Titanium complexes supported by imidazo[1,5-a]pyridine-containing pyrrolyl ligand as catalysts for hydroamination and polymerization reactions, and as an antitumor reagent

Article abstract of DOI:10.1039/c4ra14692a

A new imidazo[1,5-a]pyridine-containing pyrrolyl ligand HL (HL = 3-(1H-pyrrol-2-yl)imidazo[1,5-a]pyridine) was synthesized and employed in the organometallic chemistry of titanium. The syntheses, structures, catalytic properties and antitumor activity of three titanium complexes supported by HL are reported. Reactions of Ti(NMe₂)₄ and Ti(NEt₂)₄ with 2 equivalents of HL, led to the production of titanium bisamido complexes TiL₂(NMe₂)₂ (1) and TiL₂(NEt₂)₂ (2), respectively. Treatment of Ti(OⁱPr)₄ with 2 equivalents of HL resulted in the formation of TiL₂(OⁱPr)₂ (3). All complexes were characterized by elemental analyses and NMR studies. The solid-state structures of 2 and 3 were further established by single X-ray crystallography. The titanium bisamido complexes 1 and 2 are shown to be good pre-catalysts for the hydroamination of alkynes. Complex 1 was found to be an active catalyst for the ring-opening polymerization of ε-caprolactone. The cytotoxicity activities of 3 towards the tumor cells HCT-116, PC3 and MCF-7 were measured. Complex 3 exhibited good antitumor properties.

Full text of DOI:10.1039/c4ra14692a

View Article Online
View Journal
RSC Advances
This article can be cited before page numbers have been issued, to do this please use: J. Liu, Y. Cao, L.
Li, H. Pei, Y. Chen, J. Hu, Y. Qin, Y. Li, W. Li and W. Liu, RSC Adv., 2014, DOI: 10.1039/C4RA14692A.
This is an Accepted Manuscript, which has been through the
Royal Society of Chemistry peer review process and has been
accepted for publication.
Accepted Manuscripts are published online shortly after
acceptance, before technical editing, formatting and proof reading.
Using this free service, authors can make their results available
to the community, in citable form, before we publish the edited
article. This Accepted Manuscript will be replaced by the edited,
formatted and paginated article as soon as this is available.
You can find more information about Accepted Manuscripts in the
Information for Authors.
Please note that technical editing may introduce minor changes
to the text and/or graphics, which may alter content. The journal’s
standard Terms & Conditions and the Ethical guidelines still
apply. In no event shall the Royal Society of Chemistry be held
responsible for any errors or omissions in this Accepted Manuscript
or any consequences arising from the use of any information it
contains.
www.rsc.org/advances

Page 1 of 9
RSC Advances
View Article Online
DOI: 10.1039/C4RA14692A
Titanium complexes supported by imidazo[1,5-a]pyridine-
containing pyrrolyl ligand as catalysts for hydroamination
and polymerization reactions, and as antitumor reagent
Jinna Liu, Yuhua Cao, Lei Li, Hao Pei, Yanmei Chen, Jinfa Hu, Yaru Qin, Yahong Li,* Wu Li
and Wei Liu*
The syntheses, structures, catalytic properties and antitumor activity of three titanium complexes
supported by an imidazo[1,5-a]pyridine-containing pyrrolyl ligand are reported.

RSC Advances
Page 2 of 9
View Article Online
DOI: 10.1039/C4RA14692A
RSC Advances
RSCPublishing
ARTICLE
Titanium complexes supported by imidazo[1,5ꢀ
a]pyridineꢀcontaining pyrrolyl ligand as catalysts for
hydroamination and polymerization reactions, and as
antitumor reagent
Cite this: DOI: 10.1039/x0xx00000x
Received 00th January 2012,
Accepted 00th January 2012
Jinna Liu,a Yuhua Cao,b Lei Li,a Hao Pei,a Yanmei Chen,a,c Jinfa Hu,a Yaru Qin,a
Yahong Li,*a Wu Lic and Wei Liu*a
DOI: 10.1039/x0xx00000x
www.rsc.org/
A new imidazo[1,5ꢀa]pyridineꢀcontaining pyrrolyl ligand HL (HL = 3ꢀ(1
Hꢀpyrrolꢀ2ꢀ
yl)imidazo[1,5ꢀ ]pyridine) has been synthesized and employed to the organometallic
a
chemistry of titanium. The syntheses, structures, catalytic properties and antitumor activity
of three titanium complexes supported by HL are reported. Reactions of Ti(NMe2)4 and
Ti(NEt2)4, respectively, with 2 equivalents of HL, lead to the production of titanium
bisamido complexes TiL2(NMe2)2 (
equivalents of HL results in the formation of TiL2(OiPr)2 (
characterized by elemental analyses and NMR studies. The solidꢀstate structures of
have been further established by single Xꢀray crystallography. The titanium bisamido
complexes and are shown to be good preꢀcatalysts for the hydroamination of alkynes.
Complex was found to be active catalyst for the ringꢀopening polymerization of εꢀ
caprolactone. The cytotoxicity activities of towards the tumor cells HCTꢀ116, PC3 and
MCFꢀ7 were measured. Complex exhibited good antitumor properties.
1
) and TiL2(NEt2)2 (
2
). Treatment of Ti(OiPr)4 with
). All complexes have been
and
2
3
2
3
1
2
1
3
3
ligands, e.g., Cpꢀbased molecules,7 pyrrolyl ligands,8 amidate
compounds,9 imidazoleꢀcontaining ligands10 and phenolate,11 etc.,
are reported. However, employment of a multidentate ligand in
which a pyrrolyl moiety and a Nꢀcontaining heterocycle were
incorporated in one molecule entity, has rarely been explored.
Aiming at exploring the influences of the structure of the ligands on
the regioselectivity of the hydroamination products and continuing
our ongoing efforts on studying the hydroamination of alkynes
catalyzed by titanium compounds supported by pyrrolyl ligands,8aꢀb
we expand our efforts to synthesize titanium preꢀcatalysts
coordinated by 3ꢀ(1Hꢀpyrrolꢀ2ꢀyl)imidazo[1,5ꢀa]pyridine (HL,
Scheme 1), which contains both a pyrrolyl ring and an imidazo[1,5ꢀ
a]pyridine moiety. The reactions of HL with Ti(NMe2)4, Ti(NEt2)4,
and Ti(OiPr)4, respectively, gave complexes TiL2(NMe2)2 (1),
TiL2(NEt2)2 (2) and TiL2(OiPr)2 (3). Herein we report the syntheses
and characterizations of these complexes. The catalytic activities of
1 and 2 towards the intermolecular hydroamination of alkynes, the
ringꢀopening polymerization of εꢀcaprolactone initiated by 1, and the
cytotoxicity activities of 3 towards the tumor cells HCTꢀ116, PC3
and MCFꢀ7 were also investigated.
Introduction
The organometallic chemistry of titanium has received growing
attention from many groups around the world.1 The efforts of these
groups are driven by a number of impetuses, but the three most
important factors are the development of precatalysts for alkyne and
alkene hydroamination reactions,2 the employment of titanium
complexes as the initiators for the polymerization of olefin3 and
cyclic ester,4 and the investigation of cytotoxicity of titanium
compounds towards cancer cells.5 Hydroamination is the addition of
NꢀH bond across an unsaturated CꢀC bond. Since hydroamination of
alkyne or alkene provides an important avenue for the efficient
synthesis of imines, enamines and nitrogenꢀcontaining heterocycles
with a 100% atomꢀeconomical fashion, hydroamination reaction has
been the subject of everꢀincreasing scrutiny over the past two
decades.2 Numerous catalysts based on the elements stretched across
the periodic table have been found to be able to catalyze this
transformation.6 Among which the titanium complexes have been
proved particularly useful.2aꢀc The advantages of titanium catalysts
over late transition metals are improved cost effectiveness and low
toxicity. The titanium compounds are also preferred over rareꢀearth
catalysts owing to their enhanced robustness and broad functional Results and discussion
group scope.
Synthesis of the HL ligand
The recent advances of titanium catalyzed hydroamination reveal
that the regiochemical outcome of the reaction could be dramatically
controlled by utilizing different ligands. Thus, a plethora of ancillary
The ligand HL was prepared by the reaction of 1Hꢀpyrroleꢀ2ꢀ
carbonyl chloride and 2ꢀpyridylmethanamine in the presence of T3P
(50 wt% in DMF). The ligand HL was obtained in good yield and
This journal is © The Royal Society of Chemistry 2013
J. Name., 2013, 00, 1-3 |
1

Page 3 of 9
ARTICLE
RSC Advances
VJieowuArrtnicalelONnlainme e
DOI: 10.1039/C4RA14692A
was characterized by 1H and 13C NMR spectra.
N
N
NH
HL
Scheme 1 Structure of the ligand.
Fig. 1 ORTEP structural drawing of 2.
Syntheses of the titanium complexes
Treatment of HL with THF solution of Ti(NMe2)4 and
Ti(NEt2)4, respectively, led to the formations of TiL2(NMe2)2
(
1
) and TiL2(NEt2)2 (
2
) (Scheme 2). The reaction of Ti(OiPr)4
with 2 equiv. of HL afforded TiL2(OiPr)2
(3) (Scheme 2).
Complexes 1ꢀ3 were readily obtained in good yields. They were
1
also characterized by H and 13C NMR spectra and elemental
analyses.
Crystals suitable for Xꢀray diffraction of
2 and 3 were grown
from toluene solutions which were left standing at room
temperature in a vibrationꢀfree environment for a week.
Fig. 2 Partially labeled structure of one of molecules of 2.
Scheme 2 Syntheses of TiL2(NMe2) (
TiL2(OiPr)2 ).
1), TiL2(NEt2) (2) and
(
3
Structure descriptions of 2 and 3
The molecular structures of 2 and 3 in the solid state have been
confirmed by Xꢀray analysis and are shown in Figs. 1, 2 and 3,
respectively. The crystallographic data and experimental details for
structural analyses are summarized in Table 1. Selected bond
distances and angles are listed in Table 2.
The single crystal analysis revealed that 2 crystallizes in
monoclinic crystal system of the P21/c space group and displays
several interesting features. The overall structure of 2 includes two
molecules (Fig. 1), and the two individual molecules are not
completely symmetrical. The central Ti(IV) atom is sixꢀcoordinated
by four nitrogen atoms from two bidentate Lꢀ ligands and two
amides in cis arrangement, displaying a distorted octahedral
coordination environment. The bond lengths between titanium atom
and donor imidazopyridine nitrogen atoms (Ti1ꢀN1 = 2.236(3) Å,
and Ti1ꢀN4 = 2.277(3) Å ) are apparently longer than those of the Ti
–N(pyrrolyl) distances (Ti1ꢀN2 = 2.148(3) Å, and Ti1ꢀN4 =
2.123(3) Å). One donor imidazopyridine nitrogen atom of the ligand
and one amide atom are in trans arrangement, with bond angles of
87.69(10)º (N2ꢀTi1ꢀN3) and 97.53(11)º (N5–Ti1–N2), summing
to185.22º（Fig. 2) .
Fig. 3 ORTEP structural drawing of 3.
2
| J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 2012

RSC Advances
Page 4 of 9
View Article Online
Journal Name
ARTICLE
DOI: 10.1039/C4RA14692A
Table 1 Crystal data and structure refinements for 2 and 3
Table 2 Selected bond lengths (Å) and angles (°) for 2 and 3
Ti(1)ꢀN(1)
Ti(1)ꢀN(3)
Ti(1)ꢀN(5)
2.236(3)
2.277(2)
1.912(3)
76.45(9)
74.90(10)
88.51(10)
84.61(9)
162.79(10)
97.53(11)
96.26(11)
102.32(12)
Ti(1)ꢀN(2)
Ti(1)ꢀN(4)
Ti(1)ꢀN(6)
N(2)ꢀTi(1)ꢀN(3)
N(5)ꢀTi(1)ꢀN(3)
N(2)ꢀTi(1)ꢀN(1)
N(5)ꢀTi(1)ꢀN(1)
N(4)ꢀTi(1)ꢀN(2)
N(6)ꢀTi(1)ꢀN(2)
N(6)ꢀTi(1)ꢀN(4)
2.148(3)
2.123(3)
1.910(3)
87.69(10)
167.17(11)
73.82(10)
93.69(11)
155.02(10)
97.57(11)
99.70(11)
Complex
2
3
Empirical formula
Formula weight
Temperature
Wavelength
C30H36N8Ti
556.54
C28H30N6O2Ti
530.45
N(1)ꢀTi(1)ꢀN(3)
N(4)ꢀTi(1)ꢀN(3)
N(6)ꢀTi(1)ꢀN(3)
N(4)ꢀTi(1)ꢀN(1)
N(6)ꢀTi(1)ꢀN(1)
N(5)ꢀTi(1)ꢀN(2)
N(5)ꢀTi(1)ꢀN(4)
N(6)ꢀTi(1)ꢀN(5)
3
Ti(1)ꢀO(1)
Ti(1)ꢀO(1A)
Ti(1)ꢀN(1)
O(1)ꢀTi(1)ꢀN(1)
O(1)ꢀTi(1)ꢀN(1A)
O(1)ꢀTi(1)ꢀN(2)
O(1)ꢀTi(1)ꢀN(2A)
O(1A)ꢀTi(1)ꢀO(1)
O(1A)ꢀTi(1)ꢀN(1)
O(1A)ꢀTi(1)ꢀN(1A)
296(2) K
293(2) K
0.71073 Å
Monoclinic
P21/c
0.71073 Å
Monoclinic
C 2/c
Crystal system
Space group
1.7799(13)
1.7798(13)
2.2209(16)
90.02(6)
167.20(6)
103.11(6)
95.96(6)
100.41(9)
167.20(6)
90.02(6)
Ti(1)ꢀN(1A)
Ti(1)ꢀN(2)
Ti(1)ꢀN(2A)
O(1A)ꢀTi(1)ꢀN(2A)
N(1A)ꢀTi(1)ꢀN(1)
N(2)ꢀTi(1)ꢀN(1)
N(2)ꢀTi(1)ꢀN(1A)
N(2A)ꢀTi(1)ꢀN(1)
N(2A)ꢀTi(1)ꢀN(1A)
N(2A)ꢀTi(1)ꢀN(2)
2.2209(15)
2.1003(16)
2.1004(16)
103.11(6)
80.70(8)
74.28(6)
82.96(6)
82.96(6)
74.28(6)
a = 23.010(9) Å
b =13.712(5) Å
c = 21.228(9) Å
α = 90°
a = 8.7336(17) Å
b =16.212(6) Å
c = 18.952(4) Å
α = 90°
Unit cell dimensions
150.07(9)
β =115.456(7)°
γ = 90°
β =92.30(3) °
γ = 90°
O(1A)ꢀTi(1)ꢀN(2)
95.96(6)
The single crystal Xꢀray diffraction determination indicates that
the octahedral Ti(IV) ion of 3 is surrounded by four nitrogen atoms
(N1, N2, N1A, and N2A) from two Lꢀ ligands and two oxygen atoms
(O1 and O1A) from isopropoxide groups. The N1, O1, N1A, and
O1A atoms are equatorial coplanar, with the bond angles of
90.06(6)º, 100.41(9)º, 90.02(6)º and 80.70(8)º, respectively,
summing to 361.19º, with the deviation being 1.19º compared with
360º. The bond lengths between titanium atom and donor
imidazopyridine nitrogen atoms (Ti1ꢀN1 = 2.2209(16) Å, and Ti1ꢀ
N1A = 2.2209(15) Å) are apparently longer than those of the Ti–
N(pyrrolyl) distances (Ti1ꢀN2 = 2.1003(16) Å, and Ti1ꢀN2A =
2.1004(16) Å).
Volume
6048(4) Å3
8
2681.2(13) Å3
4
Z
ρ(mg•mꢀ3)
F(000)
1.222
1.314
2352
1112
Crystal size(mm3)
θ range/°
0.60 x 0.40 x 0.40
1.78° to 26.22
ꢀ28 ≤ h ≤ 23
ꢀ25 ≤ l ≤ 26
ꢀ16 ≤ k ≤ 17
35810 / 12166
12094 / 0 / 711
0.950
0.60 x 0.40 x 0.40
3.31° to 27.49°
ꢀ9 ≤ h ≤ 11
ꢀ20 ≤ k ≤ 20
ꢀ24 ≤ l ≤ 24
12023 / 3070
3048 / 0 / 170
1.076
Hydroamination of alkynes catalyzed by 1 and 2
To evaluate the catalytic activities of 1 and 2, we investigated the
reactions of aniline with a selection of alkynes (diphenylacetylene,
3ꢀhexyne, 3ꢀoctyne, phenylacetylene, 1ꢀhexyne, and 1ꢀoctyne)
catalyzed by 10 mol% of 1 or 2. The results are shown in Table 3.
As we can see in Table 3, both 1 and 2 could catalyze the
hydroamination of 1ꢀhexyne and 1ꢀoctyne (entries 4, 5, 9 and 11).
The Markovnikov product is favored product of hydroamination. No
hydroamination product was determined for symmetric alkynes.
To further probe the scope of the catalysis, a larger selection of
amines was screened in reactions with 1ꢀoctyne. The results are
shown in Table 4. Again, the Markovnikov product is highly
favored. In the presence of 1 or 2, most arylamines hydroaminated 1ꢀ
octyne in >60% yield and with high regioselectivities. This is in
contrast to utilizing Me2TiCp2 as the precatalyst,12 which yielded
antiꢀMarkovnikov products. In addition, most of substituted anilines
gave better yields. However, when 2ꢀchloroaniline was employed as
the amine source, low yields with high regioselectivities were
observed (Table 4, entries 5 and 6). 2ꢀMethoxyꢀphenylamine can be
used to hydroaminate 1ꢀoctyne with lower regioselectivities (Table
4, entries 17 and 18). In generral, the yields of hydroamination of
alkynes catalyzed by 2 are higher than that of 1. This is probably due
to the slightly larger steric impediment of the diethyl amide group.
The yields of the hydroamination reactions by 1 or 2 are higher than
that of Ti(imidazolꢀ2ꢀyl)(NMe2)3.10
Limiting indices
Reflections collected/ unique
Data / restraints / parameters
GOF
R1 = 0.0507
wR2 = 0.1111
R1 = 0.1290
wR2 = 0.1438
R1 = 0.0456
wR2 = 0.1289
R1 = 0.0578
wR2 = 0.1365
﹥
R1,wR2[I 2σ(I)]
R1,wR2(all data)
Largest diff. peak and
hole(e•Å3)
0.276 and ꢀ0.249
0.369 and ꢀ0.271
This journal is © The Royal Society of Chemistry 2012
J. Name., 2012, 00, 1-3 |
3

Page 5 of 9
ARTICLE
RSC Advances
VJieowuArrtnicalelONnlainme e
DOI: 10.1039/C4RA14692A
Table 3 Hydroamination of alkynes with 4ꢀbromoaniline catalyzed
by complexes 1 or 2
19
20
21
94:6
91:9
99:1
78
83
84
1
2
1
NH2
22
99:1
95
2
M/ant
iꢀMb
Yield
(%)a
a Isolated yields after reduction by LiAlH4. b By GCꢀMS analysis.
Entry Catalyst
Alkyne
Product
1
2
3
1
Ringꢀopening polymerization of εꢀcaprolactone initiated by
complex 1
Metalꢀcatalyzed ringꢀopening polymerization (ROP) of lactones is
one of the most promising processes for the preparation of
environmentally friendly and biomedical polyesters, and it provides
an alternative in the synthesis of wellꢀcharacterized biodegradable
polymers. While rare earth metal complexes were well known to
efficiently catalyze the polymerization of lactones because of the
highly electropositive nature of the lanthanides,13 the titanium(IV)
complexes have also been found to initiate the polymerization of εꢀ
caprolactone over the past few years.14 The titanium compounds
chelated by alkoxide or aryloxide ligands have long been recognized
to have significant applications in polymerization catalysis, 15 but the
potential of titanium complexes supported by imidazopyridineꢀ
containing pyrrolyl ligands, has never been explored. Thus, we
investigated the catalytic behavior of complexes 1, 2 and 3 towards
ringꢀopening polymerization of εꢀcaprolactone.
4
5
88:12
98:2
38
73
6
7
8
2
9
92:8
97:3
47
91
The initial studies were performed using TiL2(OiPr)2 (3) as the
initiator. It was found that 3 showed low activity for the
polymerization. The polymerization reaction proceeded very slowly
and low yields of polymers were generated after 24 h at 60°C (Table
S4, Supporting Information). Next, the polymerization recation was
conducted by employing 1 as the initiator, and utilizing dimethyl
ether (DME), tetrahydrofuran (THF), and toluene, respectively, as
the solvents at 60°C and 80°C. To our delight, complex 1 can
effectively initiate εꢀcaprolactone polymerization, and the obtained
polymers have high molecular weights and relatively narrow
molecular weight distributions (PDIs). The polymerization results
are summarized in Table 5. The solvents have the obvious effect on
the yields of the polymers. When the polymerization was conducted
in THF, poor or moderate yields were afforded (68% and 60% in
THF). However, no observable polymerization initiated by complex
2 occurred at 80°C after 24 h.
10
a Isolated yields after reduction by LiAlH4. b By GCꢀMS analysis.
Table 4 Hydroamination of 1ꢀoctyne with amines catalyzed by 1 and
2
Entry
Amine
Product
Cat.
M/antiꢀM
Yield (%)
1
2
3
4
5
6
7
8
9
92:8
97:8
97:3
95:5
94:6
91:9
96:4
94:4
99:1
73
91
70
77
22
21
65
79
93
1
2
1
2
1
2
1
2
1
H
N
Cytotoxicity
Cl
Recently, titanium (IV) complexes have been studied as antitumor
compounds with the expectation for substituting for platinum
compounds.17 The ‘salan’ isopropoxide titanium(IV) complexes,
which are based on tetradentate diaminobis(phenolato) ligands were
demonstrated high antitumor activity;18 whereas the cytotoxicity of
the ‘pyrrolyl’ isopropoxide titanium(IV) complexes was rarely
studied.19 In order to investigate the influences of the ligand
structures on the properties of the Ti(IV) complexes, we studied the
anticancer features of complex 3.
NH2
Cl
10
87:13
85
2
Cl
The cytotoxic activity of 3 was studied on HCTꢀ116, PC3 and
MCFꢀ7 cells, employing the methylthiazolylꢀdiphenylꢀtetrazolium
bromide (MTT) assay. Relative IC50 and maximal inhibition values
are listed in Table 6. Cytotoxicity plots are given in Fig. 4.
It is evident that 3 exhibits variable cytotoxicity. Compared with
cisplatin,20 complex 3 shows an obvious cytotoxic effect towards
HCTꢀ116, PC3 and MCFꢀ7 cells, with the IC50 values of 21.87,
31.37 and 14.17 ꢁM, respectively. These IC50 data are close to or
better than cisplatin (3.79, 33.3, and 46.9 ꢁM towards HCTꢀ116,
PC3 and MCFꢀ7 cells, respectively).
11
12
13
14
15
16
92:8
100:0
94:6
52
79
72
59
68
86
1
2
1
2
1
2
96:4
92:8
89:11
NH2
O
17
18
75:25
62:38
62
77
1
2
4
| J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 2012

RSC Advances
Page 6 of 9
View Article Online
Journal Name
ARTICLE
DOI: 10.1039/C4RA14692A
Table 5 Polymerization of εꢀcaprolactone initiated by 1
Entry
Initiator
solvent
DME
DME
THF
THF
Tol
[M]/[I]
200
t/h
5
Yield/%a
T/°C
80
Mn(calc) b(104)
1.87
Mnc(104)
2.67
Mn(obsd)d (104)
PDI
1.39
1.50
1.49
1.39
1.22
1.47
Efficiency/%
1
2
3
4
5
6
1
1
1
1
1
1
82
79
68
60
89
86
1.49
1.30
1.39
1.09
1.85
1.26
70.0
77.2
53.4
70.4
61.5
87.0
200
10
12
17
3
60
1.80
2.33
200
80
1.55
2.48
200
60
1.36
1.94
200
80
2.03
3.30
Tol
200
4
60
1.96
2.25
aYield: weight of polymer obtained/weight of monomer used. bMn(calc) = Mmono*[M]/[I] *Conv. cMeasured by GPC relative to polystyrene
standards. dMeasured by GPC relative to standards with MarkꢀHouwink corrections16 for Mn (obsd) = 0.56 Mn (GPC) for εꢀcaprolactone.
Table 6 Relative IC50 and maximal inhibition values for 3
Experimental section
IC50
maximal inhibitiona (%)
General considerations
Compound
HCTꢀ116
21.87
PC3
MCFꢀ7
14.17
HCTꢀ116
PC3
81
MCFꢀ7
83
All manipulations of airꢀsensitive compounds were carried out
in an MBraun glovebox in a purified nitrogen atmosphere.
Anhydrous THF, DME and toluene were freshly distilled from
Ti (OiPr)2L2 (3)
31.37
89
a The concentrations of complex 3 are all 250 ꢁM.
1
purple sodium benzophenone ketyl for at least 4 days. H and
13C spectra were recorded on Innovaꢀ400 spectrometers at
ambient temperature using TMS as an internal standard, and
chemical shifts of carbon, hydrogen and nitrogen atoms were
performed with a Carlo
–Erba EA1110 CHNOS microanalyzer.
Xꢀray crystallography
Crystals grown from concentrated solutions at room
temperature were quickly selected and mounted on a glass fiber
in wax. The data collections were carried out with a Mercury
CCD detector equipped with graphiteꢀmonochromated MoꢀKα
radiation by using the φ/ω scan technique at room temperature.
The structures were solved by direct methods with SHELXSꢀ
97.21 The hydrogen atoms were assigned with common
isotropic displacement factors and included in the final
refinement by use of geometrical restraints. A fullꢀmatrix leastꢀ
squares refinement on F2 was carried out using SHELXLꢀ97.
General procedure for hydroamination reactions
To a 30 mL pressure tube was added the preꢀcatalyst (0.1 mmol),
amine (1.5 mmol), alkyne (1 mmol) and toluene (5 mL) in a drybox.
The pressure tube was sealed with a Teflon screw cap, taken out of
the drybox and heated at 120°C for 24 h. Then at 0°C the reaction
Fig. 4 Cell survivals in response to complex 3 towards cell HCTꢀ116, solution was carefully added to a suspension of LiAlH4 in toluene
and the mixture was refluxed for 12 h at 60°C. After cooling the
solution to 0°C, the excess LiAlH4 was hydrolyzed with sodium
sulphate decahydrate. The mixture was filtered to remove sodium
sulphate decahydrate.The solvent was concentrated under vacuum.
Column chromatography of the residue on silica gel afforded the
pure amine derivatives.
PCꢀ3, MCFꢀ7.
Conclusions
In summary, three complexes TiL2(NMe2)2 (1), TiL2(NEt2)2 (2),
and TiL2(OiPr)2 (
3) were synthesized and characterized. The
catalytic behaviors of these complexes towards the
hydroamination of alkynes, ringꢀopening polymerization of εꢀ
caprolactone and their cytotoxicity were investigated.
Typical polymerization procedure
A THF solution of complex 1 (0.0250 g, 0.05 mmol) and εꢀ
caprolactone (1.14 g, 10 mmol) was added to a 30 mL pressure tube
equipped with a magnetic stirring bar in a glovebox. Afterwards, the
pressure tube was taken out from the glovebox. The reaction mixture
was heated to 80°C for 12 h and then terminated by addition of a
mixture of conc. HCl/EtOH (1:5 V/V) (2 mL). Petroleum ether (20
mL) was added to give yellow solids. The solids were dissolved in
THF (20 mL), column chromatography on Al2O3 to give a white
solid. Yield: 0.78 g (68 %).
Complexes
alkynes, and showed higher catalytic activity and gave highly
Markovnikov selective hydroamination of 1ꢀoctyne. Complex
1 and 2 were able to catalyze the hydroamination of
1
also exhibited good catalytic activity for ringꢀopening
polymerization of εꢀcaprolactone. High cytotoxicities were
obtained for 3, indicating that pyrrolyl–titanium(IV) complexes
may serve as a new family of antitumor agents towards HCTꢀ
116, PC3 and MCFꢀ7 cells.
This journal is © The Royal Society of Chemistry 2012
J. Name., 2012, 00, 1-3 |
5

Page 7 of 9
ARTICLE
RSC Advances
VJieowuArrtnicalelONnlainme e
DOI: 10.1039/C4RA14692A
H 6.57; N 19.71%.
General considerations for cytotoxicity
Cytotoxicity was measured on colorectal cancer cell HCTꢀ116,
adenocarcinoma MCFꢀ7 and PCꢀ3 using the methylthiazolyldiphenyl Ti(OiPr)2L2 (3). To a solution of Ti(OiPr)4 (0.1421 g, 0.5 mmol) in
tetrazolium bromide (MTT) assay. HCT 116 cells were cultured at tetrahydrofuran (2 mL), HL (0.1830 g, 1.0 mmol) in tetrahydrofuran
37°C in a 5% CO2 atmosphere incubator in modified McCoy's 5A was added at room temperature. After stirring at room temperature
medium (sigma) complemented with 10% fetal bovine serum (FBS, for at least 24 h, THF was evaporated completely under reduced
Hyclone) containing 1% penicillin and 1% streptomycin (Sigma). pressure to give an orange solid. The product was obtained as light
MCFꢀ7 was maintained in RPMI 1640 medium with 10% FBS and orange block crystals after crystallized from toluene. Yield: 80%
1
PC3 in Fꢀ12K medium with 10% FBS. For cytotoxicity assay, HCT (0.4135 g). H NMR (400 MHz, CDCl3) δ 7.89 (d, 2H, C7H5N2 ),
116, MCFꢀ7 and PCꢀ3 cells were seeded into 96ꢀwell plates at 7.51 (d, 2H, C7H5N2), 7.15 – 7.00 (m, 2H, C7H5N2), 6.59 (d, 2H,
densities of 5000 cells per well and maintained for 24 h. Next, the pyrroleꢀH), 6.52 – 6.38 (m, 6H, C7H5N2 + pyrroleꢀH), 6.20 (s, 2H,
cells were incubated with the reagents tested at different pyrroleꢀH), 4.79 – 4.58 (m, 2H, CH), 1.17 (d, 6H, CH3), 1.00 (d, 3H,
concentrations for another 72 h in modified McCoy's 5A medium CH3). 13C NMR (101 MHz, CDCl3) δ 138.63, 132.05, 128.74,
containing 10% FCS. After that, MTT (5 mg/mL in 20 ꢁL) was 128.21, 121.92, 119.15, 117.76, 115.90, 113.49, 108.42, 103.41,
added and the cells were incubated for additional 4 h. The 79.19, 25.55. Anal. Calc. for C28H30N6O2Ti: C 63.40; H 6.70; N
supernatant was removed, and the precipitates were dissolved in 150 15.84%. Found: C 63.73; H 5.60; N 16.23%.
mL of DMSO. The absorbance at 490 nm was measured. Relative
IC50 values with standard error of means were determined by a
nonlinear regression of a variable slope model.
Acknowledgements
We thank Professor Zhijun Zhang of Suzhou Institute of Nanotech
and Nanoꢀbionics for assistance with cytotoxicity measurement. The
authors appreciate the financial supports of Natural Science
Foundation of China (21272167 and 21201127), A Project Funded
by the Priority Academic Program Development of Jiangsu Higher
Education Institutions, and KLSLRC (KLSLRCꢀKFꢀ13ꢀHXꢀ1).
Synthesis of the ligand and complexes 1ꢀ3
3ꢀ(1Hꢀpyrrolꢀ2ꢀyl)imidazo [1,5ꢀa]pyridine (HL). To a stirred
solution of 1Hꢀpyrroleꢀ2ꢀcarbonyl chloride (10 mmol) in CH2Cl2
was added pyridine (2 mL) followed by substituted 2ꢀ
pyridylmethanamine (10 mmol) at room temperature. The reaction
mixture was stirred for 1 h and added 30 mL water. The reaction was
neutralized by NaHCO3 and extracted with ethylacetate; then the
organic layer was dried and concentrated to give the amide (Nꢀ
(pyridinꢀ2ꢀylmethyl)ꢀ1Hꢀpyrroleꢀ2ꢀcarboxamide). To the amide
added 9 mL of T3P (50 wt% in DMF) and refluxed for 3 h at 125°C.
Notes and references
a
College of Chemistry, Chemical Engineering and Materials Science,
Soochow
University,
Suzhou
215006,
China.
E-mail:
liyahong@suda.edu.cn; weiliu@suda.edu.cn.
This was poured into cold water and neutralized with ammonia b Suzhou Institute of Nano-tech and Nano-bionics, Chinese Academy of
solution. The water layer was extracted three times with ethylacetate.
The combined organic phases were dried over anhydrous Na2SO4
and evaporated under vacuum. The residue, thus obtained was
purified by column chromatography using ethylacetate and hexane
Sciences, Suzhou 215125, China.
c
CAS Key Laboratory of Salt Lake Resources and Chemistry, Qinghai
Institute of Salt Lakes, Chinese Academy of Sciences, Xining 810008,
China
1
as solvent system to get the product. H NMR (400 MHz, CDCl3) δ
† Electronic Supplementary Information (ESI) available:Crystallography,
1H and 13C NMR data. CCDC reference numbers 1030010 and 990411
12.14 (s, 1H), 8.39 – 8.28 (m, 1H), 7.51 (s, 1H), 7.45 (d, 1H), 7.02
(d, 1H), 6.76 – 6.58 (m, 3H), 6.41 (dd, 1H); 13C NMR (101 MHz,
CDCl3) δ 133.32, 130.71, 122.01, 119.86, 119.21, 118.72, 118.33,
113.31, 109.16, 106.07. Anal. Calc. for HL: C 72.11; H 4.95; N
22.94%. Found: C 71.79; H 5.06; N 22.61%.
for complex
2 and 3, respectively. For ESI and crystallographic data in
CIF or other electronic see DOI: 10.1039/b000000x/
1
For selected examples, see: (
Chem. Res., 2005, 38, 839ꢀ849; (
Kaltsoyannis and P. Mountford, Chem. Sci., 2012,
H. Li, Y. H. Shi and A. L. Odom, J. Am. Chem. Soc., 2004, 126
1794ꢀ1803; ( ) I. Prochnow, P. Zark, T. Müller and S. Doye, Angew.
Chem., Int. Ed., 2011, 50, 1 – 6; (
2002, 35, 575ꢀ582; ( ) S. W. Hu, T. Shima and Z. M. Hou, Nature
2014, 512, 413ꢀ415; (
Luo and Z. M. Hou, Science, 2013, 340, 1549ꢀ1552; (
Z. W. Xie, J. Am. Chem. Soc., 2010, 132, 11473ꢀ11480; (
Cavaliere, M. G. Crestani, B. Pinter, M. Pink, C. Chen, M. Baik and
D. J. Mindiola, J. Am. Chem. Soc., 2011, 133, 10700–10703; ( ) R.
a
) N. Hazari and P. Mountford, Acc
) A. D. Schwarz, A. J. Nielson, N.
, 819–824; ( ) Y.
TiL2(NMe2)2 (1). To a solution of Ti(NMe2)4 (0.112 g, 0.5 mmol) in
THF (2 mL) was added dropwise HL (0.1830 g, 1 mmol) in THF (5
mL). After stirring at room temperature for 24 h, the volatiles were
removed under reduced pressure to give a red solid. Yield: 0.47 g
(93%). 1H NMR (400 MHz, CDCl3) δ 7.93 (d, 2H, C7H5N2), 7.54 (s,
2H, C7H5N2), 7.06 (d, 2H, C7H5N2 ), 6.62 (d, 2H, pyrroleꢀH), 6.53 –
6.39 (m, 6H, C7H5N2 + pyrroleꢀH), 6.28 (s, 2H, pyrroleꢀH), 3.35 (s,
12H, CH3 ). 13C NMR (100 MHz, CDCl3) δ 138.41, 130.93, 129.01,
128.70, 122.06, 119.09, 117.65, 115.87, 113.31, 108.90, 103.68,
68.17, 47.37. Anal. Calc. for C26H28N8Ti: C 62.40; H 5.64; N
22.39%. Found: C 62.32; H 5.82; N 22.43%.
b
3
c
,
d
e
) L. H. Gade, Acc. Chem. Res.
,
,
f
g
) T. Shima, S. W. Hu, G. Luo, X. H. Kang, Y.
) H. Shen and
) V. N.
h
i
TiL2(NEt2)2 (2). The synthesis of complex 2 was carried out in the
same way as that described for complex 1, but Ti(NEt2)4 (0.186 g,
0.5 mmol) was used instead of Ti(NMe2)4. The volatiles were
removed under reduced pressure to give a redꢀbrown solid. Yield:
j
Thompson, C. Chen, M. Pink, G. Wu and D. J. Mindiola, J. Am.
Chem. Soc., 2014, 136, 8197–8200.
1
0.50 g (89%). Red crystals were obtained in toluene. H NMR (400
2
For selected reviews and recent papers, see: (
Hultzsch, M. Yus, F. Foubelo and M. Tada, Chem. Rev., 2008, 108
3795; ( ) A. L. Odom, Dalton Trans., 2005, 225ꢀ233; ( ) G. F. Zi, J.
Organomet. Chem., 2011, 696, 68ꢀ75; ( ) R. Severin, S. Doye, Chem.
Soc. Rev., 2007, 36, 1407ꢀ1420; ( ) H. Shigehisa, N. Koseki, N.
Shimizu, M. Fujisawa, M. Niitsu and K. Hiroya, J. Am. Chem. Soc.
a) T. E. Müller, K. C.
MHz, CDCl3) δ 7.94 (d, 2H, C7H5N2), 7.61 (s, 2H, C7H5N2), 7.06 (d,
2H, C7H5N2), 6.62 (d, 2H, pyrroleꢀH), 6.47 (dd, 8H, C7H5N2 +
pyrroleꢀH), 4.22 – 3.74 (m, 8H, CH2), 0.62 (t, 12H, CH3). 13C NMR
(101 MHz, CDCl3) δ 137.92, 131.65, 128.84, 128.25, 121.99,
118.92, 117.44, 115.76, 113.05, 108.71, 103.24, 45.21, 12.82. Anal.
Calc. for C30H36N8Ti: C 64.74; H 6.52; N 20.13%. Found: C 64.83;
,
b
c
d
e
,
6
| J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 2012

RSC Advances
Page 8 of 9
View Article Online
Journal Name
ARTICLE
DOI: 10.1039/C4RA14692A
2014, 136, 13534ꢀ13537; (
f
) A. J. Musacchio, L. Q. Nguyen, G. H.
and M. Terada, Org. Lett., 2014, 16, 4198ꢀ4200; (
Takahashi and Y. Ogiwara, Eur. J. Org. Chem., 2014, 2014, 5078ꢀ
5082; ( ) C. B. Huehls, A. J. Lin and J. Yang, Org. Lett.
2014, 16, 3620ꢀ3623; ( ) M. J. Gainer, N. R. Bennett, Y. Takahashi
and R. E. Looper, Angew. Chem., Int. Ed., 2011, 50, 684ꢀ687; ( ) S.
Germain, E. Schulz and J. Hannedouche,
ChemCatChem, 2014, , 2065ꢀ2073; ( ) G. Zi, Dalton Trans., 2009,
9101ꢀ9109; ( ) J. C. Bernhammer, N. X. Chong, R. Jothibasu, B. B.
Zhou and H. V. Huynh, Organometallics, 2014, 33, 3607ꢀ3617. (
A. L. Reznichenko, H. N. Nguyen and K. C. Hultzsch, Angew.
Chem., Int. Ed., 2010, 49, 8984ꢀ8987; ( ) M. Zille, A. Stolle, A. Wild
and U. S. Schubert, RSC Advances, 2014, 4, 13126ꢀ13133; ( ) S. B.
Amin and T. J. Marks, J. Am. Chem. Soc., 2007, 129, 10102ꢀ10103;
) E. Kumaran, W. Y. Fan and W. K. Leong, Org. Lett.
2014, 16, 1342ꢀ1345; (w) T. Andrea and M. S. Eisen, Chem. Soc.
Rev., 2008, 37, 550ꢀ567; ( ) B. D. Stubbert and T. J. Marks, J. Am.
Chem. Soc., 2007, 129, 4253ꢀ4271.
) R. Kubiak, I. Prochnow and S. Doye, Angew. Chem., Int. Ed.
2010, 49, 2626ꢀ2629; ( ) E. Haak, I. Bytschkov and S. Doye, Angew.
Chem., Int. Ed., 1999, 38, 3389ꢀ3391.
) F. Y. Zhou, M. S. Lin, L. Li, X. Q. Zhang, Z. Chen, Y. H. Li, Y.
Zhao, J. Wu, G. M. Qian and B. Hu and W. Li, Organometallics
2011, 30, 1283ꢀ1286; ( ) Z. Chen, L. Li, Y. M. Chen, B. Hu, J. Wu,
X. F. Wang and T. Lei, Y. H. Li, J. Chem. Res., 2012, 36, 249ꢀ253;
) D. L. Swartz, R. J. Staples and A. L. Odom, Dalton Trans.
2011, 40, 7762ꢀ7768; S. Majumder and A. L. Odom,
Organometallics, 2008, 27, 1174ꢀ1177; ( ) D. L. Swartz and A. L.
m) N. Sakai, N.
Beard and R. R. Knowles, J. Am. Chem. Soc., 2014, 136, 12217ꢀ
12220; ( ) A. R. Ickes, S. C. Ensign, A. K. Gupta and K. L. Hull, J.
Am. Chem. Soc., 2014, 136, 11256ꢀ11259. ( ) A. Zhdanko and M. E.
Maier, Angew. Chem. Int. Ed., 2014, 53, 7760ꢀ7764; ( ) T. M.
Nguyen, N. Manohar and D. A. Nicewicz, Angew. Chem. Int. Ed.
2014, 53, 6198ꢀ6201; ( ) M. J. Goldfogel, C. C. Roberts and S. J.
Meek, J. Am. Chem. Soc., 2014, 136, 6227ꢀ6230.
) F. Gornshtein, M. Kapon, M. Botoshansky and M. S. Eisen,
Organometallics, 2007, 26 497ꢀ507; ( ) I. Saeed, S. Katao and K.
Nomura, Organometallics, 2009, 28, 111ꢀ122; ( ) K. H. Tam, M. C.
W. Chan, H. Kaneyoshi, H. Makio and N. Zhu, Organometallics
2009, 28, 5877ꢀ5882; ( ) W. H. Sun, S. Liu, W. Zhang, D. Wang and
T. Liang, Organometallics, 2010 , 24, 732ꢀ741; ( ) M. Delferro and
T. J. Marks, Chem. Rev., 2011, 111, 2450ꢀ2485; ( ) L. Wang, Q. Wu,
H. Xu and Y. Mu, Dalton Trans., 2012, 41, 7350ꢀ7357; ( ) X. C. Shi
and G. X. Jin, Organometallics, 2012, 31, 7198ꢀ7205; ( ) S. Liu, A.
Motta, M. Delferro and T. J. Marks, J. Am. Chem. Soc., 2013, 135
8830ꢀ8833; ( ) S. Liu, A. Motta, A. R. Mouat, M. Delferro and T. J.
Marks, J. Am. Chem. Soc., 2014, 136, 10460ꢀ10469; ( ) J. G. M.
g
n
,
h
o
i
p
,
j
6
q
r
3
(a
s)
,
b
c
t
,
u
d
e
(
v
,
f
g
x
h
,
7
8
(a
,
i
b
j
Morton, H. AlꢀShammari, Y. Sun, J. Zhu and D. W. Stephan, Dalton
Trans., 2014, 43, 13219ꢀ13231.
(a
,
4
(
a
) R. R. Gowda, D. Chakraborty and V. Ramkumar, Inorg. Chem.
Commun., 2011, 14, 1777–1782; ( ) E. L. Whitelaw, M. D. Jones, M.
F. Mahon and G. KociokꢀKohn, Dalton Trans., 2009, 9020–9025; (
D. Deivasagayam and F. Peruch, Polymer, 2011, 52, 4686ꢀ4693; (
b
b
c
)
)
(c
,
d
(d)
C. Y. Li, C. J. Yu and B. T. Ko, Organometallics, 2013, 32
172−180; ( ) R. L. Webster, RSC Adv., 2014, , 5254–5260; ( ) C. Y.
Tsai, H. C. Du, J. C. Chang, B. H. Huang, B. T. Ko and C. C. Lin,
RSC Adv., 2014, , 14527–14537.
) R. Hernandez, J. Mendez, J. Lamboy, M. Torres, F. R. Roman
and E. Melendez, Toxicol. in Vitro, 2010, 24, 178–183; ( ) S.
,
e
e
4
f
Odom, Organometallics, 2007, 26, 6684ꢀ6684.
9
J. C. H. Yim, J. A. Bexrud, R. O. Ayinla, D. C. Leitch and L. L.
4
Schafer, J. Org. Chem., 2014, 79, 2015ꢀ2028; (b) P. R. Payne, R. K.
5
6
(a
Thomson, D. M. Medeiros, G. Wan and L. L. Schafer, Dalton
Trans., 2013, 42, 15670ꢀ15677.
b
GómezꢀRuiz, B. Gallego, Ž. Žižak, E. HeyꢀHawkins, Z. D. Juranić 10 Y. Zhao, M. S. Lin, Z. Chen, H. Pei, Y. H. Li, Y. M. Chen, X. F.
and G. N. Kaluđerović, Polyhedron, 2010, 29, 354–360; (
c
) L. M.
Wang, L. Li, Y. Y. Cao, Y. Zhang and W. Li, RSC Adv., 2012, 2,
Gao, J. Matta, A. L. Rheingold and E. Meléndez, J. Organomet.
Chem., 2009, 694, 4134–4139.
144ꢀ150.
11 (
a
)
I. A. Tonks, J. C. Meier and J. E. Bercaw,
) B. Lian, T. P. Spaniol, P.
(a
) S. D. Lee, J. C. Timmerman and R. A. Widenhoefer, Adv. Synth.
Catal., 2014, 356, 3187ꢀ3192; ( ) A. G. M. Barrett, C. Brinkmann,
M. R. Crimmin, M. S. Hill, P. Hunt and P. A. Procopiou, J. Am.
Chem. Soc., 2009, 131, 12906ꢀ12907; ( ) M. A. Savolainen, X. P. 12 (
Han and J. Wu, Org. Lett., 2014, 16, 4349ꢀ4351; ( ) M. R. Crimmin, 11485ꢀ11589; (
M. Arrowsmith, A. G. M. Barrett, I. J. Casely, M. S. Hill and P. A. Int. Ed.,1999, 38, 3389ꢀ3391.
Procopiou, J. Am. Chem. Soc., 2009, 131, 9670ꢀ9685; ( ) Z. Chai, D. 13 ( ) Y. M. Yao, X. P. Xu, B. Liu, Y. Zhang, Q. Shen and W. T. Wong,
Z. Hua, K. Li, S. L. Zhou, J. Chu and G. S. Yang, J. Organomet. Inorg. Chem., 2005, 44, 5133ꢀ5140; ( ) Y. M. Yao, M. T. Ma, X. P.
Chem., 2014, 768, 136ꢀ139; ( ) A. Mukherjee, S. Nembenna, T. K. Xu, B. Liu, Y. Zhang, Q. Shen and W. T. Wong, Organometallics
Sen, S. P. Sarish, P. K. Ghorai, H. Ott, D. Stalke and H. W. Roesky, 2005, 24, 4014ꢀ4020; ( ) T. J. Woodman, M. Schormann, D. L.
Angew. Chem., Int. Ed., 2011, 50, 3968ꢀ3972; ( ) J. F. Dunne, D. B. Hughes and M. Bochmann, Organometallics, 2004, 23, 2972ꢀ2979.
Fulton, A. Ellern and A. D. Sadow, J. Am. Chem. Soc., 2010, 132 14 ( ) H. Wang, H. Chan, J. Okuda and Z. Xie, Organometallics, 2005,
17680ꢀ17683; (g) M. R. Maurya, A. Arya, U. Kumar, A. Kumar, F. 24, 3118ꢀ3124; ( ) X. Wang, A. Thevenon, J. L. Brosmer, I. Yu, S. I.
Avecilla and J. C. Pessoa, Dalton Trans., 2009, 9555ꢀ9566; ( ) K. D.
Hesp, S. Tobisch and M. Stradiotto, J. Am. Chem. Soc., 2010, 132
413; ( ) K. D. Hesp and M. Stradiotto, J. Am. Chem. Soc., 2010, 132
18026ꢀ18029; (
Organometallics, 2013, 32, 3451ꢀ3457; (b
b
HorrilloꢀMartinez and K. C. Hultzsch, J. Okuda, Eur. J. Inorg.
Chem., 2009, 429ꢀ434.
c
a
) P. L. McGrane and T. Livinghouse, J. Am. Chem. Soc.,1993, 115
,
d
b
) E. Haak, I. Bytschkov and S. Doye, Angew. Chem.,
d
a
b
e
,
c
f
,
a
b
h
Khan, P. Mehrkhodavandi and P. L. Diaconescu, J. Am. Chem. Soc.
,
,
2014, 136, 11264–11267.
i
,
15 (
a
b
) C. Li, C. Yu and B. T. Ko, Organometallics, 2013, 32, 172ꢀ180;
)M. G. Davidson, M. D. Jones, M. D. Lunn and M. F. Mahon,
j
) S. R. Mothe, M. L. Novianti, B. J. Ayers and P. W.
(
H. Chan, Org. Lett., 2014, 16, 4110ꢀ4113; (
S. T. Madrahimov and J. F. Hartwig, J. Am. Chem. Soc., 2011, 133
2772ꢀ2782; ( ) I. Nakamura, T. Onuma, R. Kanazawa, Y. Nishigai
k
) Z. Liu, H. Yamamichi,
Inorg. Chem., 2006, 45, 2282ꢀ2287.
16 A. Kowalski, A. Duda and S. Penczek, Macromolecules, 1998, 31
2114ꢀ2122.
,
,
l
This journal is © The Royal Society of Chemistry 2012
J. Name., 2012, 00, 1-3 |
7

Page 9 of 9
ARTICLE
RSC Advances
VJieowuArrtnicalelONnlainme e
DOI: 10.1039/C4RA14692A
17 K. M. Buettner and A. M. Valentine, Chem. Rev., 2012, 112, 1863ꢀ
1881.
18 (
Tshuva, Chem. Med. Chem., 2012,
Manna, D. Peri and E. Y. Tshuva, Dalton Trans., 2011, 40, 9802ꢀ
9809; ( ) M. Shavit, D. Peri, C. M. Manna, J. S. Alexander and E. Y.
Tshuva, J. Am. Chem. Soc., 2007, 129, 12098ꢀ12099; ( ) D. Peri, S.
Meker, C. M. Manna and E. Y. Tshuva, Inorg. Chem., 2011, 50
1030ꢀ1038; ( ) D. Peri, S. Meker, M. Shavit and E. Y. Tshuva, Chem.
-Eur. J., 2009, 15, 2403ꢀ2415; ( ) E. Y. Tshuva and D. Peri, Coord.
Chem. Rev., 2009, 253, 2098ꢀ2115; ( ) C. M. Manna, G. Armony and
E. Y. Tshuva, Inorg. Chem., 2011, 50, 10284ꢀ10291; ( ) C. M.
Manna, G. Armony and E. Y. Tshuva, Chem.-Eur. J., 2011,17
14094ꢀ14103; ( ) S. Meker, K. MargulisꢀGoshen, E. Weiss, S.
a
) C. M. Manna, O. Braitbard, E. Weiss, J. Hochman and E. Y.
7
, 703ꢀ708; ( ) S. Meker, C. M.
b
c
d
,
e
f
g
h
,
i
Magdassi and E. Y. Tshuva, Angew. Chem., 2012, 124, 10667 –
10669.
19 M. Lin, Y. Cao, H. Pei, Y. Chen, J. Wu, Y. Li and W. Liu, RSC Adv.
2014, , 9255ꢀ9260.
,
4
20 G. Kelter, N. J. Sweeney, K. Strohfeldt, H. Fiebig and M. Tacke,
Anticancer Drugs, 2005, 16, 1091ꢀ1098.
21 G. M. Sheldrick, SHELXSꢀ97, Program for solution of
crystalstructures, University of Göttingen, Germany, 1997.
8
| J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 2012