Photocatalytic Synthesis of Pipecolic Acid from Lysine on TiO2: Effects of the Structure of Catalysts and Adsorbed Species on Chiral Selectivity

Article abstract of DOI:10.1021/acs.oprd.8b00299

A one-step photocatalytic synthesis of l-pipecolic acid (l-PCA) from l-lysine (l-Lys) has been investigated by in situ infrared (IR), circular dichroism, and ¹H NMR spectroscopy. Chiral selectivity toward l-Lys was found to be governed by the structure of adsorbed l-Lys and the structure of TiO₂. Both anatase and rutile were not able to catalyze the reaction in a solvent-free environment. In situ IR studies revealed that l-Lys adsorbed on these TiO₂ in a dicationic form of which the positive -NH₃⁺ functional groups are not able to interact with photogenerated holes. Interestingly, P-25 TiO₂, which contains 80 wt % anatase and 20 wt % rutile, adsorbs l-Lys in a zwitterionic form, allowing its hydrogen in the α-amino group to be abstracted by the photogenerated hole, producing racemic PCA. The addition of H₂O as a solvent allowed l-Lys to be adsorbed on P-25 in an anionic form, producing l-PCA as a major product. This study demonstrates that the reaction environment has a direct impact on the structure of adsorbed species that controls the selectivity of a chiral synthesis.

Full text of DOI:10.1021/acs.oprd.8b00299

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Full Paper
2
Photocatalytic Synthesis of Pipecolic Acid from Lysine on TiO: Effects
of the Structure of Catalysts and Adsorbed Species on Chiral Selectivity
Yuxin Zhai, and Steven S. C. Chuang
Org. Process Res. Dev., Just Accepted Manuscript • DOI: 10.1021/acs.oprd.8b00299 • Publication Date (Web): 26 Oct 2018
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Photocatalytic Synthesis of Pipecolic Acid from Lysine on TiO2: Effects
of the Structure of Catalysts and Adsorbed Species on Chiral Selectivity
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Yuxin Zhai1† and Steven S.C. Chuang1*
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1Department of Polymer Science, The University of Akron, Akron, Ohio 44325, USA.
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Table of Content
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For Table of Contents Only
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Solid-solid (S-S) photocatalytic reaction: α route
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+
NH3
UV
35 mW/cm2
HN
HO
H2N
O
O
O
NH2
Zwitterionic structure
Racemic pipecolic acid
H2N
Liquid-solid (L-S) photocatalytic reaction : ε route
O
OH
L-Lysine
NH2
UV
HN
H2N
46 mW/cm2
O
O
O
O
Anionic structure
L-Pipecolic acid
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Abstract
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A one-step photocatalytic synthesis of L-Pipecolic acid (L-PCA) from L-Lysine (L-Lys) has been
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investigated by in situ infrared (IR) spectroscopy, circular dichroism, and H NMR. Chiral
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selectivity toward L-Lys was found to be governed by the structure of adsorbed L-Lys and the
structure of TiO2. Both anatase and rutile were not able to catalyze the reaction in a solvent-free
environment. In situ infrared studies revealed that L-Lys adsorbed on these TiO2 in a di-cationic
+
form of which positive -NH3 functional group is not able to interact with photogenerated holes.
Interestingly, P-25 TiO2, which contain 80 wt% of anatase and 20 wt% of rutile, adsorbs L-Lys in
a zwitterionic form, allowing its hydrogen in the α-amino group to be abstracted by the
photogenerated hole, producing racemic PCA. The addition of H2O as a solvent allowed L-Lys to
be adsorbed on P-25 in an anionic form, producing L-PCA as a major product. This study
demonstrates that the reaction environment has a direct impact on the structure of adsorbed species
that controls the selectivity of a chiral synthesis.
Keywords
Photocatalysis, in situ infrared spectroscopy, chirality, amino acid, liquid-solid and solid-solid
synthesis
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Introduction
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Titania (TiO2) has been extensively studied in photocatalysis because of its chemical stability, long
durability, nontoxicity, and low cost.1-5 The core principle of photocatalysis is the use of photo-
generated electrons and holes on the surface of a photocatalyst to initiate redox reaction steps as
illustrated in Figure 1. Upon UV-irradiating on an oxide semiconductor, photo-generated electrons
(e-) in the conduction band and holes (h+) follow several pathways: (i) surface recombination, (ii)
recombination in the bulk, (iii) donation of surface e- to an electron acceptor (A) adsorbed on the
surface, and (iv) migration of h+ to the surface, accepting an electron from a donor species (D) on
the surface.3 The species A- and D+ can further react to yield products. Photogenerated electrons
in the conduction band may undergo a trapping process in which photogenerated electrons are
captured in localized states with shallow and “deep” traps.6-13
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A-
e-: photogenerated electrons
A: electron acceptors
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A
e-
(iii)
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Conduction band
e-
e- e- e-
e-
e-
UV
Shallow trap
0.12-0.3 eV
e-
+ (ii)
e-
h+
(i) +
h+
h+
h+ h+ h+
h+ h+
Valence band
h+
(iv)
D+
h+: photogenerated holes
D: electron donors
D
Figure 1. Photocatalytic pathways on TiO2: (i) surface recombination of e- and h+, (ii) bulk
recombination of e- and h+, (iii) donation of electrons to electron acceptors, and (iv) donation of
holes to electron donors.
Various forms of TiO2 and modified TiO2 (i.e., Cu2O/TiO2, Pt/TiO2, Au/CeO2/TiO2, and various
additives) have been studied for the removal of organics in aqueous media, treatments of
contaminants in air, water splitting, CO2 reduction, and synthesis of organics.14-33 Specifically,
additives such as Cu2O are able to enhance the activity and stability of TiO2.33 One promising
application of TiO2-photocatalysis is the production of high-value pharmaceutical precursors
involved with amino acids. L-Pipecolic acid (L-PCA) is a high-value amino acid, a key component
in immunosuppressant, the anticancer agent, and the HIV protease inhibitor. The one-step
photocatalytic synthesis of L-PCA from a low-cost L-Lysine (L-Lys), illustrated in Scheme 1,
provides a low-cost and green synthesis route with relatively high yields compared to the other
methods such as enzymatic reactions, stereoselective transformation, and chemical resolution
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organized in Table S1.34-41 This synthesis pathway proceeds through a number of reaction steps:
(i) abstraction of H from -NH2 by photogenerated hole (h+), (ii) hydrolysis of the imine to produce
an aldehyde, (iii) intramolecular condensation of the aldehyde with a remaining amino group to
form a cyclic Schiff base (CSB), and (iv) reduction of CSB into L-PCA by photogenerated
electrons.28-32 According to the pathways illustrated in Figure 1, the synthesis pathway involved
both the oxidation step with h+ and the reduction step with e-. L-Lys serves as an electron donor
in step (i); the intermediate species, CSB, serves as an electron acceptor.
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A number of studies have shown that chiral selectivity toward L-PCA in aqueous solution varies
with the type and morphology of photocatalysts.28-32 TiO2 photocatalysts produced L-excess PCA
with an optical purity of 47% while CdS gave racemic PCA.30-31 Modifying TiO2 with SiO2 shells
enhanced L-PCA selectivity.29 Depositing noble metals (i.e., Rh, Pt, Pd) on P-25 TiO2 controlled
the selectivity of the reduction step.28, 32 It has been suggested the location (α or ε) where the
amino acid is oxidized to an imine controls the chiral selectivity. Scheme 1 illustrates how this
oxidation and subsequent steps is initiated by photogenerated holes. Oxidation of an α-amino
group by photogenerated holes would result in the loss of optical purity while oxidation of ε-amino
groups would maintain the chirality.28, 31-32 L-Lys, containing primary amine and carboxylic
functional groups, could adsorb on the catalyst surface in various forms through these functional
groups.42-47
Scheme 1. Reaction pathway of L-Lys to L-PCA or racemic PCA
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α-route
racemic pipecolic acid
(racemic PCA)
L-Lysine (L-Lys, zwitterionic)
O
O
O
O
O
O
O
2e-
2H+
O
2h+
-NH3
O
-H2O
+H3N
+H3N
+H3N
+H2O
NH2 -2H+
NH
NH OH
N
OH
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ε-route
L-Pipecolic acid
(L-PCA, zwitterionic)
L-Lysine (L-Lys, anionic)
O
O
O
O
O
O
2e-
2H+
O
2h+
NH2 -2H+
-NH3
O
-H2O
+
NH2 O-
+H2O
H2N
NH2
NH2
HN
O
N
OH
Little is known the effect of the crystalline structure of TiO2 (i.e., anatase, rutile, and its mixed
states) and the reaction environment (i.e., adsorbed water and aqueous environment) on the
structure of adsorbed species could determine the reaction pathway (i.e., α or ε route). In this
study, we employed the in situ infrared (IR) spectroscopy to investigate the key factors determining
activity and chiral selectivity (i.e., reaction pathways) for the photocatalytic synthesis of L-PCA
from L-Lys in both solvent-free and aqueous solution environment. The in situ FTIR results
unraveled that the chiral selectivity of the synthesis is governed by the adsorbed structures of L-
Lys on TiO2.
Experimental
Materials
P-25 (Degussa, 56 m2/g), anatase (Sigma Aldrich, <25 nm, 99.7%, 45 – 55 m2/g), L-Lysine (L-
Lys, Sigma Aldrich, ≥98%), L-Pipecolic acid (L-PCA, Sigma Aldrich, 99%), racemic pipecolinic
acid (racemic PCA, Sigma Aldrich, 98%) were used as received.
Preparation of photocatalysts
P-25 TiO2 and anatase were pretreated in a furnace at 300 °C for 3 h to remove the pre-adsorbed
H2O and organics. Rutile was obtained from phase transformation of anatase at 800 °C for 5 h.
Solid-solid (S-S) photocatalytic reaction
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0.1g TiO2 (P-25, anatase, and rutile) was mixed with 0.05 g L-Lys and ball milled at room
temperature to obtain a homogenous mixture. The obtained mixture was loaded in a DRIFTs
(diffuse reflectance infrared Fourier transform spectroscopy) cell, shown in Figure 2 (a). The
sample was capped by a three-window dome to isolate from ambient. UV light emitted from a
350-Watt Hg lamp source (Newport 6286) with a lamp power supply (Thermo Oriel 69910) was
directed toward L-Lys/TiO2 through a CaF2 front window at 35 mW/cm2. The UV light intensity
was measured by a power meter (Newport, 1918-C), which was placed below a CaF2 window to
emulate the light received by the catalyst. The cell was placed and aligned in the beam path of in
an FTIR spectrometer (Nicolet 6700, Thermo Scientific). In situ FTIR studies were conducted
with the following steps: (i) pretreatment of the sample to 120 °C for 10 min, (ii) UV irradiation at
30 °C for 10 min, and (iii) UV off at 30 °C for 10 min. Samples were exposed to an Ar flow at a
flow rate of 100 cm3/min during these steps. The IR absorbance spectra of adsorbed species on
the catalyst were obtained by log(I0/I), where I is the IR single-beam intensity in the step (ii) and
I0 is the IR single-beam intensity of the pretreated sample after step (i). The IR single-beam
intensity is obtained by Fourier transform of an interferogram. The Kubelka-Munk function was
not used because of the uncertainty in collecting absorbance and Kubelka-Munk function with the
concentration of adsorbed species. Furthermore, the Kubelka-Munk function will diminish low-
intensity IR peak of adsorbed L-Lys.48
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Special attention was paid to the possibility of the effect of pretreatments and IR chamber
environment on the IR background spectra of TiO2. Examination of IR spectra of TiO2 and IR
chamber environment in Figure S1 showed that the IR background spectra of TiO2 particles were
not affected by the pretreatment.
Liquid-solid (L-S) photocatalytic reaction in an aqueous environment
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Figure 2 (b) and (c) illustrate the experimental setup of ex situ and in situ FTIR-ATR study of L-
S photocatalytic reaction of L-Lys/TiO2 solution. 0.5 g of TiO2, in the form of P-25, anatase, and
rutile, was dispersed in 50 g of 1 mmol/L L-Lys/D2O solution under stirring. In the ex situ
experiment, the resultant L-Lys/TiO2 solutions were placed in a bottle under stirring and irradiated
by UV with the light intensity of 46 mW/cm2 for 60 min in the presence of Ar flow at 150 cc/min.
A mass spectrometry (MS, Pfeiffer QMS 200) was connected to the gas outlet for examining NH3,
one of the byproducts. The formation of NH3 during photocatalysis could be found in the MS
intensity profile in Figure 2 (b). The amount of L-PCA and racemic PCA were determined by a
number of spectroscopic techniques while gaseous NH3 was not further quantified. In the in situ
FTIR-ATR experiment, the same L-Lys/P-25 solution was placed on a Ge crystal in an ATR cell
(VeeMAX III, Pike) and allowed P-25 to precipitate on the Ge surface for 1 h to achieve a steady
condition prior to UV irradiation, shown in Figure 2 (c), followed by a 20 min UV irradiation at
the light intensity of 46 mW/cm2.
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Characterization
The reactants and products from S-S and L-S photocatalytic reactions were collected and dissolved
or diluted in D2O. The samples in D2O were measured by electrospray ionization mass
spectrometry (ESI-MS, Waters Synapt HDMS quadrupole/time-of-flight (Q/ToF) mass
spectrometry (Waters, Milford, MA)), circular dichroism (CD, J-1500 spectropolarimeter, Jasco
1
Inc., Japan), H NMR (Varian NMRS 500), and UV-vis spectroscopic analysis (Hitachi U-3900
research grade UV–Vis spectrophotometer). CD determines the chirality of products by the
difference between the absorbance of left-handed (L-) and right-handed (D-) circular plane-
polarized light.49-50
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The standard samples were prepared by mixing TiO2 with L-Lys, racemic PCA, and L-PCA with
the weight ratio of TiO2 to amino acid as 2:1 and measured by FTIR. The standard L-Lys, racemic
PCA and L-PCA were dissolved in D2O and characterized by 1H NMR, CD, ESI-MS, and UV-vis.
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Figure 2. Experimental setup: (a) In situ solid-solid photocatalytic reaction of L-Lys/P-25 in
DRIFTs cell, (b) Ex situ liquid-solid photocatalytic reaction photocatalysis of L-Lys/P-25 solution
coupled with a mass spectrometry, and (c) In situ liquid-solid photocatalytic reaction of L-Lys/P-
25 solution on ATR cell.
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Results and Discussion
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Solid-solid photocatalytic reactions
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Figure 3 compares the IR spectra of L-Lys and L-Lys adsorbed on various types of TiO2. Adsorbed
L-Lys on TiO2 gives the N-H stretching of NH2 at 3361 cm-1 and 3286 cm-1, C-H stretching at
2927 cm-1, asymmetric stretching of COO- at 1612 cm-1 and symmetric stretching of COO- at 1411
cm-1.51-54 The band assignments for the specific modes of vibration in 1400 – 1700 cm-1 are listed
in Table 1 which follows the results of IR studies on protonated L-Lys.42, 47, 55-56 The protonated -
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+
NH2, i.e., -NH3 , in the L-Lys zwitterion gives a broad band in 2400 – 3200 cm-1, which is
overlapped with C-H stretching at 2927 cm-1. The broadness of this band reflects the extent of
+
+
hydrogen bonding between -NH3 and -COO-. -NH3 possesses two additional vibrational modes:
bending mode in 1610 – 1650 cm-1, which is overlapped with -COO-, and a combination mode of
asymmetric deformation and hindered rotation at 2113 cm-1.51-54 Further comparison of IR spectra
of adsorbed L-Lys on TiO2 in Figure 3 as well as IR spectra of L-Lys, TiO2, and L-Lys on TiO2 in
Figure S2 revealed that adsorbed L-Lys on TiO2 significantly suppressed the hydroxyl groups (-
OH) on TiO2 in 3600 – 3800 cm-1.11, 57 Significant differences in IR features of amine and
carboxylic bands in adsorbed L-Lys during pretreatment in Figure S2 (b) and Figure S3 further
suggest that the majority of adsorbed L-Lys on the TiO2 surface and those L-Lys on the top of
adsorbed L-Lys were perturbed. Attaining 12.89% of conversion in S-S photocatalysis shown in
Figure 4 and Table 2 further supports that a very high fraction of IR signals obtained are from
adsorbed L-Lys since less than 20% of L-Lys/TiO2 mixture in the DRIFTs cell was exposed to UV
irradiation.
Pretreatment removed the water content on L-Lys and L-Lys/TiO2 as evidence by attenuation of a
broad water band in 3000 – 3600 cm-1 and hydroxyl groups (-OH) on TiO2 in 3600 – 3800 cm-1.
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Removal of adsorbed H2O can be clearly observed by the IR spectra in Figure S3 at pretreatment.
It should be noted that the broad H2O band is a result of hydrogen bonding between adsorbed H2O
and L-Lys/TiO2. The decreases in the intensities of Ti-OH were observed, corresponding to the
linear, double, and triple bonded -OH on TiO2, respectively, which resulted from the removal of
adsorbed H2O on TiO2. Removal of adsorbed H2O also sharpened the asymmetric vibration mode
of -NH2 at 3361 cm-1.
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The specific structures of adsorbed L-Lys on the basis of the relative intensity of the bands in 1400
– 1700 cm-1 are summarized in Table 1.42, 47, 55-56 Both L-Lys and L-Lys/P-25 have a zwitterionic
structure which the primary amine (-NH2) on ε-carbon has been protonated. L-Lys/P-25 presented
a strong interaction between L-Lys and P-25 as evidenced by the diminishing of linear hydroxyl
group (-OH) at 3735 cm-1. L-Lys/rutile and L-Lys/anatase gave cationic and di-cationic structures,
in which both amino groups were protonated, exhibiting a low intensity of -NH2 at 3361 cm-1
related to that of L-Lys and L-Lys/P-25. In spite of this similarity in NH2 protonation, L-Lys/rutile
contains a -COO- whereas L-Lys/anatase contains a -COOH.
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L-Lys/Anatase: di-cationic
and cationic
1683, 1612, 1570, 1521, and
1411 cm-1
before pret.
after pret.
H
+H3N
C
COOH
9
(CH2)4
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+
NH3
L-Lys/Anatase
2
1
0
L-Lys/Rutile: cationic
1612,1570, 1521, and 1411 cm-1
H
+H3N
C
COO-
(CH2)4
+
NH3
L-Lys/Rutile
L-Lys/P-25: zwitterionic
1612, 1521 and 1411 cm-1
H
H2N
C
COO-
L-Lys/P-25
(CH2)4
+
NH3
L-Lys
L-Lys: zwitterionic
1612, 1521 and 1411 cm-1
H
H2N
C
COO-
(CH2)4
+
NH3
4000
3500
3000
2500
2000
1500
1000
Wavenumber (cm-1)
Figure 3. IR 1/SB spectra of L-Lys and L-Lys/TiO2 before and after pretreatment in step (i). The
spectra were obtained by log(1/ISB), where ISB is the intensity of the single-beam spectrum. -NH2
at 3361 and 3282 cm-1 and NH3 at 1570 and 1521 cm-1 were highlighted by blue; -COOH at 1683
+
cm-1 and COO- 1612 and 1411 cm-1 were highlighted by red; the hydrogen bonding between NH3
+
and COO- were highlighted by pink; Ti-OH at 3735, 3693, and 3635 cm-1 were labeled in grey; C-
H from L-Lys at 2927 cm-1 was labeled in black.
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Table 1. IR band assignments of adsorbed L-Lys on TiO2.42, 47, 55-56
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8
IR peaks
1683
Assignments
Structures (IR intensity) [a]
Di-cationic
C=O stretching of COOH
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Asymmetric stretching of COO-
Asymmetric deformation of NH3
Di-cationic (weak), cationic
1612
1570
+
(medium), zwitterionic (strong)
Bending of NH2
Anionic (strong)
Di-cationic (strong), cationic
(strong)
+
1570
Symmetric deformation of NH3
Cationic (weak), zwitterionic
(strong)
+
1521
1411
Symmetric deformation of NH3
Cationic (strong), zwitterionic
(strong), anionic (strong)
Symmetric stretching of COO-
[a]. IR intensity: weak, medium, and strong
Solid-solid photocatalytic reactions (solvent-free)
UV irritation on adsorbed L-Lys on various forms of TiO2 led to variations in their IR spectra,
shown in Figure 4 (a), of which corresponding absorbance spectra in Figure 4 (b). Rutile did not
show any photocatalytic activity as evidenced by constant IR profiles throughout UV-irradiation.
Rutile is known to exhibit very lower oxidative activities because of its low oxidative potential
and lack of mobile OH groups.58-60
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L-Lys/anatase showed little variations in the intensity of NH2 before and after UV irradiation as
shown in Figure 4 (b) which indicates PCA product was not produced. However, UV irradiation
led to a rising structureless band in 1000 – 2500 cm-1, indicating the occurrence of accumulation
of photogenerated electrons under UV irradiation.10-11 The accumulated photogenerated electrons
on anatase can be attributed to the breaking of the C-H bond at 2927 cm-1, which proceed through
the following steps in Equation 1.
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―
+
―
+
―
(
)
(
)
(
)
(1)
TiO2 +ℎ푣 → TiO2 푒 , ℎ ; TiO2 푒 , ℎ + NH2CHR1R2 → TiO2 푒 + NH2CHR1R2
Terminating UV allowed the structureless IR band gradually returning to the initial base spectrum.
No discernable adsorbed and gaseous products were observed. The lack of activity of anatase for
L-Lys conversion is indeed surprising since anatase has been shown to be highly active in
oxidation because of high energy levels of valence band.58-61 The oxidative activity of anatase
should have initiated the oxidation of the amino group in L-Lys to imine. The lack of anatase
activities could be attributed to the di-cationic form of adsorbed L-Lys. The positive charge of -
+
NH3 in the di-cationic L-Lys/anatase would expel photogenerated holes, inhibiting a hole-
initiating reaction step. We further verified the activities of anatase and rutile by ex situ studies
which do not produce any detectable products as shown by 1H NMR and circular dichroism (CD),
in Figure S4.
UV-irradiation on L-Lys/P-25 produced pronounced decreases in -NH2 at 3361 cm-1 and hydroxyl
groups at 3693 and 3634 cm-1, and variations in a number of bands in 1400 – 1700 cm-1 as well as
an immediate rise in the structureless IR band (i.e., rising IR intensity in 1000 – 2500 cm-1) in
Figure 4 (b) inset. The structureless band is a result of the accumulation of photogenerated
electrons (e-) at shallow levels and conduction bands.10-11 The distribution of e- in the conduction-
band and shallow level can be estimated by fitting the IR profiles to simulated models of electrons
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(e-CB) and (e-ST).10-11 The fitting results showed that L-Lys/P-25 produced over 80 % of
photogenerated electrons in the conduction band and Lys/anatase produced less than 40% in the
conduction band. The dynamic behavior of the conduction band and trapped electrons will be
+…-
further studied. The decrease in the IR intensity of NH2 at 3361 cm-1 and hydrogen bonded NH3
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OOC at in 2000 – 2800 cm-1 provided a direct evidence of conversion of -NH2 in L-Lys. An
increase of 1683 cm-1 reflected the formation of C=O, a carboxylate group in PCA, the final
product. We attributed the activity of P-25 to its ability to allow the electron/hole transfer among
rutile, anatase, and adsorbed L-Lys.62-69 The formation of racemic PCA from L-Lys/P-25 was
further confirmed by 1H-NMR and CD in Figure 6 and ESI-MS in Figure S5.
L-PCA is a desirable product from L-Lys. It is interesting to note that L-PCA and racemic PCA
have the same chemical structure, but their adsorbed states gave different IR features in Figure S6.
L-PCA preferably adsorbed on rutile, anatase, and P-25 TiO2 in a zwitterionic structure which
possesses a hydrogen-bonded NH2 …-OOC at 2319 cm-1. In addition to the IR feature of broad
+
board hydrogen bonding, the absence of isolated carboxylic acid at 1683 cm-1 indicates the
presence of a zwitterionic L-PCA on TiO2. In contrast, the observation of a prominent carboxylic
acid (-C=O) at 1683 on P-25 in Figure 4 (b) indicates the presence of racemic PCA, which was
further verified by 1H NMR and CD in Figure 6.
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(a)
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0.5
UV on at 0 min
UV on at 10 min
UV off at 10 min
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L-Lys/Anatase
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L-Lys/Rutile
L-Lys/P25
(b)
L-Lys/Anatase
0.25
L-Lys/Rutile
L-Lys/P-25
0.1
2.00 min
0.25 min
0.05 min
0.02 min
4000
3500
3000
2500
2000
1500
1000
Wavenumber (cm-1)
Figure 4. (a) IR 1/Single beam spectra and (b) absorbance spectra of L-Lys/P-25, L-Lys/rutile,
and L-Lys/anatase during S-S photocatalytic reaction. The absorbance spectra were obtained by
log(I0/I), where I is the IR single-beam intensity in step (ii) under UV irradiation and I0 is the IR
single-beam intensity obtained in step (i) after pretreatment. Inset: IR absorbance spectra of L-
Lys/P-25 during UV irradiation. The IR spectrum of UV on at 0 min was applied as a background.
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Liquid-solid (L-S) photocatalytic reaction in an aqueous environment
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Figure 5 shows IR absorbance spectra of L-S photocatalytic reaction on P-25 obtained from in situ
FTIR-ATR study illustrated in Figure 2 (c). The structureless band of photogenerated electrons
observed in the S-S reaction was also found in the L-S reaction. In contrast to S-S reaction shown
in Figure 4 (b), L-S produced a very low-intensity band at 1668 cm-1, indicating a lack of formation
of racemic PCA. CD analysis in Figure 6 (b) showed that the standard L-Lys and L-PCA absorbed
light at 211 and 208 nm, respectively. The product from L-S reaction exhibited the feature of L-
PCA, which showed a positive peak at 208 nm. The absence of CD peak indicates the formation
of racemic PCA in S-S reaction, which did not absorb polarized light. Table 2 showed that the
L-S reaction in an aqueous environment produced more than 50% e.e. of L-PCA. The S-S reaction
produced about 10% e.e. Modification of photocatalyst by adding noble metals and adding a buffer
in L-Lys solution could improve the optical purity of product to around 70% in photocatalytic
reaction.28-29 Although the synthesis of L-PCA in enzymatic systems achieved over 99% e.e.,
these processes suffered from several drawbacks: (i) complicated procedures, (ii) high cost of
catalysts or starting materials, and (iii) difficulty in separation.37, 70
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Figure 5. IR absorbance spectra of L-Lys/P-25 at in situ L-S photocatalytic reaction on ATR. The
absorbance spectra were obtained by log(I0/I), where I is the IR single-beam intensity under UV
irradiation in step (ii) and I0 is the IR single-beam intensity of the pretreated sample collected at
the end of pretreatment in step (i). The high noise level in the IR spectra can be attributed to
deposition of less than 25 nm thickness of P-25 on the Ge window in ATR.
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Figure 6. (a) H NMR of standard L-Lys, standard L-PCA, and products and (b) Circular
dichroism spectra from in situ solid-solid and ex situ liquid-solid photocatalytic reactions of L-
Lys/P-25.
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Table 2. Properties of photocatalytic reaction on P-25/L-Lys
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Conversion %[a]
e.e. (AL-AD)/(AL+AD)[b] Reaction time
Rate
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Process
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PCA/initial L-Lys
CD
CD/UV
0.61
min
µmol/min
Ex situ L-S
reaction
18.93
12.89
0.51
60.00
3.15
8.76
In situ S-S
reaction
0.08
0.10
10.00[c]
[a] Estimated from MS intensity in Table S2.
[b] Enantiomer excess: calibrated from standard solution and UV-vis in Table S3.
Aqueous environment altered the reaction pathway on P-25 from the formation of racemic PCA
to that of L-PCA. Further examination of IR spectra of L-Lys on P-25 TiO2 from a S-S reaction
environment to an L-S reaction (i.e., aqueous) environment by increasing the amount of H2O in
Figure 7 shows that water altered the structure of adsorbed L-Lys from a zwitterionic form to an
anionic form. An anionic form of adsorbed L-Lys allowed its hydrogen in α-NH2 to be abstracted
by the photogenerated hole, facilitating the reaction to proceed through the ε route in Scheme 1,
leading to L-PCA.28, 31-32 Altering the structure of adsorbed L-Lys can be attributed to the change
in pH value of the reaction solution. The pH of the solution has been found to govern the structure
of adsorbed CO2 on ZnS, controlling the reaction pathway.71-72
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Dry L-Lys/P-25
2
1
0
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(zwitterionic)
H
H2N
C
COO-
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(CH2)4
+
NH3
L-Lys/P-25 after pret.
H2O/D2O
(aq.)
L-Lys/P-25 before pret.
H
C
H2N
COO-
L-Lys/P-25 flow
H2O vapor
(CH2)4
NH2
Aqueous L-Lys/P-25
solution
L-Lys/P-25 in D2O
(anionic)
4000
3500
3000 2000
1500
1000
Wavenumber (cm-1)
Figure 7. IR 1/SB spectra of L-Lys/P-25 with increasing amounts of water.
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Conclusions
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In this study, we unraveled the complexity of the effect of TiO2 crystalline structures and reaction
environment (i.e., conditions of reaction process) on the rate and chiral selectivity of photocatalytic
conversion of L-Lys to PCA. In a solvent-free environment, L-Lys adsorbed on anatase and rutile
as di-cationic and cationic structures, in which the strong hydrogen bonding of NH3+…-OOC and
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+
NH3+…NH3 inhibits the oxidation of either ε or α amino groups. P-25, a mixed phase of
anatase/rutile, adsorbed L-Lys as a zwitterionic species, which favors α pathway, producing
racemic PCA. In an aqueous environment, L-Lys adsorbed on P-25 in an anionic form which
favors the ε reaction route, leading to the formation of L-PCA, a desirable product. This study
shed the light into how the conditions of a reaction process affect the structure of adsorbed
reactants on the catalyst surfaces, altering the reaction pathway and chirality of the final products.
The results obtained in this study could open up a new low-cost route to the synthesis of high
valued-added amino acid.
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ASSOCIATED CONTENT
Supporting Information
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The supporting Information is available free of charge on the ACS Publications website.
Further details about the IR spectra of L-Lys and L-Lys/TiO2 at pretreatment, CD, and 1H NMR
of samples, ESI-MS spectra of products from liquid-solid and solid-solid photocatalytic reaction,
the IR spectra of adsorbed L-PCA and racemic PCA on TiO2, and the calibration of e.e. from UV-
vis and CD.
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AUTHOR INFORMATION
Corresponding Authors
*schuang@uakron.edu
Notes
The authors declare no competing financial interests.
ACKNOWLEDGMENT
This work was partially supported by The University of Akron Faculty Initiation Fund and First
Energy Advanced Energy Research Center. The authors thank Ms. Baiping Ren and Dr. Jie Zheng
for their help on the circular dichroism characterization.
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