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HIGHLIGHT

Crystal Shape Engineering of Anatase TiO2 and Its

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Cite this: DOI: 10.1039/x0xx00000x

Biomedical Applications

CrystEngComm Accepted Manuscript

Received 00th January 2012,
Accepted 00th January 2012
DOI: 10.1039/x0xx00000x
www.rsc.org/
Shuang Yang,†a Nian Huang,†b Yong Mei Jin, b Hui Qing Zhang, b Yong Hua Su*b
and Hua Gui Yang*a
As an important metal oxide, titanium dioxide (TiO 2) materials, particularly in anatase
phase, have been extensively investigated and utilized in many technological applications
due to its excellent physicochemical properties. The surface properties, as well as the
performance in various applications are largely determined by external surfaces exposed, and
thus crystal shape engineering is paramount for this type of materials. This review
summarizes the recent progress in designing and fabricating anatase TiO 2 crystals from the
perspectives of thermodynamics and kinetics controlled routes. Furthermore, the bio-
inspired technique is also highlighted which would open a new field for the growth of single
crystals with unique morphology. The strength of crystal shape engineering of anatase TiO2
in biomedical applications is also identified that opportunities for continued research and
specific areas where significant advancements are needed.

1. Introduction
Titanium dioxide has been widely applied as pigments,
sunscreens, paints, ointments and many other commercial
products due to its high optical refractive ability, chemically
stability and low toxicity. During recent decades, it has also
been one of the most important and fundamental materials,
especially in the field of energy and environmental
applications. This was initialled in 1972, that Fujishima and
Honda published the finding of photocatalytic splitting of water
by a TiO2 electrode under ultraviolet (UV) light, which offers a
promising way for clean, low-cost and environmentally friendly
production of hydrogen fuel from solar energy.1 Since then,
TiO2 has been extensively studied and remained as one of the
most important candidates used as photovoltaic devices,
photocatalysis, photodegradation, energy storage and
electrochromic devices.2-11
In addition to these success, approaches of TiO2 in
biomedical applications are exciting and, have made it a
promising material for health care, especially cancer treatment.
12-17
For instance, based on its excellent photocatalytic activity,
photoexcited TiO2 demonstrates the capability to kill cancer
cells effectively, and it can also be applied as a nucleic acid
endonuclease, which is of vital importance to genetic
engineering.
Undoubtedly, the unique physicochemical properties are not
only impacted by the intrinsic characteristics, but also by
crystal shape, size, doping and polymorph. Because of the
significant impact of crystal shape distributions, general
methodologies for the prediction, measurement, and techniques, modeling, and simulation have led to an improved
improvement of crystal shape are highly desired for product understanding of TiO2 crystal growth. The growth of crystals
and process design. These topics have been studied for a long generally have two controlling factors: thermodynamics and
period, recent breakthroughs in theoretical and experimental kinetics, which jointly determine the geometries of the

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products. In this highlight article, we will focus on the recent
shape engineering advances of anatase TiO2 crystals by
thermodynamic and kinetics controlled techniques (Fig. 1).
Concerning the promising prospect of the bio-inspired route, it
will also be highlighted which usually yields crystals with
unique morphologies. The physicochemical applications of the
tailored TiO2 crystals, such as photovoltaic devices,
photocatalysis and photodegradation, have been reviewed
recently and will not be included in this article. On the other
hand, the surface effect of anatase TiO2 crystals on biomedical
applications has not been reviewed and will be summarized in
this highlight article. Although the biomedical progress of
tailored anatase TiO2 crystals are relatively limited, the reported
results are attractive and promising which will provide some
invigorating perspectives to future directions.
2. Crystal shape engineering
2.1 Equilibrium morphology of anatase TiO2
TiO2 generally has three major crystalline polymorphs: anatase
(tetragonal, a = b = 3.782 Å, c = 9.502 Å), rutile (tetragonal, a =
b = 4.584 Å, c = 2.953 Å) and brookite (rhombohedral, a =
5.436 Å, b = 9.166 Å, c = 5.135 Å), which are commonly
recognized to occur naturally. Rutile is the only stable phase in
the bulk form, while bulk brookite and bulk anatase are
metastable and transform irreversibly to rutile upon heating.
However, anatase is the most widely investigated one because
of its high performance in various applications including
photocatalytic degradation of organic dye molecules,
photocatalytic water splitting and dye-sensitized solar cells. All
these phases can be viewed as constructed by Ti-O octahedra
connected by a variable number of shared corners, edges,
and/or faces. For anatase TiO2, each octahedron is in contact
with eight neighbours (four sharing an edge and four sharing a
corner) as shown in Fig. 2a.
Thermodynamic equilibrium criteria of solid/liquid
interface was firstly developed by Gibbs that its surface Gibbs
free energy is minimized by assuming a shape of low surface
energy.18 Then Wulff found that the length of a vector drawn
normal to a crystal face would be proportional to its surface energy
as shown in the following equation,19
γ ⁄  

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Here, the vector  is the length of the i th face drawn
perpendicularly from the center of the crystal to the face and γ is
the corresponding surface free energy. Then the geometric shapes
of well-developed crystals can be determined by this principle
which is known as the Wulff construction. The surface energy
of the crystal facets is close related to the surface atomic
structures. The high surface energy surface normally exhibits a
7
high density of atomic steps, ledges and kinks. For anatase
TiO2, the {001} surface enables a high density of surface
undercoordinated Ti atoms with higher reactivity in contrast
with {101} facets. Theoretical calculation results have also
demonstrated that the average surface energy of {001} is much
larger than {101} facets (with the average surface energies of
CrystEngComm Accepted Manuscript
0.44 and 0.90 J m-2 for {101} and {001}) which are the
common surfaces for naturally occurred crystals.20, 21 Therefore,
the equilibrium shape built through Wulff construction is a
slightly truncated tetragonal bipyramid enclosed by eight
thermodynamically stable {101} facets (typically more than 94%
percent) and two {001} facets as shown in Fig. 2b. This has
also been illustrated by a host of experimental results.22 Dinh et
al. has reported the solvothermal synthesis of controlled anatase
TiO2 nanobipyramids by using water vapor and oleic
acid/oleylamine as hydrolysis agent and capping agent,
respectively.23 Such technique enables the rhombic, truncated
rhombic, truncated and elongated rhombic shaped anatase TiO2
crystals. The incorporation of sodium fluoride can generate
anatase nanobipyramids with controlled {101} and {001}
facets.24 We have employed a high purity synthetic system with
only Ti, H, and O elements, which also gave rise to bipyramid
shaped anatase crystals.25 By a hydrothermal treatment of
titanate nanowires, anatase TiO2 crystals bounded with even
100% {101} facets can be yielded, which is as the most
thermodynamic stable facet.22 In these processes, the active
{001} facets were diminished by the rapid growth or orient
attachment along {001} directions under reaction conditions.
More specifically, the {101} surface, which is the most
prevalent face for anatase crystals, is corrugated with
alternating rows of 5-coordinate Ti atoms and bridging oxygen
(Fig. 3a), which are at the edges of the corrugations.
Interestingly, the {001} surface exhibits exclusively five-fold-
coordinated (5c) Ti atoms together with two raised 2c and two
lowered 3c oxygens bonding in the [100] and [010] directions,
respectively (Fig. 3b). The surface corrugation would increases
slightly, from 0.82 to 0.95 Å upon the relaxation process, and
thus, the {001}-(1×1) surface is relative unstable and can be
reconstructed into the (1×4) configuration.26 Also, many studies
have proven that the minor {001} facets exhibit higher
reactivity in contrast with {101} facets because of a high
density of surface undercoordinated Ti atoms.21, 27, 28 This
emphasizes the significance of crystal shape engineering of
anatase TiO2, especially the synthesis of uniform and highly
pure crystals with controllable crystallographic {001} facets.
2.2 Thermodynamic controlled synthesis
2.2.1 Anatase TiO2 with {001} facets
Thermodynamic controlled synthesis typically involves capping
agents, which adhere to the surfaces in the growth medium of
growing crystals, change the surface energy of different crystal
facets, and thus the merit of this technique has prompted
agents to control the thermodynamic equilibrium crystal
shapes.29, 30 Generally, crystals are synthesized in solution by
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shape dependent thermodynamic model31 suggest that F-

terminated surfaces have the highest degree of truncation and
thus TiO2 dominated by {001} facets should be accessible in
the F-rich experimental condition.
In 2008, we have succeed in the synthesis of anatase single
crystals with a large percentage of {001} facets by a
hydrothermal route using titanium tetrafluoride (TiF4) and
hydrofluoric acid (HF) as Ti precursor and morphology
controlling agent, respectively. The resultant anatase TiO2
crystals appeared as highly truncated bipyramids with two
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square {001} surfaces and eight isosceles trapezoidal {101}

surfaces. Subsequently, a host of works have been devoted to
the synthesis of anatase crystals with high-reactive facets. The

CrystEngComm Accepted Manuscript

synergistic functions of 2-propanol and HF was incorporated on
the growth of anatase TiO2 single crystals. It was found that 2-
propanol as both reaction medium and protecting agent, can
heterolytically dissociate to form an alkoxy group ((CH3)2CHO-
) bound to coordinatively unsaturated Ti4+ cations on the {001}
and {101} surfaces under acidic conditions. That is, the {001}
surfaces with high density of 5-fold Ti should be more readily
to be absorbed and stabilized by 2-propanol. Similar alcohols
such as ethanol, tert-butanol and benzyl alcohol as the
synergistic agents were also illustrated with combined effect
with HF.34 As a result, the preferred growth of anatase TiO2
was stimulated to achieve high {001} facet ratios (64% for 2-
propanol) which all displayed superior photoreactivity
compared to P25. These interesting results again emphasize the
significance of the realization of high reactive {001} surfaces,
not only for the fundamental study of surface chemistry but also
for the various practical applications.
To grow anatase crystals with higher percentage of {001}
facets, Xie et al. has reported a simple hydrothermal method by
using tetrabutyl titanate and hydrofluoric acid solution as the
titanium source and solvent, respectively. Excitingly, the
percentage of highly reactive {001} facets in such TiO2 crystals
is up to 89%. More importantly, the size of such crystals can be
successfully extended into the nanoscale (side length~40 nm,
thickness~6 nm) with considerably enhanced photolytic
ability.35 Then the influence of hydrofluoric acid was
reacting molecular metal precursors with appropriate capping
agents in the presence of capping agents to stabilize the high
energy surface and protect them from aggregation. By using
different capping agents, certain facets can be stabilized with
lower surface energy and finally exposed. Currently, the choice
of capping agents is by two methods: the most commonly used
is depended on empirical experience and the other strategy is
starting at the prediction by theoretical calculation. For anatase
TiO2, {100} facets are the most stable surface under
oxygenated conditions, while {101} facets are the most stable
under clean and hydrogenated conditions.31. Based on
theoretical calculation, anatase surfaces terminated with H and
O adsorbate atoms exhibit high surface energies (γ) because of
the high bonding energies (D0) of H–H (436.0 kJ mol-1) and O–
O (498.4 kJ mol-1).32 We therefore carried out a systematic
study of 12 non-metallic atoms (X) as adsorbates (X = H, B, C,
N, O, F, Si, P, S, Cl, Br, or I) based on first principle
calculations.33 The absorption behaviour and the calculated
surface energy values for different adsorbates are calculated as
shown in Fig. 3. It was that F adsorbate atoms yield the lowest
surface energies which reversely indicate that large anatase
TiO2 single crystals are likely to be formed upon the fluorine
rich condition. More interestingly, for F-terminated anatase
surfaces, {001} surfaces are preferential and more stable,
compared to {101} surfaces. Further prediction based on the

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systemically studied. And it was also found that the thickness
of the as-synthesized TiO2 nanosheets is dependent on the
concentration of HF.36 By a judicious tuning of its
concentration, {001} facets dominated anatase TiO2 nanosheets
with the thickness of 1.6 nm were prepared, that is, only two
layers of crystal units along the [001] crystallographic direction
can be integrated into the entire matrix. As a complementary,
the crystal growth behaviour of the {001} facets dominated
anatase crystals were also probed under the hydrothermal
condition.37 Within only deionized water, anatase TiO2
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nanosheets can grow into larger single crystals with a truncated
bipyramidal shape through an oriented attachment process
along the [001] crystallographic direction, driven by the
minimization of surface energy. These nanosheets are gradually
combined as one single crystals upon the coarsening behaviour,
in a process which the {001} surface are reversely reduced. On
the other hand, nanosized anatase crystals with {001} surface
can also be produced by a heterogeneous nucleation technique
upon a tight control of the number of nucleation sites on a silica
substrate.38 The substrate and anatase crystals were
spontaneously separated under hydrothermal condition owning
to the occurrence of the reaction product, HF. Overall, the size
can be finely tuned form the micron scale into several tens of
nanometres.
Although {001} facet dominated anatase TiO2 crystals have
been successfully extended into the nanoscale, to approach
100% of such facets are desired as a final goal in this field. This
can be realized by loading anatase TiO2 crystals onto substrates
with tailored {001} facets.39 The polycrystalline anatase films
are continuous, coat the whole substrate and exhibit a high
degree of preferred orientation with the c-axis normal to the
substrate surface. However, the high ratio of {001} facets is not
truly attained as a result of the growth along [001] direction.
Then Lou’s group described hierarchical spheres self-
organized from ultrathin anatase TiO2 nanosheets with nearly
100% exposed {001} facets. 40 The thickness of the nanosheets
was estimated to be about 3 nm, which lead to its high specific
surface area of 170 m2 g−1. It was obtained by calcining the
solvothermally synthesized amine-stabilized TiO2 hierarchical
spheres at 400 °C in static air. By taking advantage of both the
high surface activity of {001} surface and the excellent “bulk”
properties imparted by the hierarchical geometry, fast lithium
insertion/deinsertion can be enabled in batteries that mimic
features seen in high-power electrochemical capacitors. The
sheet shaped crystals normally trend to be rolled because of the
atomically unbalanced properties of both sides such as the
occurrence of crystal defects. Thus, the staggered nanosheets is
believed to be more stable than the isolated ones. Yang et al.
also reported a one-pot method to prepare the 3D hierarchical
structures of single-crystalline anatase TiO2 nanosheets
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dominated by well-faceted {001} facets. This synthesis
involves the hydrothermal treatment of the mixed solution of
titanium(IV) butoxide, isobutyl alcohol, HF and deionized
water.41 The formation of unique structure was ascribed to the
presence of isobutyl alcohol as the reaction media, which might
change the growth behaviour of anatase TiO2 nanosheet units
and its mutual interactions as well. Besides, isolated micro-
sized TiO2 nanosheets wholly exposed with high-energy {001}
and {100} facets were synthesized through a solvothermal
route, wherein titanium tetrafluoride was transferred to titanium
oxydifluoride (TiOF2) first and then anatase TiO2 in the
presence of the HF and 1-butanol as the capping agent and
solvent.42, 43 The as-prepared anatase TiO2 nanosheets show a
CrystEngComm Accepted Manuscript
well-faceted morphology and have a unique large size in length
(ca. 4.14 mm) and wholly dominated with high-reactive {001}
and {100} facets, which have percentages of 98.7% and 1.3%,
respectively (Fig. 4). As expected, the as-synthesized products
exhibit superior photocatalytic property in contrast with the
sample with 47% {001} facets. Viewing above reports, almost
all crystals with reactive {001} facets should be assisted by the
incorporation of flonrine and by regulating the reaction
conditions such as the temperature and solvent, anatase crystals
with controlled {001} facets and crystal size can be
successfully achieved.
2.2.2 Anatase TiO2 with other low-index facets
Apart from {001} facet, the common low-index facets for
anatase TiO2 are {101}, {110} and {100} facets. Concerning
the {101} facet is most common and can be readily prepared by
numerous methods,24, 44-46 here we mainly focus on {100} and
{110} surfaces. The {100} facet has a relative low average
surface energy of 0.53 J m-2, which is a slightly higher than that
of {101} surface (0.44 J m-2). Theoretical prediction reveal
{100} facet do not exist in the equilibrium shape of the anatase
crystal according to the Wulff construction, whereas the anatase
TiO2 nanoparticles would become elongated with {100} facets
when oxygen is dominant on the surface.31
In accordance with this prediction, the synthesis by using
titanate as precursor has been developed.47 One typical
example is the hydrothermal treatment of Na-titanate nanotubes
in basic solution, which finally yielded tetragonal nanorods of
single-crystalline anatase TiO2 enclosed by four {100} and
eight {100} facets via a dissolution–nucleation process. Similar
morphology can also achieved by using ammonium as the
crystallographic controlling agent. Shi et al. has conducted the
synthesis of faceted nanorods of anatase TiO2 single crystals
with a large percentage of {100} facets via a hydrothermal
technique. The tetrabutylammonium hydroxide was found to
have important role in the formation of the products: the
selective absorption of ammonium cations and OH anions to
specific facets which change the surface energy of {110} and
{100} facets. As a consequence, the preferential adsorption of
OH anions onto {100} surface favors the formation of O-
terminated {100} and hence stabilizes the {100} face, resulting
in the large percentage of exposed {100} facets.
It can be concluded that using titanate as titanium precursor
and ammonium as capping agents are the most commonly
engaged routes for the synthesis of {100} dominated anatase
crystals, both of which introduce the oxygenated condition for
the exposure of {100} facets. Afterwards, fluorine ions were
also incorporated with specific agents or solvent to prepare
anatase TiO2 crystals enclosed with {100} and {001} facets.
Yang et al. found that cuboid-like anatase TiO2 single crystals
bounded by {001} and {100} facets can be synthesized with
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relatively flat {001} plane of TiO2. As comparison, the crystal

lattice of {101} facet do not match this value which finally
allow the selectively stabilization and formation the {001}
facets.
Because of the large surface energy (1.09 J m−2) for {110}
facet, it has been scarcely been observed compared with the
other low-index facets. Wang et al. have found that anatase
TiO2 crystals with exposed {001} and {110} facets can be
achieved by the incorporation of hydrogen peroxide into the
fluorine system (Fig. 6).51 Hydrogen peroxide is believed to
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react with Ti4+ and form yellow peroxotitanium acid, which can
retard the hydrolysis and influence the surface energy. Further
study by Wu et al. demonstrated 11% of exposed {110} facets

CrystEngComm Accepted Manuscript

by carefully control of the amounts of HF and H2O2, the
reaction temperature and time.52 However, each parameters can
not provide effective means for the stabilizing the {110}
surface, and such surface usually minish upon the hydrothermal
HCl as a synergistic capping agent together with HF (Fig. 5).48 process. Thus, to explore new capping agents are expected and
The roles of HF and HCl for the synthesis of cuboid-like critical for the shape engineering of TiO2 crystals.
anatase TiO2 were studied by theoretical calculations that HCl as
the capping agent at {100} facets is so weakly bounded that it 2.2.2 Anatase TiO2 with high-index facets
may be easily replaced by other agents such as HF. On the
other hand, HCl at {100} surface appears to be much more High-index facets have unique surface atomic structures, such
stable and difficult to be replaced by HF. Therefore, by as a high density of atomic steps, dangling bonds, kinks, and
changing the relative concentrations of HCl and HF, the ledges, that render the excellent capability in clean-energy and
preferred replacement of HCl with HF at {100} and its environmental applications. However, high-index facets present
favorable adsorption provide a unique synergetic effect on the high surface energy and thus grow much faster than the other
formation of anatase TiO2 enclosed by {001} and {100} facets. facets; consequently, they diminish rapidly and disappear
Liu et al. have demonstrated the synthesis of anatase TiO2 during crystal growth. So it is still challenging as well as
crystals with controlled {001}, {101} and {100} facets by attractive to synthesize tailored anatase TiO2 crystals bound by
controlling the relative amount of fluorine and sulfate ions.7 It high-index facets.
was achieved by a tight control over the reaction parameters, In nature, anatase minerals exposed with high-index surface
including the concentration of titanium oxysulfate, the amount scarcely appears, and the experimental synthesis for anatase
of HF and the reaction time. The {100} facet can reach an TiO2 should trace back to recent years. The first growth of
average percentage of 53%, together with 14% of {001} and
33% of {101} facets.
Additionally, anatase TiO2 nanocuboids enclosed by {100}
and {001} facets can also be synthesized through hydrolysis of
titanium tetraisopropoxide in the presence of acetic acid as the
solvent and the ionic liquid 1-butyl-3-methylimidazolium
tetrafluoroborate as the capping agent.49 The ionic liquid is of
significance for the stabilizing of {100} and {001} facets of the
anatase TiO2 nanocuboids. Specifically, it acted as a fluoride
source to release F− ions for stabilizing the {001} facets and
meanwhile, the cation ions acted as capping ions to
preferentially stabilize the {100} facets. This further enabled
the adjustment of the size and aspect ratio of the anatase TiO2
crystals in a wide range by changing the composition
parameters.
Different from the cases by using fluorine, Wang et al.
demonstrated a green synthetic strategy using acid-delaminated
vermiculite and tetramethylammonium hydroxide as synergistic
morphology-controlling agents.50 Interestingly, acid-
delaminated vermiculite is a natural phyllosilicate clay mineral
with low cost. Both agents can facilitate the hydrolysis of
titanium isopropoxide and stabilize the anatase polyanionic
nucleus formed in the early stage of crystal growth.
Experimental results verified that acid-delaminated vermiculite
as the “hard template” would enhance the formation of cube
shaped anatase TiO2 particles from the elongated nanorods. The
exposed external surfaces of the clay layers are covered by Si–
OH groups, and the distance between the bridging Oa atoms
within the hexagonal arrangement is 0.53 nm, which is (b-d) are
fortunately equal to that of the bridging O2c atoms within the

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anatase TiO2 with large percentage {105} facets is based on a
flow field by tuning reaction kinetics.53 But regarding the
thermodynamic control we exemplified here, it will discussed
in the following part. By employing a new titanium precursor,
titanium disilicide, Yang et al. have described a Si doped
anatase TiO2 crystals bound by high-index {201} and high-
energy {001} facets.54 Such crystals enabled the visible-light
induced photocatalytic H2 production, and combined the {110}
and {001} features, offer similar high reactivity to perfect
{001} but are more stable. Si-doped anatase TiO2 with {101}
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and {001} facets were also prepared via the control of reaction
parameters which only presented about half catalytic activity
compared with the anatase TiO2 crystals with high-index facets.
Spindle shaped anatase TiO2 crystals dominated with {301}
facets were also obtained by an alkali metal ion assisted
method, in which sodium titanate acted as the titanium
precursor (Fig. 7a).55 Alkali metals (Li, Na and K) with
different charge density were believed to be attracted to {100}
and {001} planes or single {100} facets, controlling the growth
along the related directions, which eventually leads to the
anisotropic growth with different aspect ratios. However,
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crystals dominated by {101} facets show a superior
photocatalytic activity in decomposing methylene blue to those
with {301} facets. Also by the titanate route, Wang et al.
synthesized spindled shaped anatase TiO2 crystals with exposed
{401} facets (Fig. 7b).56 When urea was added, the spindle
shaped crystals would evolve into truncated tetragonal
bipyramidal particles. This can be explained as that the
hydroxyl ions would preferentially adsorb onto anatase {100}
facets and thus limit the crystal growth along the a and b axes.
As expected, electrochemical performance analyses verified
that the electrochemical performance of TiO2 can be ranked as
{401} > {101} and {001} > {101} facets. Xie et al. has
investigated other agents including ethanol,
CrystEngComm Accepted Manuscript
hexamethylenetetramine and poly(vinyl pyrrolidone) based on
the titanate route.57 They found that hexamethylenetetramine
favors the formation of truncated tetragonal bipyramidal
particles with {001} facets, and when with ethanol, the surface
energy of the {001} surface was reduced and {103} facets were
generated as stepped facets consisting of one unit of {101}
subfacet and one unit of {001} subfacet (Fig. 7d). Similar to
{103} surface, consisting of two units of {101} and one unit of
{001} subfacets, {102} surfaces dominated anatase crystals
were achieved by further adding poly(vinyl pyrrolidone). These
differently shaped TiO2 nanocrystals presented strongly
surface-dependent photocatalytic activity in photodegradation
as well. The photocatalytic sequence of degradation of
methylene blue was {001} and {101} > {102} > {103} and
{101} > {101}.
Overall, almost all the high-index facets exhibit enhanced
surface activities than the common ones, this stresses the
importance of developing feasible ways for the synthesis of
crystals with certain facets, especially the high-index surface.
But its synthetic environment are much more complicated and
relatively ruleless compared with the formation of low-index
facets. On the other hand, kinetics also play an important role in
crystal growth and may provide some insights for the synthesis
of high-index dominated crystal. So it should also be
highlighted and explored as complementary to the
thermodynamic controlled methods.
2.3 Kinetics controlled synthesis
Although Wulff construction has been recognized as the criteria
for thermodynamic equilibrium crystal shapes, in fact, crystal
shapes are usually determined by kinetics rather than by
thermodynamics alone.18 The shapes of growing crystals is also
determined by the net rate of material incorporation into
individual surfaces, such as the solute diffusion in liquid media,
together with their thermodynamics. When the net rate of
material incorporation is constant on each face, a crystal will
evolve toward the steady state shape, at which point growth
proceeds in a self-similar manner. Such steady state growth
shape is generally not equivalent to the equilibrium shape.
A typical kinetics controlled synthetic method of anatase
TiO2 is the high temperature gas-phase reaction approach, in a
process which usually occurs in a vaporization chamber under
the inset and reactant gas flows at high temperature.58 Ohtani
and co-workers (using a special designed reactor) synthesized
the anatase TiO2 with dominated {001} facets via a modified
gas-phase method.59 The vapour of TiCl4 was liberated by
bubbling Ar (200 mL/min) into a TiCl4 solution at 358 K,
mixing it with an O2 stream (1200 mL/min), and fed into a
quartz glass tube heated from the outside by an oxyhydrogen
flame burner. The tube was rotated around the cylindrical axis
at a speed of 55 r/min for homogeneous heating with heating
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temperature of 1573 K. The low concentration of TiCl4 and the
narrow heating zone would prevent formation of large particles
and polycrystalline aggregates with grain boundaries, and thus
the size of anatase TiO2 particles with {001} facets is about 100
nm, which is much smaller than that prepared by hydrothermal
reaction of TiF4 (>1 µm).33
In another approach by Yang et al., a straight static furnace
pipe and a thin spiral tube were used as reactor and reactant
feeder and the vapor-phase TiCl4 was liberated by bubbling O2
into TiCl4 liquid and then passed through the furnace pipe.53
Under this flow field, anatase TiO2 crystals with predominantly
exposed high-index {105} facets can be achieved. Interestingly,
high oxygen flow (0.5 L min-1) can lead to the formation of
anatase TiO2 crystals with irregular shape and broad particle
size distribution, while low oxygen flow (0.2–0.4 L min-1) can
generate anatase crystals dominated by {105} facets. Anatase
TiO2 crystals with {001} facets can also be obtained by the
careful control of the flow field. A copper-based cool-water
tube was further introduced into the central part of the furnace
pipe to quench the temperature of the growing anatase TiO2
single crystals attached to the surface to obtain the intermediate
products. It was found that the crystal growth should follow a
two-stage growth mechanism. Well-faceted anatase TiO2 single
crystals with a highly truncated morphology were formed
initially bounded with {101} and {001} facets which is similar
to the Ohtani’s results (Fig. 8). Then high-index facets
including {107} and {105} started to appear along some
crystalline “tips” on the existing {001} facets. This implies that
the anatase TiO2 crystals in this case are not thermodynamically
equilibrium shape which is determined by the combined effect
of lattice matching principle of epitaxial processes and the
reaction kinetics of gas-phase reaction. Then by using dual
source, Sn doped TiO2 dominated with {105} facets was
synthesized by the same gas phase oxidation technique.60 The
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small amount of doped Sn in TiO2 could suppress the
recombination of photogenerated electron–hole pairs which
lead to significantly enhanced photocatalytic hydrogen
evolution performance, with its hydrogen generation rate being
4.5 times higher than that of pure TiO2.
On the basis of the synthetic methods we exemplified
above, kinetics controlled strategy is an alternative or
complementary way to achieve specific crystal shapes, but the
combination of both thermodynamic and kinetics should
provide new perspectives for the design and growth of new
artificial crystals.
2.4 Bio-inspired synthesis
As a natural pathway by assembling biogenic inorganic
compounds, biomineralization have hold promise for exploiting
unique, effective strategies to fabricate unique functional
materials. An ocean of inorganic nanostructures have been
developed with the aid of specific interactions between organic
moieties and biocompatible inorganic minerals.61, 62 The most
typical example is the complex single crystalline calcitic
skeleton. Aizenberg et al. have described a bio-inspired
approach to growing millimetre sized single calcite crystals
with sub-10-µm patterns and controlled crystallographic
orientation. Micropatterned template was used as sites for stress
and impurity release during the amorphous-to-crystalline
transition of calcite crystals, and more importantly, the
framework was functionalized with HS(CH2)nA (A = OH,
CO2H, SO3H) to trigger the oriented nucleation and
crystallization. Although the explicit role of the absorbed
molecular or groups on the crystal surface are not well
understood, this showed resemblance to the complicated effect
of live organisms in biomineralization.
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Then taking advantage of the synergistic behaviour of co-
capping agents of organic citric acid and inorganic HF, a new
class of crystal surface of TiO2 has been demonstrated, which is
enclosed by quasi continuous high-index microfacets and thus
has a unique truncated biconic morphology.63 That is, crystal
growth rates of all facets between two normal {101} and {011}
crystal surfaces are almost identical as the first report of a non-
confinement growth for artificial crystals. With the addition of
citric acid, bipyramidal-shaped TiO2 single crystals evolved
along the crystal edges between the two {101} facets to form
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additional {112} facets and then extended gradually into
continuous high-index facets (Fig. 9). Other organic capping
agents are also attempted which also gave rise to curved
crystals but in the rutile crystalline phase. Through theoretical
calculations, continuous bending of the external crystal surface
was found to be correlated with the synergistic effects of
chemisorbed HF and citric acid and, particularly, the unique
adsorption mode of organic citric acid that favours its
attachment to high-index facets. This bio-inspired method may
not only develop a new family of functional crystals with a
non-flat surface, but also pave the way for the artificial
synthesis of unique structures which can only been obtained by
organic organisms.
3. Biomedical applications
To date, the shape engineering of anatase TiO2 has achieve
great advancement in physicochemical applications especially
photocatalysis and solar cells, which has been intensively
reviewed.109 In addition, TiO2 based materials also enable many
biomedical applications, such as photodynamic therapy for
cancer, drug delivery system, cell imaging, biosensors for
biological assay and genetic engineering.64 Through the studies
of crystal shape engineering in this field are at the initial stage,
these tailored anatase TiO2 crystals have many success in
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disease diagnosis65, 66 and drug monitor.67, 68 Thus we will
highlight the strength of shape engineering of anatase TiO2
crystals in biomedical applications which may be as a candidate
tool for the further advances in this field.
Anatase TiO2 have been utilized for electrochemical
detection of dopamine,69 tryptophan,70 aripiprazole,71 uric
acid,72 ascorbic acid,73 glucose,74 O6-benzylguanine,75 6-
Phosphate aminopurine,76 adenine77 and guanine.77 Surface
characteristic is an crucial parameter for the selection and
development of the sensing materials. Based on different
functional activities for different purposes, these
electrochemical biosensors of anatase TiO2 with facets can be
classified into two types: disease diagnosis and drug monitor.
3.1 Disease diagnosis
Dopamine (DA) acts as a key neurotransmitter in the brain that
influences the central nervous function,78 attention span,79
cognition,80 emotions81 and neuronal plasticity.82 The network
of neurotransmitters involves transmission of messages
between neurons.83 Hence, disturbance in the dopaminergic
system can cause neurological disorders in the human body.84
DA deficiency in the mammalian central nervous system could
lead to the Parkinson's disease,85, 86 schizophrenia,87 drug
addiction.88 Therefore, to monitor and diagnose these diseases,
level of DA must be effectively measured.
Due to the high electrochemical activity of DA,
electrochemical methods have been widely explored for DA
detection.89 However, DA usually coexists with ascorbic acid
(AA) and uric acid (UA) in biological tissues at a low
concentration (0.01–1 µM).90, 91 At conventional electrodes,
these electroactive species (DA and AA) have an overlapping
voltammetric response, resulting in low selectivity and poor
sensitivity.92 Thus, developing a modified electrode with high
sensitivity and good selectivity is essential for efficient
electrochemical detection of DA concentration.
In recent years, TiO2 has been predominantly employed as
an electrode material in electrochemical biosensors for the
detection of various analytes even at low concentration because
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of its good biocompatibility and catalytic properties.93-95 In
these electrochemical biosensors, TiO2 was employed as
support matrix for immobilizing enzymes, which can facilitate
the direct electron transfer and enhance the catalytic activity of
enzymes. Meanwhile, graphene has been equally regarded as an
attractive material. Its hybridization with TiO2 as a
nanocomposite for DA sensing has gained immense interest, as
it offers improved electron transfer and excellent
electrocatalytic activity towards the oxidation of DA and
distinguishability between DA and relevant interference
materials70. Y. Fan et al.96 developed a facile hydrothermal
method to fabricate TiO2–graphene nanocomposite. The
structure characterization results suggested that hydrothermal
reaction proceeded with efficient crystallization of TiO2 in
anatase phase and situimmobilization on graphene substrate.
Subsequently, the TiO2–graphene modified glassy carbon
electrode (GCE) exhibited favorable electron transfer kinetics
and electrocatalytic activity towards the oxidation of DA.
Furthermore, the coexisting electroactive species such as DA,
AA and UA gave well resolved voltammetric responses at the
TiO2–graphene–GCE, and DA can be detected with high
sensitivity and good selectivity.
According to the Wulff construction,33 most available
anatase TiO2 crystals are dominated by the thermodynamically
stable {101} facets. However, the surface energy estimated for
the {101} facets of anatase TiO2 is significantly lower than that
of the {001} facets.97 And, recent studies even showed that
increasing the exposed {001} facets of TiO2 leads to better
performance in photocatalysis owing to the improved activity
of TiO2.40, 98 In this regard, How GTS et al. tried to develop
graphene-TiO2 nanocomposite with highly exposed {001}
facets for DA sensing application (Fig. 10).99 They introduced a
simple synthetic route to prepare a reduced graphene oxide
(rGO) decorated TiO2 nanocomposite with highly exposed
{001} facets. Consequently, the rGO/TiO2 nanocomposite
modified GCE exhibited enhanced electrochemical
performance in detection of DA with satisfactory sensitivity
and selectivity.
In addition to TiO2–graphene nanocomposites, electrode
surfaces modified with the noble metal particles have also been
studied for enhancing the overall electro-catalytic reactivity of
TiO2. 100-102 For example, Hosseini et al. prepared Au/TiO2/Ti
electrodes by galvanic deposition of gold particles from an
acidic bath containing KAu(CN)2 in the presence of a citrate
buffer onto TiO2 nanotubes layer on titanium substrates.101
Subsequently, the electro-catalytic activity of Au/TiO2/Ti
electrodes for the dopamine electro-oxidation was studied by
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cyclic voltammetry and differential pulse voltammetry. And,
the Au/TiO2/Ti electrodes exhibited a considerably higher
electro-catalytic activity toward the oxidation of dopamine.
Finally, the oxidation current of dopamine Au/TiO2/Ti
electrodes was used for the determination of dopamine in
aqueous solution and a linear calibration was found in the range
of 0.5–2.5 mM with a correlation coefficient of 0.99. Therefore,
this electrode modified with the noble metal particles can also
be used for quantitative determination of dopamine in disease
diagnosis.
3.2 Drug monitor
CrystEngComm Accepted Manuscript
Although therapeutic options have multiplied, therapy for
cancer is still a challenge nowadays,103-105 and thus, cancer
therapy warrants new strategy. The DNA repair protein, O6-
alkyl-guanine DNA alkyltransferase (AGT), is highly expressed
in solid tumors, and confers tumor resistance to a variety of
anticancer alkylating agents.106 Fortunately, O6-benzylguanine
(O6BG) is a very effective inactivator of AGT, blinding AGT
rapidly.107 O6BG provides an equally effective treatment of
cancers either alone or in combination with other anticancer
drugs.106 Thus, the antineoplastic drug O6BG is usually used in
clinical cancer treatment, such as T-cell lymphoma109, breast
cancer110 and malignant gliomas111. Therefore, the detection of
O6BG and its effect on cancer cells are essential to cancer
diagnosis, treatment and molecular biology research.
Anatase TiO2 is a semiconductor with a wide band gap (3.2
eV), and the band gap usually increases with decreasing size of
the anatase domains, which strongly influences the charge
transfer dynamics due to its increasing resistance.112 Thus,
nanoscale engineering represents an effective route to the
enhancement of the charge transport dynamics involved, such
as the formation of nanoscale heterostructures with a different
semiconductor.75, 76 To explore electrochemical analysis of
O6BG and its effect on lung cancer cells, Cui et al. constructed
nano-p-n junction heterostructures based on TiO2 nanobelts
with enhanced {001} facets by assembling p-type
semiconductor NiO nanoparticles on n-type surface-coarsened
TiO2 nanobelt surfaces (Fig. 11). 72, 76 The heterostructures were
then used as the sensing electrode for the electrochemical
detection of O6BG and lung cancer cells. Subsequently, O6BG
exhibited an irreversible diffusion-controlled electrochemical
process with an oxidation peak clearly identified at +0.78 V.
For lung cancer cells, one oxidation peak was found at +1.1 V
and two reduction peaks at +0.30, and +0.90 V. These
voltammetric features disappeared when O6BG was added to
the lung cancer cells, which was ascribed to the structural
changes of the cell membranes caused by the anticancer drug.
In 2014, Cui et al. successfully applied nano-p-n junction
heterostructures enhanced TiO2 nanobelts for the
electrochemical detection of 6-Phosphate aminopurine (6PA)
which is an integral part of nucleic acids.76 Since 6PA
participates in the synthesis of RNA and DNA in vivo, it can
effectively stimulate interleukin proliferation, increasing white
blood cells, and can be used in leukopenia from chemotherapy,
radiation therapy, and benzene poisoning.113, 114 In this regard,
6
PA is usually used in clinical anticancer treatment and
biochemical research. However, the electrochemical analysis of
6
PA has remained largely unexplored. As illustrated by Cui et
al. the nanobelt-functionalized electrodes enclosed with {001}
facets had a markedly enhanced electrocatalytic activity and
sensitivity in the oxidation of 6PA.76 The enhanced performance
is most likely due to the nano-p–n junctions and the uniform
distribution of the NiO nanoparticles on the TiO2 nanobelt
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surface that effectively improved charge transport at the
interface. These results demonstrated that nano-p-n junction
heterostructures based on TiO2 nanobelts might serve as
promising candidates for biosensing applications of anticancer
drugs that will be of significance in cancer diagnosis, treatment
and molecular biology research.
3.3 Toxicity
However, the cytotoxicity and genotoxicity of TiO2 have also
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caused wide concerns by researchers in recent years.113-120 The
toxic effects of anatase TiO2 are not only associated with the
particle size, but also closely related to the surface reactivity of
the nanocrystal.118 Zhang et al. developed anatase TiO2 single-
crystals with 27-50% chemically reactive {001} facets by using
a microwave-assisted method （Fig. 12）.92 Subsequently, the
products exhibited excellent photocatalytic efficiency for both
oxidation of nitric oxide in air and degradation of organic
compounds in aqueous solution under UV light irradiation.
Furthermore, the TiO2 single-crystals with 50% {001} facets
were found to be nontoxic using Zebrafish (Danio rerio) as a
model. These results illustrate a survival rate of virtually 100%
even under the highest concentration 1000 ppb and 96 h
exposure.
4. Conclusions
Shape engineering of crystal is of paramount importance for the
synthesis of high-quality materials with well-defined surface
properties. From the perspectives of thermodynamics and
kinetics, we highlight the crystal shape engineering of anatase
TiO2 crystal based on which common low-index faces as well
as the high-index facets can be achieved. Beyond this, the bio-
inspired technique is also highlighted which would open a new
field for the growth of new types of materials. The
corresponding biomedical applications of tailored TiO2 crystals
are concluded which illustrated the power of crystal shape
engineering for the bio-related applications.
Despite the rapid development of the theoretical predictions
as well as the experimental results for the anatase TiO2 with
tailored facets in the recent years, many challenges exist in
several aspects. For instance, the thermodynamics controlled
method generally relied on the absorbing of capping agents,
which stabilize specific facet by reducing its relative surface
energy. The absorption can be spontaneously occurred, this
possibly give rise to other crystalline phases. A typical example
is the synthesis of curved crystals.63 When glycolic acid, lactic
acid or malic acid were used, crystals in rutile phase were
emerged, whereas with the similar molecular structure, citric
acid can generate anatase crystals. In this respect, tracking of
possible reason of these crystalline phase formation is
necessary, especially based on the surface absorption behaviour
at the atomic or molecular scale. Furthermore, searching for
other capping agents is also an urgent issue for the
thermodynamics controlled route. Concerning the high-reactive
facets are often obtained by F-containing capping agents, which
is quite toxic and corrosive, the usage of capping agents with
reduced or no fluorine containing compounds are highly
desired. The more complex capping agents or mixed synthetic
system might be also practical solutions to create anatase TiO2
crystals with tailored facets.
The kinetics controlled and bio-inspired routes are relative
rare in literature, but may provide more opportunities for crystal
shape engineering in the future. To our knowledge, anatase
dominated with {105} facets has still not been obtained by
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using appropriate capping agents while the kinetics controlled
technique can make it. The key problem in the kinetics route is
how to model and design the flow or liquid field, and then
optimize the experimental parameters and improve the crystal
yields. As comparison, the bio-inspired method would be more
attractive in view of the unique crystalline structures stemmed
from nature. For example, the skeleton of a brittlerstar is
composed of a single calcite crystal with regular inner pores
which is derived from the biological organism. State-of-the-art,
mesoporous single crystal structure can only be synthesized by
a complicated methods with multiple steps,121 which reversely
emphasize the importance of learning and simulating from the
natural biomineralization.
CrystEngComm Accepted Manuscript
For biomedical applications, TiO2 crystals with tailored
facets have offered a host of approaches to electrochemical
biosensors, such as disease diagnosis and drug monitor. As
discussed in the previous sections, graphene-TiO2
nanocomposite with highly exposed {001} and {101} facets
both exhibited satisfactory electrochemical performance in
detection of DA with high sensitivity and good selectivity.95, 98
But more symmetric characterisations and other facets are still
absent in literature which is broad soil for the biomedical
applications of anatase TiO2 crystals. However, in addition to
electrochemical biosensors, TiO2 based materials have been
also been utilized for antibacterial therapy,12 photodynamic
therapy,13 sonodynamic therapy,14 drug delivery system,15 cell
imaging16 and genetic engineering.17 Almost all these are
closely related to the surface properties or crystal geometries
and thus, crystal shape engineering of anatase TiO2 is truly
valuable in an attempt to give promising progress in biomedical
applications.
Acknowledgements
This work was financially supported by National Natural
Science Foundation of China (21373083, 30973968), SRF for
ROCS, SEM, SRFDP, Programme for Professor of Special
Appointment (Eastern Scholar) at Shanghai Institutions of
Higher Learning.
Notes and references
a
Key Laboratory for Ultrafine Materials of Ministry of Education, School
of Materials Science and Engineering, East China University of Science
and Technology, 130 Meilong Road, Shanghai 200237, China.
E-mail: hgyang@ecust.edu.cn;
b
Changhai Hospital of Traditional Chinese Medicine, Second Military
Medical University, 168 Changhai Road, Shanghai, 200433 China.
E-mail: suyh@smmu.edu.cn;
† These authors contributed equally to this work.
1. A. Fujishima and K. Honda, Nature, 1972, 238, 37-38.
2. Z. Wang, S. Ran, B. Liu, D. Chen and G. Shen, Nanoscale, 2012,
4, 3350-3358.
3. R. Zhang, A. A. Elzatahry, S. S. Al-Deyab and D. Zhao, Nano
Today, 2012, 7, 344-366.
4. J. Zhu, J. Wang, F. Lv, S. Xiao, C. Nuckolls and H. Li, J. Am.
Chem. Soc., 2013, 135, 4719-4721.
5. S. Yang, Y. C. Zheng, Y. Hou, X. H. Yang and H. G. Yang, Phys.
Chem. Chem. Phys., 2014, 16, 23038-23043.
6. B. O'regan and M. Gratzel, Nature, 1991, 353, 737-740.
7. J. Pan, G. Liu, G. Q. Lu and H.-M. Cheng, Angew. Chem. Int. Ed.,
2011, 123, 2181-2185.
8. S. Yang, Y. Hou, B. Zhang, X. H. Yang, W. Q. Fang, H. J. Zhao
and H. G. Yang, J. Mater. Chem. A, 2013, 1, 1374-1379.
This journal is © The Royal Society of Chemistry 2012
 Page 11 of 13 CrystEngComm
View Article Online
CrystEngComm ARTICLE
DOI: 10.1039/C5CE00804B

9. Y. Shuang, Y. Hou, B. Zhang and H. G. Yang, Ind. Eng. Chem. 45. Y. Qiu, W. Chen and S. Yang, Angew. Chem. Int. Ed., 2010, 49,
Res., 2013, 52, 4098–4102. 3675-3679.
10. B. Wu, C. Guo, N. Zheng, Z. Xie and G. D. Stucky, J. Am. Chem. 46. J.-W. Shiu, C.-M. Lan, Y.-C. Chang, H.-P. Wu, W.-K. Huang and
Soc., 2008, 130, 17563-17567. E. W.-G. Diau, ACS Nano, 2012, 6, 10862–10873.
11. D. Wang, D. Choi, J. Li, Z. Yang, Z. Nie, R. Kou, D. Hu, C. 47. J. Li and D. Xu, Chem. Commun., 2010, 46, 2301-2303.
Wang, L. V. Saraf, J. Zhang, I. A. Aksay and J. Liu, ACS Nano, 48. L. Wu, B. X. Yang, X. H. Yang, Z. G. Chen, Z. Li, H. J. Zhao, X.
2009, 3, 907-914. Q. Gong and H. G. Yang, CrystEngComm, 2013, 15, 3252-3255.
12. D. M. Tobaldi, C. Piccirillo, R. C. Pullar, A. F. Gualtieri, M. P. 49. X. Zhao, W. Jin, J. Cai, J. Ye, Z. Li, Y. Ma, J. Xie and L. Qi, Adv.
Seabra, P. M. Castro and J. A. Labrincha, J. Phys. Chem. C, 2014, Funct. Mater., 2011, 21, 3554-3563.
118, 4751-4766. 50. L. Wang, L. Zang, J. Zhao and C. Wang, Chem. Commun., 2012,
13. M. Ganguly, S. K. Mukhopadhyay, S. Karthik, S. Barman and P. 48, 11736-11738.
Published on 09 July 2015. Downloaded by University of Prince Edward Island on 12/07/2015 08:51:47.

N. Singh, MedChemComm, 2015, DOI: 10.1039/C4MD00497C. 51. M. Liu, L. Piao, L. Zhao, S. Ju, Z. Yan, T. He, C. Zhou and W.
14. P. Qiu, W. Li, K. Kang, B. Park, W. Luo, D. Zhao and J. Khim, J. Wang, Chem. Commun., 2010, 46, 1664-1666.
Mater. Chem. A, 2014, 2, 16452-16458. 52. Q. Wu, Z. Wu, Y. Li, H. Gao, L. Piao, T. Zhang and L. Du,

CrystEngComm Accepted Manuscript

15. Y. Du, W. Ren, Y. Li, Q. Zhang, L. Zeng, C. Chi, A. Wu and J. Chinese J. Catal., 2012, 33, 1743-1753.
Tian, J. Mater. Chem. B, 2015. 53. H. B. Jiang, Q. Cuan, C. Z. Wen, J. Xing, D. Wu, X.-Q. Gong, C.
16. J. Bai, Y. Zhao, Z. Wang, C. Liu, Y. Wang and Z. Li, Anal. Li and H. G. Yang, Angew. Chem. Int. Ed., 2011, 123, 3848-3852.
Chem., 2013, 85, 4813-4821. 54. L. Wu, H. B. Jiang, F. Tian, Z. Chen, C. Sun and H. G. Yang,
17. T. Tachikawa, Y. Asanoi, K. Kawai, S. Tojo, A. Sugimoto, M. Chem. Commun., 2013, 49, 2016-2018.
Fujitsuka and T. Majima, Chem.- Eur. J., 2008, 14, 1492-1498. 55. M.-H. Yang, P.-C. Chen, M.-C. Tsai, T.-T. Chen, I. C. Chang, H.-
18. M. A. Lovette, A. R. Browning, D. W. Griffin, J. P. Sizemore, R. T. Chiu and C.-Y. Lee, CrystEngComm, 2013, 15, 2966-2971.
C. Snyder and M. F. Doherty, Ind. Eng. Chem. Res., 2008, 47, 56. X. Han, F. Zhou, L. Li and C. Wang, Chem. – Asian J., 2013, 8,
9812-9833. 1399-1403.
19. G. Wulff, Z Kristallogr, 1901, 34, 449-530. 57. X. Han, B. Zheng, J. Ouyang, X. Wang, Q. Kuang, Y. Jiang, Z.
20. U. Diebold and Ulrike, Surf. Sci. Rep., 2003, 48, 53-229. Xie and L. Zheng, Chem. – Asian J., 2012, 7, 2538-2542.
21. M. Lazzeri, A. Vittadini and A. Selloni, Phys. Rev. B, 2001, 63, 58. H.-B. Jiang, L.-F. Pan, P.-F. Liu, W.-Q. Fang and H.-G. Yang,
155409. Chinese Sci. Bull., 2014, 59, 2135-2143.
22. F. Amano, T. Yasumoto, O.-O. Prieto-Mahaney, S. Uchida, T. 59. F. Amano, O.-O. Prieto-Mahaney, Y. Terada, T. Yasumoto, T.
Shibayama and B. Ohtani, Chem. Commun., 2009, 2311-2313. Shibayama and B. Ohtani, Chem. Mater., 2009, 21, 2601-2603.
23. C.-T. Dinh, T.-D. Nguyen, F. Kleitz and T.-O. Do, ACS Nano, 60. H. B. Jiang, J. Xing, Z. P. Chen, F. Tian, Q. Cuan, X.-Q. Gong
2009, 3, 3737-3743. and H. G. Yang, Catal. Today, 2014, 225, 18-23.
24. C. Chen, R. Hu, K. Mai, Z. Ren, H. Wang, G. Qian and Z. Wang, 61. E. Bäuerlein, Angew. Chem. Int. Ed., 2003, 42, 614-641.
Cryst. Growth. Des., 2011, 11, 5221–5226. 62. E. Dujardin and S. Mann, Adv. Mater., 2002, 14, 775.
25. S. Yang, Y. C. Zheng, Y. Hou and H. G. Yang, ChemPlusChem, 63. S. Yang, B. X. Yang, L. Wu, Y. H. Li, P. Liu, H. Zhao, Y. Y. Yu,
2015, DOI: 10.1002/cplu.201402449. X. Q. Gong and H. G. Yang, Nat. Commun., 2014, 5, 6355.
26. A. Vittadini, A. Selloni, F. P. Rotzinger and M. Grätzel, Phys. 64. Y. Zi Fei, W. Long, G. Hua, Y. Yang and S. Hua, Phys. Chem.
Rev. Lett., 1998, 81, 2954-2957. Chem. Phys., 2013, 15, 4844-4858.
27. Diebold and Ulrike, Appl. Phys. A-Mater., 2002, 76, 1-7. 65. A. Ravalli and G. Marrazza, J. Nanosci. Nanotechno., 2015, 15,
28. R. Hengerer, B. Bolliger, M. Erbudak and M. Grätzel, Surf. Sci., 3307-3319.
2000, 460, 162-169. 66. L. Eggeling, M. Bott and J. Marienhagen, Curr. Opin. Biotech.,
29. Y. Yin and A. P. Alivisatos, Nature, 2004, 437, 664-670. 2015, 35, 30-36.
30. J. C. Yu, Yu, Ho, Jiang and Zhang, Chem. Mater., 2002, 14, 67. M. A. Cooper, Nat. Rev. Drug Discov., 2002, 1, 515-528.
3808-3816. 68. T. Wang, M.-B. Wu, Z.-J. Chen, H. Chen, J.-P. Lin and L.-R.
31. A. S. Barnard and L. A. Curtiss, Nano Letters, 2005, 5, 1261- Yang, Curr. Pharm. Biotechno., 2015, 16, 11-25.
1266. 69. P. Gao, H. Ma, J. Yang, D. Wu, Y. Zhang, B. Du, D. Fan and Q.
32. K. F. Zmbov and J. L. Margrave, J. Phys. Chem., 1967, 71, 2893- Wei, New J. Chem., 2015, 39, 1483-1487.
2895. 70. C.-X. Xu, K.-J. Huang, Y. Fan, Z.-W. Wu, J. Li and T. Gan, Mat.
33. H. G. Yang, C. H. Sun, S. Z. Qiao, J. Zou, G. Liu, S. C. Smith, H. Sci. Eng. C, 2012, 32, 969-974.
M. Cheng and G. Q. Lu, Nature, 2008, 453, 638-641. 71. R. Shrivastava, S. Saxena, S. Satsangee and R. Jain, Ionics, 2015,
34. G. Liu, H. G. Yang, X. Wang, L. Cheng, H. Lu, L. Wang, G. Q. 1-11.
Lu and H.-M. Cheng, J. Phys. Chem. C, 2009, 113, 21784-21788. 72. A. R. Rajamani, R. Kannan, S. Krishnan, S. Ramakrishnan, S. M.
35. X. Han, Q. Kuang, M. Jin, Z. Xie and L. Zheng, J. Am. Chem. Raj, D. Kumaresan, N. Kothurkar and M. Rangarajan, J. Nanosci.
Soc., 2009, 131, 3152-3153. Nanotechno., 2015, 15, 5042-5047.
36. X. H. Yang, Z. Li, G. Liu, J. Xing, C. Sun, H. G. Yang and C. Li, 73. S. Zhu, H. Li, W. Niu and G. Xu, Biosens. Bioelectron., 2009, 25,
CrystEngComm, 2011, 13, 1378-1383. 940-943.
37. X. H. Yang, Z. Li, C. Sun, H. G. Yang and C. Li, Chem. Mater., 74. S. J. Bao, C. M. Li, J. F. Zang, X. Q. Cui, Y. Qiao and J. Guo,
2011, 23, 3486-3494. Adv. Funct. Mater., 2008, 18, 591-599.
38. S. Yang, Y. Hou, B. Zhang, X. H. Yang, H. Zhang, H. J. Zhao and 75. J. Cui, Y. Ge, S. Chen, H. Zhao, H. Liu, Z. Huang, H. Jiang and J.
H. G. Yang, CrystEngComm, 2014, 16, 7502-7506. Chen, J. Mater. Chem. B, 2013, 1, 2072-2077.
39. A. S. Ichimura, B. M. Mack, S. M. Usmani and D. G. Mars, 76. J. Cui, S. Chen, H. Liu and Z. Huang, J. Solid State Electr., 2014,
Chem. Mater., 2012, 24, 2324-2329. 18, 2693-2699.
40. J. S. Chen, Y. L. Tan, C. M. Li, Y. L. Cheah, D. Luan, S. 77. Y. Fan, K.-J. Huang, D.-J. Niu, C.-P. Yang and Q.-S. Jing,
Madhavi, F. Y. C. Boey, L. A. Archer and X. W. Lou, J. Am. Electrochim. Acta, 2011, 56, 4685-4690.
Chem. Soc., 2010, 132, 6124-6130. 78. O. Hornykiewicz, Pharmacol. Rev., 1966, 18, 925-964.
41. W. Q. Fang, J. Z. Zhou, J. Liu, Z. G. Chen, C. Yang, C. H. Sun, 79. A. Nieoullon, Prog. Neurobiol., 2002, 67, 53-83.
G. R. Qian, J. Zou, S. Z. Qiao and H. G. Yang, Chem. –Eur. J., 80. N. Erixon-Lindroth, L. Farde, T.-B. R. Wahlin, J. Sovago, C.
2011, 17, 1423-1427. Halldin and L. Bäckman, Psychiat. Res. Neuroim., 2005, 138, 1-
42. C. Z. Wen, J. Z. Zhou, H. B. Jiang, Q. H. Hu, S. Z. Qiao and H. 12.
G. Yang, Chem. Commun., 2011, 47, 4400-4402. 81. A. L. Terzian, F. Drago, C. T. Wotjak and V. Micale, Front.
43. C. Z. Wen, Q. H. Hu, Y. N. Guo, X. Q. Gong, S. Z. Qiao and H. Behav. Neurosci., 2011, 5, 49.
G. Yang, Chem. Commun., 2011, 47, 6138-6140. 82. S. R. Jones, R. R. Gainetdinov, M. Jaber, B. Giros, R. M.
44. Y.-w. Jun, M. F. Casula, J.-H. Sim, S. Y. Kim, J. Cheon and A. P. Wightman and M. G. Caron, P. Nat. Acad. Sci., 1998, 95, 4029-
Alivisatos, J. Am. Chem. Soc., 2003, 125, 15981-15985. 4034.

This journal is © The Royal Society of Chemistry 2012 J. Name., 2012, 00, 1-3 | 11
 CrystEngComm Page 12 of 13
View Article Online
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83. E. S. Bromberg-Martin, M. Matsumoto and O. Hikosaka, Neuron, 117. T. Coccini, S. Grandi, D. Lonati, C. Locatelli and U. De Simone,
2010, 68, 815-834. Neurotoxicology, 2015, 48, 77-89.
84. T. V. Maia and M. J. Frank, Nat. Neurosci., 2011, 14, 154-162. 118. T. Chen, J. Yan and Y. Li, J. Food Drug Anal., 2014, 22, 95-104.
85. M. Matsumoto, Movement Disord., 2015, DOI: 119. W. Miao, B. Zhu, X. Xiao, Y. Li, N. B. Dirbaba, B. Zhou and H.
10.1002/mds.26177. Wu, Aquat. Toxicol., 2015, 161, 117-126.
86. J. Zhang, Y.-z. Ma and X.-m. Shen, J. Integr. Med., 2013, 11, 120. D. B. Warheit, R. A. Hoke, C. Finlay, E. M. Donner, K. L. Reed
285-290. and C. M. Sayes, Toxicology letters, 2007, 171, 99-110.
87. O. Howes, R. McCutcheon and J. Stone, J. Psychopharmacol., 121. E. J. W. Crossland, N. Noel, V. Sivaram, T. Leijtens, J. A.
2015, 29, 97-115. Alexander-Webber and H. J. Snaith, Nature, 2013, 495, 215-219.
88. G. Di Chiara, V. Bassareo, S. Fenu, M. A. De Luca, L. Spina, C.
Cadoni, E. Acquas, E. Carboni, V. Valentini and D. Lecca,
Published on 09 July 2015. Downloaded by University of Prince Edward Island on 12/07/2015 08:51:47.

Neuropharmacology, 2004, 47, 227-241.

89. B. J. Venton and R. M. Wightman, Anal. Chem., 2003, 75, 414-
421.

CrystEngComm Accepted Manuscript

90. J.-M. Zen and P.-J. Chen, Anal. Chem., 1997, 69, 5087-5093.
91. L. Yang, D. Liu, J. Huang and T. You, Sensor. Actuat. B Chem.,
2014, 193, 166-172.
92. H. Wang, P. Jiang, X. Bo and L. Guo, Electrochimica Acta, 2012,
65, 115-121.
93. D. Zhang, G. Li, H. Wang, K. M. Chan and J. C. Yu, Cryst.
Growth Des., 2010, 10, 1130-1137.
94. G. B. Soares, C. M. Vaz, C. Ribeiro and I. Hermans,
Electrocatalysis, 2015, 6, 92-101.
95. J. Wang, G. Xu, X. Zhang, J. Lv, X. Zhang, Z. Zheng and Y. Wu,
Dalton T., 2015.
96. Y. Fan, H.-T. Lu, J.-H. Liu, C.-P. Yang, Q.-S. Jing, Y.-X. Zhang,
X.-K. Yang and K.-J. Huang, Colloid. Surface. B, 2011, 83, 78-
82.
97. J. HongáPan, Chem. Commun., 2011, 47, 6942-6944.
98. L. Gu, J. Wang, H. Cheng, Y. Zhao, L. Liu and X. Han, ACS
Appl. Mater. Inter., 2013, 5, 3085-3093.
99. G. T. S. How, A. Pandikumar, H. N. Ming and L. H. Ngee, Sci.
Rep., 2014, 4, 5044.
100. M. Hosseini, M. M. Momeni and M. Faraji, J. Mater. Sci., 2010,
45, 2365-2371.
101. M. Hosseini, M. M. Momeni and M. Faraji, J. Appl. Electrochem.,
2010, 40, 1421-1427.
102. M. Hosseini and M. M. Momeni, J. Solid State Electr., 2010, 14,
1109-1115.
103. G. A. Masters, L. Krilov, H. H. Bailey, M. S. Brose, H. Burstein,
L. R. Diller, D. S. Dizon, H. A. Fine, G. P. Kalemkerian and M.
Moasser, J. Clin. Oncol., 2015, 12, 331-335.
104. C.-q. Ling, X.-q. Yue and C. Ling, J. Integr. Med., 2014, 12, 331-
335.
105. C. E. DeSantis, C. C. Lin, A. B. Mariotto, R. L. Siegel, K. D.
Stein, J. L. Kramer, R. Alteri, A. S. Robbins and A. Jemal, CA-
Cancer J. Clin., 2014, 64, 252-271.
106. M. E. Dolan, R. C. Moschel and A. E. Pegg, P. Natl. Acad. Sci.,
1990, 87, 5368-5372.
107. M. E. Dolan, Adv. Drug Deliver. Rev., 1997, 26, 105-118.
108. S. D. Konduri, J. Ticku, G. C. Bobustuc, R. M. Sutphin, J. Colon,
B. Isley, K. K. Bhakat, S. S. Kalkunte and C. H. Baker, Clin.
Cancer Res., 2009, 15, 6087-6095.
109. N. Apisarnthanarax, G. S. Wood, S. R. Stevens, S. Carlson, D. V.
Chan, L. Liu, S. K. Szabo, P. Fu, A. C. Gilliam and S. L. Gerson,
Archives of dermatology, 2012, 148, 613-620.
110. S. Jeudy, K. S. Srivenugopal and S. D. Konduri, Cancer Res.,
2012, 72, 3721-3721.
111. K. E. Warren, S. Gururangan, J. R. Geyer, R. E. McLendon, T. Y.
Poussaint, D. Wallace, F. M. Balis, S. L. Berg, R. J. Packer and S.
Goldman, J. Neuro. Oncol., 2012, 106, 643-649.
112. X. Chen and S. S. Mao, Chem. Rev., 2007, 107, 2891-2959.
113. B. Mohelnikova-Duchonova, L. Marsakova, D. Vrana, I.
Holcatova, M. Ryska, Z. Smerhovsky, A. Slamova, M.
Schejbalova and P. Soucek, Pancreas, 2011, 40, 72-78.
114. I. K. Ilonen, J. V. Rasanen, E. I. Sihvo, A. Knuuttila, K. M.
Salmenkivi, M. O. Ahotupa, V. L. Kinnula and J. A. Salo, Acta
Oncol., 2009, 48, 1054-1061.
115. I. Iavicoli, V. Leso, L. Fontana and A. Bergamaschi, Eur. Rev.
Med. Pharmacol. Sci., 2011, 15, 481-508.
116. C. M. Mansfield, M. M. Alloy, J. Hamilton, G. F. Verbeck, K.
Newton, S. J. Klaine and A. P. Roberts, Chemosphere, 2015, 120,
206-210.

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CrystEngComm Accepted Manuscript

We highlight the crystal shape engineering of anatase TiO2 from thermodynamics, kinetics
and bio-inspired perspectives and its success in biomedical applications.