Access to this full-text is provided by Royal Society of Chemistry.
Content available from Chemical Science
This content is subject to copyright. Terms and conditions apply.
Structure-regulated enhanced Raman scattering
on a semiconductor to study temperature-
influenced enantioselective identification†
Jing Xu,
ab
Junhan Li,
a
Xuao Liu,
a
Xu Hu,
a
Hairihan Zhou,
a
Zhida Gao,
a
Jingwen Xu*
a
and Yan-Yan Song *
a
Surface-enhanced Raman scattering (SERS) spectroscopy is an effective technique that can reveal
molecular structure and molecular interaction details. Semiconductor-based SERS platforms exhibit
multifaceted tunability and unique selectivity to target molecules as well as high spectral reproducibility.
However, the detection sensitivity of semiconductors is impeded by inferior SERS enhancement. Herein,
a surface and interference co-enhanced Raman scattering (SICERS) platform based on corrugated TiO
2
nanotube arrays (c-TiO
2
NTs) was developed, and the coupling of structural regulation and photo-
induced charge transfer (PICT) effectively optimized the SERS performance of the semiconductor
substrate. Due to the regularly oscillating optical properties of the c-TiO
2
NTs, well-defined interference
patterns were generated and the local electric field was significantly increased, which greatly promoted
both the electromagnetic mechanism and PICT processes. The c-TiO
2
NTs were subsequently applied as
a highly sensitive SICERS substrate to investigate the mechanism of temperature influence on
enantioselective identification. This identification process is related to the existence of temperature-
sensitive hydrogen bonds and p–pinteraction. This work demonstrates a simply prepared, low-cost, and
sensitive SERS substrate that enables better investigation into molecular identification.
Introduction
Surface-enhanced Raman scattering (SERS) is a powerful tech-
nique for trace analysis. SERS offers insights into the chemical
structure and composition of molecules, enabling a wide range
of potential applications across various elds ranging from
nanostructure characterization to biochemical analysis.
1–3
Conventional SERS substrates are based on the electromagnetic
mechanism (EM),
4
which utilizes the localized surface plasmon
resonance (LSPR) effect of incident light excitation on a rough-
surfaced metal to locally amplify an electromagnetic eld.
5,6
Typical EM strategies involve the construction of noble metal
nanostructures with small gaps to generate “hotspots”and
enhance the Raman scattering of nearby molecules. However,
the signals of traditional EM-based SERS substrates signi-
cantly uctuate due to the inherently non-uniform distribution
of hotspots in the plasmonic nanostructures, and the poor
selectivity of these substrates for target molecules usually
results in complicated signal outputs. Another SERS mecha-
nism is the chemical mechanism, which is derived from the
efficient photo-induced charge transfer (PICT) that occurs
between a substrate and molecules. PICT amplies both the
molecular polarizability tensor and Raman scattering cross-
section.
7,8
To date, the cost-effective fabrication, high spectral
stability, and repeatability of semiconductors enable them
competitive SERS substrates. Unfortunately, owing to their
short-range charge transfer (CT) processes, the sensitivity of
semiconductor-based SERS substrates is still much lower than
that of noble metal-based SERS substrates.
Many strategies have been developed to enhance the
performance of semiconductor-based SERS substrates.
9
Among
them, defect engineering is a well-established solution that can
effectively activate the innate SERS activity of semiconductor-
based substrates. Generally, defect engineering alters the
band structure, surface properties, and densities of state of
semiconductors. This is achieved by using complicated
synthesis routes or post-treatment steps to introduce surface
defects, which endow semiconductors with enhanced CT effi-
ciency.
10
Moreover, the structure of semiconductors is a crucial
a
Department of Chemistry, College of Sciences, Northeastern University, Shenyang
110819, China. E-mail: yysong@mail.neu.edu.cn; xujingwen@mail.neu.edu.cn
b
State Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of the Ministry
of Education, College of Chemistry & Materials Science, Hebei University, Baoding
071002, China
†Electronic supplementary information (ESI) available: The interferometric
reectance spectra, Raman spectra, and SEM images of TiO
2
NTs; Raman
measurement of R6G and MB on TiO
2
membrane, s-TiO
2
NTs, and c-TiO
2
NTs;
schematic illustrations of preparation of chiral SICERS substrate; SERS spectra
for sensing L/D-DOPA under different chiral recognition time, Fe
3+
concentration, and Fe
3+
chelation time; Interferometric reectance spectra, XPS
survey spectra, EDS mapping images, FTIR spectra, zeta potential, and CD
spectra of different substrate. See DOI: https://doi.org/10.1039/d4sc00855c
Cite this: Chem. Sci.,2024,15,7308
All publication charges for this article
have been paid for by the Royal Society
of Chemistry
Received 5th February 2024
Accepted 17th April 2024
DOI: 10.1039/d4sc00855c
rsc.li/chemical-science
7308 |Chem. Sci.,2024,15,7308–7315 © 2024 The Author(s). Published by the Royal Society of Chemistry
Chemical
Science
EDGE ARTICLE
factor in enhancing the Raman signal. For example, multiple
reection processes in SERS substrates can lead to light inter-
ference, generating interference-enhanced Raman scattering
(IERS). By altering the nanostructure, the optical properties of
semiconductors such as light reection, absorption, and inter-
ference can be regulated, which affects the electromagnetic
eld.
11,12
Enhanced light absorption and LSPR at the nano-
structure of semiconductors produce an enhanced interaction
between different light routes and matter at optical hotspots,
where the localized electromagnetic eld is maximized. To date,
few efforts have been made to integrate nanostructure-designed
strategies and PICT processes to broaden the application
prospects of semiconductor-based SERS substrates.
TiO
2
nanostructures are typical semiconductor nano-
materials that show advantages in terms of stability, economy,
and biocompatibility. Among the various forms of TiO
2
, TiO
2
nanotube arrays (TiO
2
NTs) fabricated via electrochemical
anodization have a regular geometric morphology, making
them excellent candidates for use as SERS substrates.
13–16
However, typical TiO
2
NTs show poor SERS activity and are
merely used as uniform substrates for plasmonic metal.
17
In our
previous work, we found that tailoring the water content of the
electrolyte enabled the formation of TiO
2
NTs with a corrugated
surface capable of generating an interference signal.
18
The
interference of light is related to multiple reection processes at
material interfaces,
19,20
and IERS effects lead to the generation
of amplied Raman signals.
21–23
Herein, by combining chemical
enhancement and nanostructure regulation strategies,
a substrate containing corrugated TiO
2
NTs (c-TiO
2
NTs) with
optical interference properties was fabricated by a simple
preparation process for use as a surface and interference co-
enhanced Raman scattering (SICERS) platform with enhanced
sensitivity and high molecular selectivity (Fig. 1). By regulating
the nanostructure of the TiO
2
NTs, a concentrated electric eld
region was generated within hotspots, which facilitated both
the EM effect and the PICT efficiencies of the semiconductor-
based SERS substrate. The ultrasensitive and selective c-TiO
2
NTs substrate was subsequently employed to investigate the
inuence of temperature on enantioselective identication, and
the mechanism of this process was claried. Prussian blue (PB),
which had an amplied and interference-free Raman signal,
was formed in situ on the chiral c-TiO
2
NTs substrate. This
enabled the quantitative analysis of 3,4-dihydroxyphenylalanine
(L/D-DOPA) enantiomers. The enantioselective identication
mechanism was ascertained by investigating the temperature-
sensitive hydrogen bonds and p–pinteractions between the
chiral environment and DOPA isomers.
Results and discussion
Fabrication and characterization of SICERS substrate
c-TiO
2
NTs with good optical interference properties were
prepared via electrochemical anodization. During the nanotube
formation process, the oscillating optical properties of the
nanotubes were determined by the anodic oxidation conditions.
The water content of the electrolyte affected the growth rate and
etching rate of the nanotubes (i.e., the chemical dissolution
rate).
24
Bis(tetrabutylammonium) dihydrogen bis(isothiocya-
nate) bis(2,20-bipyridyl-4,40-dicarboxylate) ruthenium(II) (N719)
molecules were selected as Raman probes to optimize the
interference pattern of the TiO
2
NTs. The strongest SERS signal,
corresponding to the optimal interference conditions, was
generated on the c-TiO
2
NTs with a length of 1.73 mm (Fig. S1–
S3†). According to our previous work, corrugated nanotube
sidewalls are conducive to generating optical interference, and
the nanotube sidewall morphology can be regulated by
controlling the electrolyte water content.
18
Fig. S4 and S5†show
that the TiO
2
NTs grown in an electrolyte with low water content
had smooth tube walls, while the walls of the TiO
2
NTs grown in
an electrolyte with high water content had corrugated tube
Fig. 1 (A) Schematic illustration of the fabrication of c-TiO
2
NTs SICERS substrate. (B) SICERS mechanism of the c-TiO
2
NTs with significant
signal enhancement.
© 2024 The Author(s). Published by the Royal Society of Chemistry Chem. Sci.,2024,15,7308–7315 | 7309
Edge Article Chemical Science
walls. However, excess water in the electrolyte accelerated the
etching speed of the uorine-rich layer between the nanotubes,
leading to deformed nanotubes with a spongy appearance.
Thus, the optimum water content of the electrolyte was 15%
(Fig. S6†).
SICERS properties and mechanism of c-TiO
2
NTs
To gain the optimal Raman signal, the visible excitation wave-
length dependence phenomena was investigated based on the
Raman spectra of N719 under 532, 638, and 785 nm excitations
(Fig. S7†). Under the 532 nm laser excitation, N719 exhibited the
highest Raman signal intensity at the self-assembled mono-
layers level. Therefore, the 532 nm laser was used the excitation
light in the following study. The SICERS properties of the c-TiO
2
NTs and the effect of the TiO
2
NTs tube wall morphology on the
SERS signal were evaluated using a TiO
2
nanoparticle-based
membrane and TiO
2
NTs with smooth tube walls (s-TiO
2
NTs)
as the control (Fig. S8†). The SEM characterizations in Fig. 2A–D
show that the c-TiO
2
NTs were composed of parallel and
compact nanotubes with tube diameters of ∼155 nm.
Numerous corrugations were observed on the tube walls of the
c-TiO
2
NTs, providing an optical interference phenomenon.
Compared with the TiO
2
nanoparticle-based membrane, the s-
TiO
2
NTs and c-TiO
2
NTs showed stronger SERS signals aer the
adsorption of various probe molecules, including N719, 4-
aminothiophene (4-ATP), crystal violet (CV), PB, rhodamine 6G
(R6G), and methylene blue (MB) (Fig. 2E–H and S9†). The
periodically ordered nanotubular structures of the s-TiO
2
NTs
and c-TiO
2
NTs acted as photonic lattices to reect light at
specic frequencies, leading to enhanced Raman signals.
Moreover, the periodically ordered nanostructures of the TiO
2
NTs also provided uniform SERS signals, and the Raman
spectra collected from 30 random points on a single sample
showed a relative standard deviation (RSD) of 3.89% (Fig. 2I and
S10A†). Meanwhile, the facile preparation of TiO
2
NTs achieved
a high reproducibility of 2.45% across ten different c-TiO
2
NTs
samples (Fig. 2J and S10B†). Interestingly, the SERS signals of
most of the probe molecules were signicantly enhanced by the
c-TiO
2
NTs substrate compared with the s-TiO
2
NTs substrate.
However, 4-ATP only showed a slight Raman enhancement on
the c-TiO
2
NTs substrate (Fig. 2K). A comparison of the Raman
intensities of the N719 and 4-ATP peaks is shown in Fig. 2L. The
non-symmetric mode of N719 at 1266 cm
−1
(n(C]N) (bpy) +
n(C–C) intern-ring (bpy) vibration mode) was signicantly
inuenced by the CT process. The Raman shiof N719 at
1022 cm
−1
was attributed to the symmetric vibration of the
benzene ring, which was related to the LSPR contribution and
was independent of the CT effect. Compared with the s-TiO
2
NTs substrate, these N719 Raman peaks were signicantly
enhanced by the c-TiO
2
NTs substrate. However, for 4-ATP, only
a slight Raman enhancement was observed for the EM-affected
peak at 1087 cm
−1
, while the CT inuenced peak at 1593 cm
−1
showed a negligible change in intensity. Based on the peak
intensity of N719 at 1474 cm
−1
on a silicon wafer and c-TiO
2
NTs
(Fig. S11†), the enhancement factors (EFs) of c-TiO
2
NTs were
estimated to be 6.1 ×10
4
. Although the EFs of c-TiO
2
NTs were
lower than some two-dimensional semiconducting materials
Fig. 2 SEM images of (A and B) top view and (C and D) side view of c-TiO
2
NTs prepared using an electrolyte with 15% water content. Raman
measurement of (E) N719, (F) 4-ATP, (G) CV, and (H) PB on TiO
2
membrane, s-TiO
2
NTs, and c-TiO
2
NTs. (I) Signal intensity of N719 at 1474 cm
−1
collected from thirty random points on c-TiO
2
NT-based substrates to demonstrate uniformity. (J) Signal intensity of N719 at 1474 cm
−1
collected on ten different c-TiO
2
NTs samples to demonstrate reproducibility. (K) Raman intensity ratios of N719, R6G, CV, MB, 4-ATP, and PB on
the surfaces of the s-TiO
2
NTs and c-TiO
2
NTs to the TiO
2
membrane. (L) Raman intensity ratios of N719 (at 1022 cm
−1
and 1266 cm
−1
) and 4-
ATP (at 1087 cm
−1
and 1593 cm
−1
) on the surface of the s-TiO
2
NTs and c-TiO
2
NTs to the TiO
2
membrane.
7310 |Chem. Sci.,2024,15,7308–7315 © 2024 The Author(s). Published by the Royal Society of Chemistry
Chemical Science Edge Article
like MXenes and graphitic carbon, c-TiO
2
NTs exhibited high-
lights as good reproducibility, stability, and tailorability.
To investigate the enhanced SERS performance of the c-TiO
2
NTs compared to the s-TiO
2
NTs, the penetration process of the
incident laser on the substrates was evaluated. According to the
SERS mechanism, in Fig. 3A the collective excitation of electron
gas or surface plasma of the conductor (in this case, the Ti
substrate) was conned near the Ti/c-TiO
2
NTs interface, and
the light at the interface was signicantly amplied under
surface plasma excitation. As a result, both the incident radia-
tion and reected radiation at the Ti/c-TiO
2
NTs interface were
enhanced. According to the IERS mechanism, both the surface-
enhanced reected radiation and incident radiation contrib-
uted to the overall Raman scattering process in the IERS system,
leading to a signicant enhancement in SERS signal intensity.
The nite difference time domain (FDTD) results in Fig. 3B and
C show that the locally enhanced electric eld of the c-TiO
2
NTs
presented a periodic distribution along the nanotubes (in the z-
direction), and the eld strength was signicantly higher than
that of the s-TiO
2
NTs. Compared to the s-TiO
2
NTs, stronger
electromagnetic oscillation coupling between nanotubes was
achieved in the c-TiO
2
NTs, which enerated more hotspots in
the substrate. Meanwhile, due to the periodic arrangement of
the c-TiO
2
NTs nanostructure, multiple light scattering between
nanotube voids improved the light–matter interaction and
increased the probability of Raman scattering.
25,26
Therefore,
a concentrated electric eld region was formed within the c-
TiO
2
NTs nanostructure due to scattering and interference
effects, which was also crucial for its light-harvesting properties.
The enhanced SERS performance of the c-TiO
2
NTs for
different molecules was further evaluated. The direct band gap
(E
g
) of c-TiO
2
NTs was determined to be ∼3.50 eV by Tauc plots
analysis based on the UV-vis absorption spectrum (Fig. S12†).
Both the non-symmetric bond and symmetric bands of N719
were signicantly enhanced by the c-TiO
2
NTs compared to the
s-TiO
2
NTs. As shown in Fig. 3D, under 532 nm (2.3 eV) light
excitation, electrons were potentially transferred via two routes:
(1) from the highest occupied molecular orbital (HOMO) of the
prototype molecule N719 (−5.34 eV) to the conduction band
(CB, −3.45 eV) of the c-TiO
2
NTs; 2) from the HOMO to the
lowest unoccupied molecular orbital (LUMO, −3.10 eV) of N719.
In this case, the enhanced electric elds between the nanotubes
in the c-TiO
2
NTs substrate improved both the EM-based
Raman scattering and facilitated effective PICT processes in
the N719/c-TiO
2
NTs system. Consequently, this system exhibits
a signicantly enhanced CT-based Raman signal compared to
the N719/s-TiO
2
NTs system. In contrast, the 4-ATP/TiO
2
systems had unmatched band levels. Therefore, the CT process
did not occur, and the c-TiO
2
NTs only showed insignicant
Raman enhancement compared to the s-TiO
2
NTs (Fig. 3E). The
other probe molecules that had matched energy levels with the
c-TiO
2
NTs also exhibited distinct enhanced SERS signals on the
c-TiO
2
NTs when compared to the s-TiO
2
NTs (Fig. S13†). These
results conrmed the vital impact of the hotspots generated by
electromagnetic oscillation coupling between nanotubes in
PICT processes.
Construction of SICERS substrate for temperature-inuenced
enantioselective identication
Identifying enantiomers and elucidating the recognition
mechanism of an enantiomer identication strategy are
signicant challenges in bioanalysis because enantiomers have
identical molecular formulas and chemical properties.
27–29
Herein, the simple fabrication of c-TiO
2
NTs SICERS substrates
with high stability and reproducibility motivated us to develop
a platform for investigating the mechanism of enantioselective
identication. A chiral environment based on the c-TiO
2
NTs
was constructed to explore the effect of temperature on enan-
tiomer (L/D-DOPA) identication (Fig. 4A and S14†). The char-
acterization of this analysis platform (Fig. S15–S21†)
demonstrated that the prepared L/D-Phe/O-Phos/c-TiO
2
NTs
SICERS substrates were constructed successfully with homo-
chirality. Fig. S22†shows the construction of the chiral recog-
nition signal amplication sensing platform. Aer L/D-DOPA
identication, an Fe
3+
–DOPA complex was formed in situ
through chelation between Fe
3+
and the phenol hydroxyl group
of DOPA.
15
Fe
3+
subsequently reacted with [Fe(CN)
6
]
4–
to form
PB nanocrystals. The selective recognition of DOPA enantio-
mers on the chiral SICERS substrate was determined by
comparing the peak intensity of PB at 2158 cm
−1
. Considering
that the DOPA molecules tend to self-polymerize in a basic
solution,
30,31
an acidic environment was thus chosen to ensure
the DOPA monomer to be recognized on the substrate. To
obtain the apparent recognition results, the reaction conditions
were optimized as follows: the chiral recognition time was
Fig. 3 (A) Schematic diagram illustrating the SICERS effect of the c-
TiO
2
NTs and generation of Raman signal. Electromagnetic field
enhancement images showing vertical sections of (B) s-TiO
2
NTs and
(C) c-TiO
2
NTs. Energy level diagram and CT pathway of (D) N719 and
(E) 4-ATP adsorbed on c-TiO
2
NTs.
© 2024 The Author(s). Published by the Royal Society of Chemistry Chem. Sci.,2024,15,7308–7315 | 7311
Edge Article Chemical Science
60 min, the Fe
3+
concentration was 0.5 mM, and the Fe
3+
chelation time was 30 min (Fig. S23–S25†). To determine the
inuence of electrostatically adsorbed Fe
3+
ions on DOPA
sensing, we also explored the PB generation ability induced by
the adsorbed Fe
3+
ions on c-TiO
2
NTs, O-Phos/c-TiO
2
NTs, and L-
Phe/O-Phos/c-TiO
2
NTs (Fig. S26†). Apparently, very weak PB
signals were detected on these samples, indicative the effective
PB-growth strategy by using the recognized L/D-DOPA.
Previous studies have shown that the hydrogen bonds
between the L/D-Phe and L/D-DOPA is crucial for the chiral
recognition process, and the strength of this hydrogen bond is
closely related to temperature.
32
As predicted, chiral substrates
exhibited different chiral recognition phenomena at different
recognition temperatures (Fig. 4B–D). The PB Raman signal
intensities obtained for the same concentrations of L/D-DOPA on
the L-Phe/O-Phos/c-TiO
2
NTs substrate at 5 °C signicantly
overlapped, suggesting that the target enantiomer was not able
to be distinguished using the homochiral substrate at a low
temperature. At 25 °C, the PB Raman intensity generated aer D-
DOPA identication by the L-Phe/O-Phos/c-TiO
2
NTs substrate
was higher than that of L-DOPA. For the D-Phe/O-Phos/c-TiO
2
NTs substrate (Fig. 4E–G), the PB Raman intensities aer
recognizing L-DOPA at both 5 °C and 25 °C were signicantly
higher than that of D-DOPA. To understand the chiral recogni-
tion behavior of the substrates under different temperatures,
chiral recognition based on L-Phe and D-Phe was examined at
a range of temperatures from 0 to 45 °C (Fig. 4D and G). The
results indicated that chiral selectivity for the DOPA enantiomer
depended on the experimental temperature. The selectivity of
the L-Phe/O-Phos/c-TiO
2
NTs chiral sensor for D-DOPA increased
with increasing temperature, and this chiral sensor exhibited
the highest selectivity for D-DOPA, especially at 25 °C. Mean-
while, the D-Phe/O-Phos/c-TiO
2
NTs chiral sensor showed high
selectivity at both 5 °C and 25 °C. For other chiral molecules
Fig. 4 (A) Schematic illustrations showing the recognition of DOPA enantiomers by the L-Phe/O-Phos/c-TiO
2
NTs and D-Phe/O-Phos/c-TiO
2
NTs substrates at 5 °C and 25 °C. Raman spectra of PB after L/D-DOPA recognition by L-Phe/O-Phos/c-TiO
2
NTs substrate at (B) 5 °C and (C) 25 °
C. (D) Influence of temperature on the recognition of L/D-DOPA by the L-Phe/O-Phos/c-TiO
2
NTs substrate. Raman spectra of PB after L/D-
DOPA recognition by D-Phe/O-Phos/c-TiO
2
NTs substrate at (E) 5 °C and (F) 25 °C. (G) Influence of temperature on the recognition of L/D-DOPA
by the D-Phe/O-Phos/c-TiO
2
NTs substrate. Energy-minimized dominant interaction models (ball-and-stick) of (H) L-Phe with D-DOPA, (I) L-Phe
with L-DOPA, (J) D-Phe with L-DOPA, and (K) D-Phe with D-DOPA.
7312 |Chem. Sci.,2024,15,7308–7315 © 2024 The Author(s). Published by the Royal Society of Chemistry
Chemical Science Edge Article
containing phenolic hydroxyl groups (such as L/D-adrenaline),
the temperature also affected the chiral recognition process
(Fig. S27†).
The interactions between the L/D-Phe and DOPA enantiomers
were then investigated, as schematically shown in Fig. 4H–K.
Both DOPA enantiomers interacted with L/D-Phe and formed
hydrogen bonds. For L-Phe/O-Phos/c-TiO
2
NTs, the interaction
between D-DOPA and L-Phe involved the formation of two
hydrogen bonds, while the interaction between L-DOPA and L-
Phe formed one hydrogen bond. While for D-Phe/O-Phos/c-TiO
2
NTs, L-DOPA bonded to D-Phe through three hydrogen bonds
and p–pinteraction, and D-Phe bonded to D-DOPA via only one
hydrogen bond. Therefore, the temperature-inuenced chiral
recognition process was essentially decided by the different
binding modes between the L/D-Phe and DOPA enantiomers.
Low temperatures are favorable for p–pinteraction, but
molecular motion is limited at low temperatures. However,
hydrogen bonds are signicantly inhibited due to the limited
molecular motion at low temperatures.
33,34
Thus, with
increasing temperature, the hydrogen bonds became more
prominent, which enhanced the D-DOPA selectivity on the L-
Phe/O-Phos/c-TiO
2
NTs substrate (Fig. 4D). The D-Phe/O-Phos/c-
TiO
2
NTs substrate exhibited higher selectivity for L-DOPA at low
temperatures, especially at 5 °C (Fig. 4G). This was attributed to
the stable p–pinteractions between D-Phe and L-DOPA at low
temperatures. Molecular motion accelerates with increasing
temperature due to the weakened intramolecular interactions.
Thus, at 25 °C, the formation of hydrogen bonds between D-Phe
and L-DOPA was enhanced. However, excessively high temper-
atures (30–45 °C) broke the stable hydrogen bonds between the
L/D-Phe and DOPA enantiomers, resulting in a subsequent
decline in recognition efficiency.
The quantitative analysis capability of L-Phe/O-Phos/c-TiO
2
NTs was investigated (Fig. S28†). The PB Raman signal recorded
on the SICERS platform exhibited good linear relationships in
the L/D-DOPA concentration ranging from 10
−10
to 10
−5
M with
the limit of detection (LOD, dened as the mean of blank +3s,s
is the standard deviation of blank) of 1.3×10
−11
M for L-DOPA
and 1.0 ×10
−11
M for D-DOPA. The X-ray diffraction (XRD)
patterns and SEM images also provided the solid evidence for
the of PB formation on the surface of c-TiO
2
NTs by the DOPA
enantiomer recognition process (Fig. S29 and S30†). In addi-
tion, the selectivity of the SICERS platform was further evalu-
ated by discriminating other enantiomers, including L/D-
tryptophan (L/D-Trp), L/D-carnitine, L/D-tyrosine (L/D-Tyr), L/D-
glutamic acid (L/D-Glu), and L/D-cysteine (L/D-Cys) (Fig. S31†).
Owing to no phenolic hydroxyl groups in the structures of these
enantiomers, Fe
3+
ions cannot be trapped, and thus no obvious
PB signal was recorded. The above results conrm the excellent
quantitative ability of the as-proposed SICERS platform for
DOPA enantiomers.
Experimental
Preparation of TiO
2
NTs
Ti foils (15 mm ×15 mm ×0.1 mm) were sequentially cleaned
by ultrasonication in isopropanol, ethanol, and deionized
water, then dried under a ow of N
2
. The c-TiO
2
NTs with optical
interference properties were fabricated by electrochemical
anodization.
18,24
Briey, each Ti foil was anodized at 60 V for
40 min in an electrolyte containing 0.5 wt% NH
4
F and varying
water content to prepare the c-TiO
2
NTs.
Preparation of L/D-Phe/O-Phos/c-TiO
2
NTs
The as-formed c-TiO
2
NTs were rst functionalized with O-Phos
by immersion in a 10 mM O-Phos aqueous solution at 4 °C for
12 h. Subsequently, chiral recognition molecules (L/D-Phe) were
introduced onto the prepared O-Phos/c-TiO
2
NTs using a classic
N-(3-dimethylaminopropyl)-nethylcarbodiimide hydrochloride
(EDC)/N-hydroxysulfosuccinimide (NHS) coupling reaction. To
link L/D-Phe onto the O-Phos/c-TiO
2
NTs, 1 mM L/D-Phe was
dissolved in deionized water containing 10 mg mL
−1
EDC and
5mgmL
−1
NHS. This mixture was reacted for 30 min to activate
the carboxyl group of L/D-Phe. The O-Phos/c-TiO
2
NTs were
soaked in this solution for 12 h at room temperature to obtain
the L/D-Phe/O-Phos/c-TiO
2
NTs.
Temperature induced chiral recognition for L/D-DOPA
Firstly, the as-prepared L/D-Phe/O-Phos/c-TiO
2
NTs were
immersed in L/D-DOPA (pH 5.5) aqueous solution at different
temperatures for 60 min. Aer immersion, the substrates were
cleaned with deionized water three times to remove uncom-
bined L/D-DOPA molecules. The cleaned samples were then
incubated in 0.5 mM FeCl
3
aqueous solution for 30 min to x
Fe
3+
. Subsequently, PB was formed by immersing the samples
in a 0.5 mM K
4
[Fe(CN)
6
] aqueous solution at room temperature
for 30 min.
Raman measurement
The c-TiO
2
NTs were immersed in a 1 mM ethanol solution
containing N719 and reacted at 70 °C for 12 h. Raman spectra
were recorded using a 532 nm laser (10% power) equipped with
a50×long-distance objective and a spot size of 1 mm. The data
acquisition time was 10 s, the confocal hole size was 500 mm,
and the slit aperture size was 200 mm. The spectrometer was
calibrated using the Raman signal from a silicon wafer at
520.7 cm
−1
. For each measurement, Raman spectra were
collected from ve different locations to determine the average
signal strength.
Calculation of the electromagnetic surface enhancement in
TiO
2
NTs geometries
The eld intensity distribution of the c-TiO
2
NTs and s-TiO
2
NTs
was calculated by FDTD. The experimental parameters for the
calculations were obtained from the SEM images of the c-TiO
2
NTs and s-TiO
2
NTs. In the FDTD simulations, four TiO
2
NTs
were used as the model, 0.3 nm was used as a unit, and
a 532 nm laser was used to irradiate the model along the zand y
axes.
© 2024 The Author(s). Published by the Royal Society of Chemistry Chem. Sci.,2024,15,7308–7315 | 7313
Edge Article Chemical Science
Conclusions
In summary, a c-TiO
2
NTs substrate with a facilely tailorable
nanostructure was proposed in this work as a SICERS platform
due to its enhanced Raman scattering properties. This platform
was employed to investigate the inuence of temperature on
enantioselective identication and the mechanism of this
inuence. By regulating the TiO
2
NTs nanostructure, an
enhanced electric eld with interference properties was gener-
ated in the c-TiO
2
NTs, facilitating both the EM and PICT
processes in the semiconductor-based SERS substrate. A signal
amplication strategy involving the in situ formation of PB was
employed to determine that temperature-sensitive hydrogen
bonds and p–pinteractions between the chiral environment of
the substrate and isomers were the key to enantioselective
recognition. This work offers new opportunities for improving
the sensitivity of semiconductor-based SERS substrates with
simple methods and is expected to be helpful for biochemical
analysis, catalyst monitoring, and material determination.
Data availability
All the data supporting this article have been included in the
main text and the ESI.†
Author contributions
Y.-Y. Song and J. W. Xu conceived the concept and directed the
project. J. Xu performed experiments, analyzed data, and wrote
the manuscript. J. H. Li, X. Hu, H. R. H. Zhou performed the
experiments. X. A. Liu carried out the theoretical study. Z. D.
Gao collected and analyzed the data. All the authors discussed
the results and assisted during the manuscript preparation.
Conflicts of interest
There are no conicts to declare.
Acknowledgements
This work was supported by the National Natural Science
Foundation of China (No. 22074013, 22374015, and 22204016)
and Liaoning Provincial Natural Science Foundation
(LJKQZ2021001). Special thanks are due to the instrumental or
data analysis from Analytical and Testing Center, Northeastern
University.
Notes and references
1 C. Zong, M. X. Xu, L. J. Xu, T. Wei, X. Ma, X. S. Zheng, R. Hu
and B. Ren, Chem. Rev., 2018, 118, 4946–4980.
2 M. F. Cardinal, E. V. Ende, R. A. Hackler, M. O. McAnally,
P. C. Stair, G. C. Schatz and R. P. Van Duyne, Chem. Soc.
Rev., 2017, 46, 3886–3903.
3 G. Song, W. B. Gong, S. Cong and Z. G. Zhao, Angew. Chem.,
Int. Ed., 2021, 60, 5505–5511.
4 S. Y. Ding, E. M. You, Z. Q. Tian and M. Moskovits, Chem.
Soc. Rev., 2017, 46, 4042–4076.
5 L. A. Lane, X. M. Qian and S. M. Nie, Chem. Rev., 2015, 115,
10489–10529.
6 Q. Zhao, H. Hilal, J. Kim, W. Park, M. Haddadnezhad, J. Lee,
W. Park, J. W. Lee, S. Lee, I. Jung and S. Park, J. Am. Chem.
Soc., 2022, 144, 13285–13293.
7 S. Cong, X. H. Liu, Y. X. Jiang, W. Zhang and Z. G. Zhao, Int. J.
Innov., 2020, 1, 100051.
8 X. T. Wang and L. Guo, Angew. Chem., Int. Ed., 2020, 59,
4231–4239.
9 G. Song, S. Cong and Z. G. Zhao, Chem. Sci., 2022, 13, 1210–
1224.
10 J. Lin, Y. Shang, X. X. Li, J. Yu, X. T. Wang and L. Guo, Adv.
Mater., 2017, 29, 1604797.
11 X. L. Zhu, C. Vannahme, E. H. Nielsen, N. A. Mortensen and
A. Kristensen, Nat. Nanotechnol., 2016, 11, 325–329.
12 T. Kim, J. Lee, E. S. Yu, S. Lee, H. Woo, J. Kwak, S. Chung,
I. Choi and Y. S. Ryu, Small, 2023, 19, 2207003.
13 J. W. Xu, C. C. Liang, Z. D. Gao and Y. Y. Song, Chin. Chem.
Lett., 2023, 34, 107863.
14 J. L. Guo, X. A. Liu, J. J. Zhao, H. J. Xu, Z. D. Gao, Z.-Q. Wu
and Y.-Y. Song, Chem. Sci., 2023, 14, 1742–1751.
15 J. Xu, Y. F. Xue, X. X. Jian, Y. Zhao, Z. Q. Dai, J. W. Xu,
Z. D. Gao, Y. Mei and Y. Y. Song, Chem. Sci., 2022, 13,
6550–6557.
16 L. L. Yang, J. J. Feng, J. N. Wang, Z. D. Gao, J. W. Xu, Y. Mei
and Y. Y. Song, Chin. Chem. Lett., 2022, 33, 5169–5173.
17 L. L. Yang, C. X. Zhao, J. W. Xu, J. L. Guo, Z. D. Gao and
Y. Y. Song, Chem. Commun., 2020, 56, 10333–10336.
18 Y. Y. Song and P. Schmuki, Electrochem. Commun., 2010, 12,
579–582.
19 G. A. N. Connell, R. J. Nemanich and C. C. Tsai, Appl. Phys.
Lett., 1980, 36,31–33.
20 R. J. Nemanich, C. C. Tsai and G. A. N. Connell, Phys. Rev.
Lett., 1980, 44, 273–276.
21 X. Ling and J. Zhang, J. Phys. Chem. C, 2011, 115, 2835–2840.
22 L. B. Gao, W. C. Ren, B. L. Liu, R. Saito, Z. S. Wu, S. S. Li,
C. B. Jiang, F. Li and H. M. Cheng, ACS Nano, 2009, 3, 933–
939.
23 N. Jung, A. C. Crowther, N. Kim, P. Kim and L. Brus, ACS
Nano, 2010, 4, 7005–7013.
24 P. Roy, S. Berger and P. Schmuki, Angew. Chem., Int. Ed.,
2011, 50, 2904–2939.
25 J. D. Joannopoulos, P. R. Villeneuve and S. H. Fan, Nature,
1997, 386, 143–149.
26 C. T. Yip, H. T. Huang, L. M. Zhou, K. Y. Xie, Y. Wang,
T. H. Feng, J. S. Li and W. Y. Tam, Adv. Mater., 2011, 23,
5624–5628.
27 E. Hendry, T. Carpy, J. Johnston, M. Popland,
R. Mikhaylovskiy, A. J. Lapthorn, S. M. Kelly, L. D. Barron,
N. Gadegaard and M. Kadodwala, Nat. Nanotechnol., 2010,
5, 783–787.
28 K. Yao and Y. M. Liu, Nanoscale, 2018, 10, 8779–8786.
29 Y. R. Liu, Z. L. Wu, D. W. Armstrong, H. Wolosker and Y. B
Zheng, Nat. Rev. Chem, 2023, 7, 355–373.
7314 |Chem. Sci.,2024,15,7308–7315 © 2024 The Author(s). Published by the Royal Society of Chemistry
Chemical Science Edge Article
30 H. Lee, S. M. Dellatore, W. M. Miller and P. B. Messersmith,
Science, 2007, 318, 426–430.
31 J. Sed´
o, J. Saiz-Poseu, F. Busqu´
e and D. Ruiz-Molina, Adv.
Mater., 2013, 25, 653–701.
32 J. H. Zhao, H. Q. Wang, Y. H. Cai, J. J. Zhao, Z. D. Gao and
Y. Y. Song, ACS Sens., 2024, 9, DOI: 10.1021/
acssensors.4c00137.
33 S. Cong, Y. Y. Yuan, Z. G. Chen, J. Y. Hou, M. Yang, Y. L. Su,
Y. Y. Zhang, L. Li, Q. W. Li, F. X. Geng and Z. G. Zhao, Nat.
Commun., 2015, 6, 7800.
34 E. Feng, T. T. Zheng, X. X. He, J. Q. Chen, Q. Y. Gu, X. He,
F. H. Hu, J. H. Li and Y. Tian, Angew. Chem., Int. Ed., 2023,
62, e202309249.
© 2024 The Author(s). Published by the Royal Society of Chemistry Chem. Sci.,2024,15,7308–7315 | 7315
Edge Article Chemical Science
Available via license: CC BY 3.0
Content may be subject to copyright.
