylamine (Et3N) (0.33 mL, 2.5 mmol) and stirred for 15 min at r.t.. The former solution was
added dropwise to the latter solution. After 12 hours, stirring at r.t., the solution was worked up
using saturated NaHCO3 (50 mL), 10% citric acid solution (50 ml), saturated sodium hydrogen
carbonate (NaHCO3) (50 ml) and finally with distilled water (50 mL). The organic phase was dried
over anhydrous sodium sulfate (Na2SO4), filtered and the solvent was evaporated to dryness. Pure
compound of 2 was obtained by recrystallization from hexane. Yield: 0.21 g, 38%. TOF MS ESI+
(CH2Cl2): m/z = 581.3207 [M+Na]+ calc. for C26H30N4O10Na requires 581.5269. 1H NMR (600
MHz, CDCl3): δ = 9.11 (s, 2H, 6,6′-bpy), 8.53 (s, 1H, 4,4′-bpy), 8.50 (s, 1H, 4,4′-bpy), 8.26 (d, J1,3
= 2.31 Hz, 1H, 3,3′-bpy), 8.23 (d, J1,3 = 2.31 Hz, 1H, 3,3′-bpy), 7.47 (d, J1,3 = 7.25 Hz, 2H, NH-
Glu), 4.83 (ddd, J1,3 = 7.58, 4.95, 2.64 Hz, 2H, αCH Glu), 3.81 (s, 6H, αCHCOOCH3), 3.69 (s, 6H,
γCH2COOCH3), 2.53 (m, 4H, γCH2 Glu), 2.33 (m, 2H, βCH2 Glu), 2.22 (m, 2H, βCH2 Glu). 13C
NMR (150.78 MHz, CDCl3): δ = 174.1, 172.3 (COester), 165.4 (COamide), 157.7 (C6,6′), 148.3 (C5,5′),
136.0, 129.4 (C3,3′), 121.3 (C2,2′), 53.4 (αCH Glu), 52.7, 52.5, 52.0 (COOCH3), 30.2 (γCH2 Glu),
26.6 (βCH2 Glu).
Synthesis of 5,5′-[Glu[G2](OMe)-OMe]2-2,2′-bpy, (3): 5,5′-bis(chlorocarbonyl)-2,2′-bpy (0.28 g,
1.0 mmol) was dissolved in 10 mL dry CH2Cl2. In a separate flask, a CH2Cl2 solution (20 mL)
containing Boc-Glu[G2](OMe)-OMe (1.24 g, 2.20 mmol) was mixed with 1:1 (v/v) trifluroacetic
acid (TFA), CH2Cl2 solution to remove the Boc protecting group. After 30 min, the resulting
solution was neutralized with Et3N. The solution containing 5,5′-bis(chlorocarbonyl)-2,2′-bpy was
added dropwise to H2N-Glu[G2](OMe)-OMe. After 12 hr, the solution was worked up as described
above. Pure compound of 3 was obtained by recrystallization from hexane. Yield: 0.45 g, 40 %.

8
1
TOF MS ESI+ (MeOH): m/z = 1131.2257 [M]+ calc. for C50H66N8O22 requires 1131.0994. H NMR
(600 MHz, CDCl3): δ = 9.11 (s, 2H, 6,6′-bpy), 8.54 (d, J1,3 = 8.24 Hz, NH-Glu), 8.21 (m, 2H, 4,4′-
bpy), 8.07 (d, J1,3 = 8.57 Hz, 1H, NH-Glu), 7.46 (m, 2H, 3,3′-bpy), 7.22 (d, J1,3 = 5.61, 2H, NH-
Glu), 7.12 (m, 2H, NH-Glu), 4.70 (m, 4H, αCH Glu), 4.56 (m, 1H, αCH Glu), 4.34 (m, 1H, αCH
Glu), 3.79 (s, 12H, αCHCOOCH3), 3.70 (s, 12H, γCH2COOCH3), 2.48 (m, 10H, γCH2 Glu), 2.31
(m, 9H, γCH2 and βCH2 Glu), 2.03 (m, 5H, βCH2 Glu). 13C NMR (150.78 MHz, CDCl3): δ = 173.9,
173.6, 173.5, 173.2, 173.1, 173.0, 172.7 (COesters), 170.6 170.4 (CO amide), 162.1, 161.6 (CO
amide proximal to bpy), 157.1, 156.5 (C6,6′), 118.7, 117.7 (C5,5′), 114.4, 113.5 (C3,3′), 110.9 (C2,2′),
52.7, 52.6, 52.5, 52.4 (αCH Glu), 51.5 (COOCH3), 31.4, 31.3 30.0, 29.9, 29.7, 29.6 (γCH2 Glu),
28.3, 27.9 26.3, 26.2 (βCH2 Glu).
Synthesis of [(5,5′-[Glu[G1](OMe)-OMe]2-2,2′-bpy)PtCl2] (4): Compound 2 (0.1327 g, 0.24 mmol)
was suspended in 30 mL ethanol. In a separate flask, K2PtCl4 (0.0986 g, 0.24 mmol) is dissolved in
150 mL of water. Then, the latter solution acidity was adjusted to pH = 2.5 with 1M HCl. The two
solutions were mixed, and the resultant mixture is refluxed for 4 hrs, the solution color turnd from
orange into yellowish-green. After cooling the reaction mixture, the green precipitate was collected
by filtration, and washed with cold water (20 mL) and diethylether (100 mL). To remove trace
impurities, the complex was crystallized from hot methanol. The solid was dried in vacuum
desiccator. Yield: 0.45 g, 55%. M.p. = 244°C (decomp.). TOF MS ESI+ (1:1 (v/v) CH3OH, H2O):
m/z = 824.3464 [M]+ calc. for C26H30N4O10PtCl2 requires 824.5212. IR (KBr, cm–1): 3450 (br,
amide A (non H-bonded)), 3305 (s, amide A (H-bonded)), 1740 (s, COester), 1648 (s, amide I), 1545
1
(s, amide II), 1210 (w, C–O). H NMR (600 MHz, [D6] DMSO): δ = 9.89 (s, 2H, 6,6′-bpy), 9.39
(d, J1,3 = 7.25 Hz, 2H, NH-Glu), 8.82 (m, 4H, 4,4′-bpy and 3,3′-bpy), 4.54 (m, 2H, αCH Glu), 3.69
(s, 6H, αCHCOOCH3), 3.60 (s, 6H, γCH2COOCH3), 2.55 (m, 4H, γCH2 Glu), 2.11 (m, 4H, βCH2
Glu). 13C NMR (150.78 MHz, [D6] DMSO): δ = 172.9, 171.8 (COester), 163.1 (COamide), 158.4
(C6,6′), 148.4 (C2,2′), 138.7 (C5,5′), 132.5 (C4,4′), 124.7 (C3,3′), 53.7 (αCH Glu), 52.2, 51.4
(COOCH3), 29.8 (γCH2 Glu), 25.6 (βCH2 Glu). UV-vis (H2O, λmax (nm): 298 (C=O), 344 (bpy),
438 (MLCT). Anal. Calcd.for C26H30Cl2N4O10Pt: C 37.87, H 3.67, N 6.80; found C 37.83, H 3.62,
N 6.74.
Synthesis of [(5,5′-[Glu[G1](OH)-OH]2-2,2′-bpy)PtCl2] (5): Compound 2 (0.2108 g, 0.38 mmol)
was suspended in 30 mL ethanol. Solid NaOH (0.6040 g, 1.51 mmol) is dissolved in 1 mL of
water, and then is added to the former solution. The mixture was left for 30 min to ensure complete
removal of ester group (OMe) from the dendrimer peripherals in 2. Then, the solution acidity was
adjusted to pH = 2.5 using 1M HCl. In a separate flask, the K2PtCl4 (0.1566 g, 0.38 mmol) is

9
dissolved in 150 mL of water. The solution acidity was adjusted to pH = 2.5 with 1M HCl. The two
solutions were mixed and the resultant mixture was refluxed for 4 hrs, the solution color changed
from light yellow to yellowish-green. After cooling the reaction mixture, the solution pH was
adjusted to 5. The readly formed precipitate was collected by filtration, and washed with cold water
(20 mL) and diethylether (100 mL). To remove trace impurities, the solid was crystallized from hot
ethanol/water mixture. The solid was dried in vacuum desiccator. Yield: 0.08 g, 31%. M.p. = 210°C
(decomp.). TOF MS ESI– (1:1 (v/v) of CH3OH and H2O): m/z = 767.3202 [M–H]– calc. for
C22H21N4O10PtCl2 requires 767.4069. IR (KBr, cm–1): 3450 (s, amide A (non H-bonded)), 3290 (s,
amide A (H-bonded)), 3055 (w, O–H), 1720 (s, COacid), 1650 (s, amide I), 1550 (s, amide II), 1220
1
(s, C–O). H NMR (600 MHz, [D6] DMSO): δ = 12.62 (br, 4H, COOH), 9.90 (s, 2H, 6,6′-bpy),
9.35 (d, J1,3 = 8.20 Hz, NH-Glu), 8.85 (m, 2H, 4,4′-bpy), 8.39 (m, 2H, 3,3′-bpy), 4.44 (m, 2H, αCH
Glu), 2.41 (m, 3H, γCH2 Glu), 2.13 (m, 3H, γCH2 and βCH2 Glu), 2.00 (m, 2H, βCH2 Glu). 13C
NMR (150.78 MHz, [D6] DMSO): δ = 174.6, 174.0 (COacid), 172.9 (COamide), 163.0 (C6,6′), 147.3
(C2,2′), 138.8 (C5,5′), 132.6 (C4,4′), 124.8 (C3,3′), 54.8 (αCH Glu), 30.4, 29.0 (γCH2 Glu), 25.8, 24.6
(βCH2 Glu). UV-vis (H2O, λmax (nm): 267 (C=O), 323, 336 (bpy), 390 (MLCT). Anal. Calcd.for
C22H22Cl2N4O10Pt: C 34.39, H 2.89, N 7.29; found C 34.08, H 2.78, N 7.13
Synthesis of [(5,5′-[Glu[G2](OMe)-OMe]2-2,2′-bpy)PtCl2] (6): A suspension of 3 (0.0817 g, 0.07
mmol) and cis-PtCl2(DMSO)2 (0.0382 g, 0.09 mmol) in 20 mL methanol was sealed in a pressure-
resistant vial and reacted at 120 °C for 6 hr. After the vial was cooled down to r.t.. The yellow
precipitate was collected by filtration, and then washed with cold acetone (20 mL) and diethylether
(100 mL). To remove trace impurities, the complex was crystallized from hot methanol. Finally, the
solid residue was freeze-dried affording 6 as yellow powder. Yield: 0.04 g, 38%. M.p. = 204°C
(decomp.). TOF MS ESI+ (CH3OH): m/z = 1397.2834 [M]+ calc. for [C50H66Cl2N8O22Pt]+ requires
1397.3316. IR (KBr, cm–1): 3455 (br, amide A (non H-bonded)), 3260 (s, amide A (H-bonded)),
1
1745 (s, COester), 1651 (s, amide I), 1552 (s, amide II), 1212 (w, C–O). H NMR (600 MHz, [D6]
DMSO): δ = 9.99 (s, 2H, 6,6′-bpy), 9.53, 9.80 (m, 2H, NH-Glu), 8.82 (m, 2H, 4,4′-bpy), 8.25 (m,
2H, 3,3′-bpy), 4.51 (m, 2H, αCH Glu), 3.71 (s, 12H, αCHCOOCH3), 3.62 (s, 12H, γCH2COOCH3),
2.39–2.52 (m, 12H, γCH2 Glu), 2.15–1.82 (m, 12H, βCH2 Glu). 13C NMR (150.78 MHz, [D6]
DMSO): δ =173.5, 173.0, 172.6, 169.9 (COester and amide), 161.7, 161.2 (COamide proximal to bpy), 156.5,
156.0 (C6,6′), 118.3, 117.2 (C5,5′), 113.9 (C3,3′), 112.9 (C2,2′), 52.1 (αCH Glu), 51.0, 45.0 (COOCH3),
30.9, 29.5 (γCH2 Glu), 27.5, 25.8 (βCH2 Glu). UV-vis (H2O, λmax (nm): 298 (C=O), 344 (bpy).
Anal. Calcd.for C50H66Cl2N8O22Pt: C 42.98, H 4.76, N 8.02; found C 42.73, H 4.93, N 7.90.

10
Synthesis of [(5,5′-[Glu[G2](OH)-OH]2-2,2′-bpy)PtCl2] (7): A suspension of 3 (0.1131 g, 0.10
mmol) in 1 mL methanol was allowed to react with an aqueous solution (1 mL) of NaOH (0.0320 g,
0.80 mmol) for 30 min at r.t. The solution pH was adjusted to 2.5 with 1 M HCl. The resulting
solution was transferred to a pressure-resistant vial containing cis-PtCl2(DMSO)2 (0.0.0530 g, 0.13
mmol) in methanol (20 mL). The solution was heated up to 120 °C for 6 hr. After the vial was
cooled down to r.t., the solution pH was adjusted to 3. The yellow precipitate was collected by
filtration, and then washed with cold acetone (20 mL) and diethylether (100 mL). Purification of 7
was carried out by crystallization from hot ethanol/water mixture. The resulting residue was freeze-
dried affording 7 as yellow powder. Yield: 0.03 g, 27%. M.p. = 147°C (decomp.). TOF MS ESI–
(CH3OH/H2O): m/z = 653.3040 [M–3H+Na]2- calc. for [C42H47Cl2N8NaO22Pt]2- requires 653.4189.
IR (KBr, cm–1): 3480 (s, amide A (non H-bonded)), 3260 (s, amide A (H-bonded)), 3065 (w, O–H),
1
1725 (s, COacid), 1650 (s, amide I), 1545 (s, amide II), 1214 (s, C–O). H NMR (600 MHz, [D6]
DMSO): 9.87 (s, 2H, 6,6′-bpy), 9.80, 9.49 (d, J1,3 = 7.45 Hz, 2H, NH-Glu), 8.90, 8.79 (m, 2H, 4,4′-
bpy), 8.41, 8.30 (m, 2H, 3,3′-bpy), 8.14 (m, 4H, NH-Glu), 4.50–4.18 (br m, 6H, αCH Glu), 3.30,
2.25 (m, 12H, γCH2 Glu), 2.08–1.92 (m, 12H, βCH2 Glu). 13C NMR (150.78 MHz, [D6] DMSO):
174.2, 174.0, 169.7, 169.2 (COester and amide), 161.4, 161.0 (COamide proximal to bpy), 155.8 (C6,6′), 145.8
(C2,2′), 119.2 (C5,5′), 117.3 (C4,4′), 113.0 (C3,3′), 54.0 (αCH Glu), 31.1, 30.2 (γCH2 Glu), 27.7, 26.0
(βCH2 Glu). UV-vis (H2O, λmax (nm): 265 (C=O), 320, 334 (bpy), 390 (MLCT). Anal. Calcd.for
C42H50Cl2N8O22Pt: C 39.26, H 3.92, N 8.72; found C 38.98, H 3.96, N 8.67.
Results and discussion
Design principles: The platinated peptide dendrimer conjugates designed in this report, shown in
Fig. 1a, were of generation 1 (G1(OH), 5) and generation 2 (G2(OH), 7). In addition, the parent
complex (G0(OH), 1) was prepared as a control to ensure the effect of tethering the peptide
residues. The photo-system used to induce water reduction to molecular hydrogen by catalyst 1, 5
and 7 is shown in Figure. 1b.

11
Figure 1. (a) Molecular Pt(II) complexes: The PtCl2(5,5'-(COOH)-2,2'-bpy) (1, G0(OH)), the glutamic acid dendron in 5
(G1(OH)) is of generation 1 and in 7 (G2(OH)) is of generation 2. (b) Schematic representation of the optical and
chemical processes for visible-light driven H2 evolution in a multicomponent system. The components are a sacrificial
electron donor (EDTA), metal complex sensitizer [Ru(bpy)3]2+ (bpy: 2,2’-bipyridine), an electron mediator
(methylviologen, MV2+: N,N'-dimethyl-4,4-bipyridinium) in acetic acid/sodium acetate buffer (pH = 5) and a hydrogen
generating catalyst (1, 5 and 7).
The inner coordination sphere of the designed complexes utilizes PtCl2(bpy) moiety as probe
catalyst. The outermost coordination sphere (peripheral) was decorated with carboxyl groups. In
the catalytic buffer solution (pH = 5), Figure 1b, the carboxyl groups were fully dissociated
(pKaGlu(COOH) = 3.5, 4.1).[21] The carboxylate groups facilitate catalyst solubility in water and
enhance proton-electron transfer (PET) by increasing the local concentration of protons and MV+• at
the peripheral.[27] The increasing number of carboxylates (7>5>1) was utilized to test the effect of
carboxylate group in catalytic performance, presumably by increasing the number of associated
MV+• species.[18] The role of peripheral group type in catalyst activity was further elaborated by
designing platinated peptide dendrimer conjugates having methoxy groups at the outermost
coordination sphere, namely (G1(OMe), 4) and generation 2 (G2(OMe), 6), Scheme 1.
The middle coordination sphere in the peptide conjugates consisted of amide groups, which act as
proton relay between the innermost and outermost coordination spheres.[14, 28] The methylene

12
alkyl groups of the L-glutmaic acid side chain modulated the dielectric around the Pt-center by
creating a hydrophobic core,[21] which with increasing dendrimer generation number (layers) the
methylene group number increases. The peptide layers of G1 and G2 are known to adopt open
conformation in water. Therefore, facilitate shuttling of electons, protons (H+) and releasing out
H2(g). To this end, we will address the following structural variations of peptide dendrimers on the
H2-evolving activity of the PtCl2(bpy) core: (i) Effect of amide functionality on the inner
coordination sphere (G0(OH) vs. G1(OH), G2(OH)). (ii) Number and type of peripheral groups of
the outermost coordination sphere, Gn(OMe) vs. Gn(OH) for n = 1, 2, and (iii) increasing peptide
layers around the core (encapsulation).
Synthesis: In the detailed syntheses, the peptide conjugates were prepared by applying a
complexation reaction between Pt-precursor with glutamic acid dendrimers having bpy at the core.
The 5,5'-dicarboxyl-2,2'-bipyridine (dcbpy) ligand is synthesized by oxidation of 5,5'-dimethyl-2,2'-
bipyridine using the reported literature procedure, which is depicted in scheme 1.[24] The
platination of dcbpy ligand using cis-PtCl2(DMSO)2 precursor, afforded Pt(dcbpy)Cl2 (G0(OH), 1)
complex as orange solid in good yield (44%), Scheme 1.
The synthesis of the G2 dendrons was demonstrated by the convergent growth approach using
conventional solution phase peptide coupling chemistry of N-α-Boc-L-Glu(OH)-OH and H2N-L-
Glu(OMe)-OMe of 1:2 stoichiometry in dry CH2Cl2, Scheme S1. In the following step, the G1 and
G2 dendrons were coupled with 5,5′-bis(chlorocarbonyl)-2,2'-bipyridine, in presence of Et3N in dry
CH2Cl2. The coupling reaction G1 (2) and G2 (3) dendrimers, as white solid products in (38%) and
(40%) yields, respectively, Scheme 1.

13
Scheme 1. Synthesis of compounds 1–7. (i) cis-PtCl2(DMSO)2, MeOH, 120 °C. (ii) SOCl2, THF, 40°C (iii) H2N-
Glu(OMe)-OMe·HCl/Et3N. (iv) Conjugate 4: K2PtCl4, EtOH/H2O (pH = 2.5), reflux. Conjugate 5: (1) NaOH in wet
methanol, 15 min, adjustment to pH = 2.5. (2) K2PtCl4, EtOH/H2O, (pH = 2.5), reflux. (v) Compound 3, Boc group
removal: TFA, neutralization of excess TFA by Et3N. (iv) Conjugate 6: cis-PtCl2(DMSO)2, MeOH, 120 °C. Conjugate
7: (1) NaOH in wet methanol, 15 min, adjustment to pH = 2.5. (2) cis-PtCl2(DMSO)2, MeOH, 120 °C.
The synthesis of Pt-conjugate G1(OMe) (4) was conveniently achieved by reacting K2PtCl4
with compound 2 under refluxing in ethanol/H2O mixture. Purification of 4 was readily
achieved by retro crystallization, affording 4 as green solid in good yield (55%). The Pt-
conjugate G1(OH) 5 was prepared by removing methyoxy group in 2 using base hydrolysis,

14
followed by a reaction of the resulting ligand to K2PtCl4 under refluxing in ethanol/H2O mixture
to afford conjugate 5 as green solid in acceptable yield.
When the synthetic strategy described above was employed to prepare Pt-conjugates G2(OMe)
(6) and G2(OH) (7), a black solid, attributable to colloidal platinum, was obtained.[29]
Therefore, Pt-conjugates 6 and 7 were prepared by complexation of 3 to cis-PtCl2(DMSO)2 in
methanol in an autoclave at 120°C. The final products were obtained as orange solids in
acceptable yields, (38%) and (27%), respectively.
The resulted products have shown different solublity behaviors. For example, complex 1 was
soluble in DMSO, slightly insoluble in water and completely insoluble in either methanol or
CH2Cl2. However, conjugates 4 and 6 were soluble in either methanol or CH2Cl2 but insoluble in
water. Conjugates 5 and 7 were soluble in water and methanol but insoluble in chlorinated solvents.
Characterization: The successful formation of the complexes 1, 4–7 were confirmed by mass
spectrometry, elemental analysis, UV-vis, infrared (IR), and 1H-, 13C-NMR spectroscopies. The full
1H-, 13C-NMR assignments were made on the basis of 2D TOCSY and HSQC. The relevant
spectroscopic data are summarized in Table 1.
Table 1. Selected spectroscopic characterization of Pt complexes 1 and 4–7.
UV-vis (λ, nm)[a]
1H NMR (ppm)[b]
IR (cm-1)[c]
NH
[d]
→bpy
Pt
Complex
H6, H6'
9.99
NHbpy
COOH COOCH3
COacid COester COamid
370
-
-
-
1700
-
-
1740
-
-
1
4
5
6
7
435
9.89
9.39
9.35
-
3.69, 3.60
3450, 3305
3450, 3290
3455, 3300
3480, 3260
1648
1650
1651
1650
390
9.90
12.62
-
1720
-
438
9.99
9.53, 9.80
-
3.70, 3.62
1745
390
9.87
9.80,9.49
-
-
1725
-
[a]Recorded in water. [b] 5 mM concentration in [D6] DMSO for complexes 1, 5 and 7. For complexes 4 and 6: 5 mM in CDCl3 at 24
°C. [c] IR recorded in KBr. [d] amide proximal to pyridine ring.
The observed mass spectrometry data well supported the validity of the formulations proposed for 1
and 4–7 Figs. S1–S3. The isotopic distribution patterns of the platinated products clearly revealed
the coordination of the platinum(II) to the bpy unit, Figures S1,S2. The elemental analyses results
further confirm the composition as well as purity of the synthesized complexes.
The UV-vis spectra for 1 and 4–7 displayed the characteristics absorption of the existed
→π*
chromophoric groups. The carbonyls n
transition of amides, acids and esters were at 255–290
nm range, the doublet peak of bpy (π→π* transition) was at 315–344 nm and the broad low intense
of Pt→bpy MLCT was at 360–400 nm, Fig. S4. These values were in good agreement to the
reported absorptions of related cis-PtCl2(bpy) complexes.[16, 30] The variation on the perceived

15
color of solid 4 and 5 (green) and of solid 1, 6 and 7 (orange), Figure S5, which has been preserved
in solution, is attributed to a possible aggregations of the monomers in 4 and 5 "polymeric
stacking". In contrast, the orange colored most likely indicates a "monomeric" form in complexes
1, 6 and 7.[31, 32]
Infrared spectroscopy (IR) has clearly shown the presence of the carboxyl and ester functional
groups in the Pt-complexes. The carboxyl group appeared in the region (1700-1720 cm-1) for the
complexes 1, 5, and 7. The ester group appeared at 1740 cm-1 for the complexes 4 and 6, Table 1
and Figs. S4–S6. Additionaly, the broad peak in the region 3600–2600 cm–1 were assigned to the
OH stretching modes of the carboxyl groups.[33] Complex 1 and Pt conjugates 4–7 exhibit a typical
amide A band at 3400 cm–1 and amide I at 1650 cm–1 as shown in Table 1.
1
The H NMR of 1 exhibits a downfield chemical shift of bpy proton peaks compared to the free
dcbpy ligand, Figure 2. Upon complexation, the singlet peak of H6,H6' (6,6'-bpy) protons, Scheme
1, was downfield shifted (δ9.29→δ9.99), Figure 2. This shift is related to the formation of
coordinate bond to the electron withdrawing Pt2+ center. The chemical shift of the H6, H6' singlet
peak has subsequently monitored the progress of the platination reaction in complexes 4–7.
Figure 2. Partial 1H NMR spectra of (a) dcbpy ligand, (b) (dcbpy)PtCl2 (1). (5 mM in [D6] DMSO).
The 1H NMR of 2 have proven the presence of the characteristic proton signals of the bpy ring and
the glutamic amino acid fragments, Figs. 3a and S8. The 1H NMR of 4, Fig. 3b, confirms successful
platination of 2 as evidenced by the downfield shift of H6,H6' singlet peak. The 1H NMR spectrum
of conjugate 5, Figure. 3c, have shown lack of the siganls of the methyoxy ester groups at δ3.69 and
δ3.60. In addition, a broad resonance peak appears at δ12.62, Fig. S7, and is assigned to the
carboxyl OH groups in 5.
1
The H NMR of conjugate 6 and 7 exhibits similar changes in chemical shift at the H6,H6' singlet
peak, Fig. S9. The 13C-NMR spectra of complexes 1 and 4–7 exhibit the peak for the carbonyl

16
carbon derived from the carboxyl group at ~ δ176–δ173, Fig. S10, while for the carbonyl carbon of
the ester group appears at ~ δ171, Fig. S11.
1
Figure 3. H NMR spectra of (a) compound 2 (5 mM in CDCl3). (b) Conjugate 4 (5 mM in [D6] DMSO) and (c)
conjugate 5 (5 mM in [D6] DMSO). * Residual CDCl3, ** residual CH2Cl2 in CDCl3, # residual [D6] DMSO, ## residual
water in [D6] DMSO.
DFT Calculations: Density functional theory (DFT) and Time-dependent density functional theory
(TD-DFT) calculations were carried out on the ground state of 1 and 5 in their monomeric form.
The calculation has utilized polarizable contium model (PCM) to account for solvent effects in
aqueous media. Optimized structure of 7 was not attainable, due to difficulties in obtaining
molecular structure that yielded satisfactorly converged ground state. The calculated UV-Vis
spectrum for 1 have shown intense band at 310 nm and moderatly intense band at 428 nm as a result
of several electronic transitions between molecular orbitals and virtuals (Figure 5a and Table S1).
On the other hand, complex 5 have shown three intense absorption bands at 384, 332 and 292 nm
(Figure 5b and Table S3). Inspite of the lack of agreement between the experimental and the
calcluated UV-Vis spectra (Fig. S4), the calculated spectra reproduce the main features of the
experimental spectra.
The long wavelength transition in 1, at 370 nm (experimentally) which was reproduced at 428 nm
theoretically, is due to transition from H-1 to LUMO (Table S2). The molecular orbital analysis
listed in Table S2, indicates that H-1 is 52% on the Pt core and 36% on Cl, whereas, the LUMO is
mainly located on the bpy lignad (96%). Thus, the long wavelength transition is a contribution of
metal to ligand charge transfer (MLCT) and halide (Cl) to ligand charge transfer (XLCT).[31] The

17
calculation shows that the strongest absorption line in this absorption band is mainly due the
transition from H-5 to LUMO, in which 99% of H-5 and 96% of LUMO are located at the bpy
ligand. The result indicates a ligand centered charge transitions (LC). Similar molecular orbital
analysis for 5 confirms that the long wavelength is MLCT and XLCT while shorter wavelength
bands are due to LC transitions.
Figure5: Calculated UV-is spectra for the ground state of (a) 1 (top), and (b) 5 (bottom).
The DFT study suggests that building amide functional groups in the bpy ligand alters its electronic
properties, this effect is clearly noticed from the shift in MLCT band from 428 nm in 1 to 384 nm in
5 and further confirmed from the calculated ∆E(LUMO-HOMO) = 3.32eV and 3.65eV for 1 and 5
respectively. It is expected that a similar change in the electronic properties would be occured to
bpy in 7 due to the similarity of the properties of the attached amide groups, this assumption is
supported by the identcal abosrption behavior of complex 5 and 7 in their UV-Vis spectra shown in
Fig. S4.

18
In conclusion, first, the experimental and quantum theortical calculations both indicates their is a
change in HOMO-LUMO gap upon amide bond formation for 5 and 7 and regardless of the
complex aggregation form. Secondly, The bathochrmic shift in MLCT transition, obtained from the
UV-Vis spectra shown in Fig. S4, for 5 and 7 compared to 1 suggests lowering of the energy gap.
Finally, the increasing dendrimer generation number (peptide branches) impacts the electronic
properties of the first coordination sphere, this is further evidenced from the emission spectra of the
complexes 1, 5 and 7, Fig. S16. Although the luminescence spectra displayed similar emission
features, there intensity are in the order 5 > 1 > 7.[34]
Conformational analysis: The asymmetric nature and conformational flexibility in glutamic amino
acid side chains should provide different magnetic environments for the H6,H6′ and NHbpy protons.
1
Interestingly, the H-NMR spectra for 4 and 5 revealed a sharp, similar chemical shifts for the
H6,H6′ and NHbpy protons as well as for the α-, β-, and γ-Glu protons, Figures 3b and 3c and Table
1. This observation indicates a C2 symmetry in 4 and 5, therefore, it is likely that the glutamic acid
side chains have identical orientation on both sides of bpy, Scheme 1.
For 6 and 7 conjugates, the 1H-NMR spectra have confirmed the presence of multiple peaks for the
H6,H6′ and NHbpy protons, (Figure S10 and Table 1), in addition, the Glu protons on G2 dendrons
exhibited broad chemical shifts, suggesting an asymmetric arrangement of G2 dendrons. This is
likely due to existence of several, non-identical orientations of the glutamic acid side chains in G2
dendrons, Scheme 1.
To provide insight into a potential aggregation in conjugates 4 and 5,[32, 34] variable temperature
(VT) UV-Vis study have been carried out. In case of aggregation, several possible intermolecular
interactions of the PtCl2(bpy) core were suggested, like π-π (aromatic of bpy) interactions or
ꢂ
ꢂ
ꢀꢁ − ꢀꢁ (Pt-Pt) interactions.[35] One would expect that with increasing temperature, the thermal
energy would drive weakening the intra-complex interactions present in 4 and 5. Subseqently this
affects the electronic properies of the stacked complexes, resulting in changes on their UV-vis
spectra, scheme 2.
Scheme 2: Depiction of possible stacking modes on conjugate 5 and their conversion to monomeric species upon
ꢂ
ꢂ
heating. The possible stacking interactions are: π-π (aromatic bpy), dꢃ − dꢃ (Pt-Pt), R = H2N-Glu(OH)-OH.

19
The impact of varying the temperature on the absorbance spectrum of 5 was studied and the results
were compared to the results obtained from 1 and 7. Analyses of the UV-vis spectra of 5 at 25, 40,
60 and 80°C revealed that the ligand based (LC) transition, which appears as doublet absorption
peaks (323 nm, 336 nm), exhibited a bathochromic shift (330 nm, 343 nm) upon raising the
temperature from 25°C to 40°C, Figure 6. Futhermore, upon increasing the temperatue to 60 and
80°C, the LC band has blue shifted to 320 nm 334 nm. It has been described that in systems
containing aromatic chromophores, the π→π* transitions exhibit a hypochromism and
bathochromic shifts in case of strong π*-orbital coupling interactions, while the hypsochromic shift
is an indicative of weak π*-orbital coupling interactions.[36] It seems that complex 5 starts to
→ "monomeric"
deaggregate from "polymeric" stacking
at 60 °C, evidenced by the blue shift in
π→π* transition peaks, this phase transition event of PtCl2(bpy) is associated with an increasing in
solution scattering. The LC band in 1 and 7 display a small blue shift at all temperature values,
which indicates the absence of stacking, Figures S12,S13.
Figure 6: Varible temperature (VT)-UV-vis of 5 (1mM)
In conclusion, the 1H-NMR and VT-UV-Vis studies confirm the stacking modes of monomers in 4
and 5 which presumably gives rise to the green color of the complexes in the solid state and
solution.[42] Unfortuntly, we have been unable to run VT-135Pt NMR to further confirm Pt-Pt
interactions in the aggregated mode of 4 and 5, therefore we will speculate its existance based on
literaure investigation on PtCl2(bpy) system and other related systems.[30, 35, 37]
Catalytic study: The catalytic activities of dendrimer 1 and 4–7 were evaluated employing these
complexes in the photochemical H2 evolution from water. This study was performed according to

20
our previously reported conditions.[24] However, applying the same catalytic process using
complexes 4 and 6 were unsuccessful due to their poor solubility in aqueous media. In general, for
the complexes 1, 5 and 7, an aqueous acetate buffer solution of each complex (1.0 M, pH = 5),
methylviologen, [Ru(bpy)3]2+, and sodium chloride, were used to study their catalytic activities,
(Figure1b). The induction period (~5–10 min) observed in each experiment is considered to
populate one-electron-reduced form of methylviologen (i.e., MV+·), (Figure S11). Furthermore, this
step ensures the absence of hydrogen evolution activity due to Pt nanoparticles.[24]
Table 2. Summary of the catalyst activity parameters.
Turnover ferquency (×1015 H2 molecule/sec)
Complex No. Initial rate (mL/min)
0.004
0.004
0.004
7
1
5
7
14.7
3.8
Figure 7. Photochemical H2 production of 1 (solid), 5 (dashed), 7 (dotted).
The number of turnovers frequencies (TOFs) of catalysts 1, 5 and 7 are estimated on the basis of the
total amount of H2 evolved after 5 hr and the amount of each catalyst (1 µmol), (Figure 7 and Table
2). The catalytic activity for H2 formation is found to decrease in the order of 5 > 1 > 7.
The catalytic behaviour in PtCl2(bpy) systems is likely to be accelerated by formation of dinuclear
ꢂ
ꢂ
complex intermediate, presumbly using ꢀꢁ (ꢄꢅ) − ꢀꢁ (ꢄꢅ) interactions. It has been shown that the
overall catalytic activity of Pt-molecular catalyst for H2-evolution from water is accelerated by
adding extra Pt-based complexes as co-catalyst,[38] implying the formation of heteroleptic
intermediate utilizing Pt...Pt bond.
The observation was explained by The properties of 5,
including distinct green color, rigid conformation of the glutamic residues and its dissociation in
responce to heating, supports the hypothesis of aggregate formation. The higher H2 activity in 5 in

21
comparison to 1 and 7 further indicates the existance of Pt-Pt interactions though it is not proven in
this study. This interaction seems to be in favor for the case of G1 dendrons, while the G2 dendron
branches prevent the formation of aggregates in 7, most likely due to steric hindrance.
The number of carboxylate groups at the dendrimer peripherals in 7 has no effect on inceseaing the
H2 evolution activity. In the contrary, the G2 dendron branches seems to isolate the PtCl2(bpy) core
from the surrounding aqueous medium (encapsulation effect). Similar encapsulation effects have
been reported in Ferrocene-glutamic acid dendrimers.[21]
Conclusions
Four new Pt-glutamic acid dendrimer conjugates have been synthesized 4-7. The natural L-glutamic
amino acid layers were built into the bpy ligand framework (G0(OH), 1). The G0(OH) is the
unmodified parent complex PtCl2(5,5'-dicarboxylic acid-2,2'-bipyridine). The N-terminus of the
dendrimer is attached to the G0(OH) utilizing amide bond formation at the 5,5'-position, whereas
the C-terminus are terminated with methoxy (OMe) or carboxy (OH) groups. These dendrimers are
of generation 1, (G1(OMe), 4 and G1(OH), 5, and generation 2 (G2(OMe), 6 and G2(OH), 7. The
structure and composition of these conjugates have been determined by various spectroscopic
techniques.
The amide bond formation has altered the electronic properties of the bpy ligand indicated by the
DFT calculations. The type of functional group (ester vs. acid) at the dendrimers peripheral
influences the solubility behavior of the synthesized conjugates in water. The conformational study
has indicated a aggregation order of generation 1 conjugates (4,5) evidenced by their apparent color,
rigidity and the alteration in their electronic properties in response to temperature.
The H2-evolution photocatalytic activitiy of water soluble conjugates 1, 5 and 7 are well correlated
to the ability of the conjugate to form a polynuclear structure. Apparently, the increasing number of
carboxylic acid groups at the peripheral has no influence on increasing H2-activities, instead the
barrier for electron and proton transfer has increased with bulky G2 dendrimers (encapsulation
effect). The work presented in this article leaves the question of possible existence of Pt-Pt
interactions unanswered in Pt(II)-L-glutamic acid conjugates. Currently, we are developing systems
of Pt(II)-L-aspartic acid conjugates. Arguably, these conjugates will have less steric hindrance and
would allow facile aggregate formation.
Acknowledgments
A. Lataifeh wishes to thank University of Western Ontario/Chemistry Department for ASPIRE
award and Dr. T. Ashboul/ Friedrich Schiller-University of Jena for runing the elemental analysis.
A. Lataifeh is grateful to financial support from Tafila Technical University(TTU)/Jordan (grant
number: 150/2012). This work was funded by Natural Sciences and Engineering Research Council

22
of Canada (NSERC) and the University of Western Ontario (UWO). This work was partly
supported by the International Institute for Carbon Neutral Energy Research (WPI-I2CNER),
sponsored by the World Premier International Research Center Initiative (WPI), MEXT, Japan.
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Highlights:
•
•
•
•
•
Four new platinum-L-glutamic acid dendrimer conjugates have been synthesized
The dendrimer contains dichlorobipyridineplatinum(II) complex at the dendrimer core
The conjugates characterization have been performed by spectroscopic techniques
The dendrimers pose a substantial electronic and steric impact on the platinum core
The dendrimer size effects the reduction rate of protons to molecular hydrogen

25
A series of platinum-glutamic amino acid conjugates have been synthesized. The identities of the bioconjugates have
1
been confirmed by H-, 13C NMR, UV-vis and IR spectroscopy as well as mass (MS) spectrometry. The platinum
bioconjugates have shown different reactivity towards the visible-light induced water splitting to generate hydrogen gas.
The catalyst structure-activity relationship is disuccsed