Chirality-selective vibrational sum frequency generation (chiral SFG) spectroscopy has emerged as a powerful technique for the study of biomolecular hydration water due to its sensitivity to the induced chirality of the first hydration shell. Thus far, water O–H vibrational bands in phase-resolved heterodyne chiral SFG spectra have been fit using one Lorentzian function per vibrational band, and the resulting fit has been used to infer the underlying frequency distribution. Here, we show that this approach may not correctly reveal the structure and dynamics of hydration water. Our analysis illustrates that the chiral SFG responses of symmetric and asymmetric O–H stretch modes of water have opposite phase and equal magnitude and are separated in energy by intramolecular vibrational coupling and a heterogeneous environment. The sum of the symmetric and asymmetric responses implies that an O–H stretch in a heterodyne chiral SFG spectrum should appear as two peaks with opposite phase and equal amplitude. Using pairs of Lorentzian functions to fit water O–H stretch vibrational bands, we improve spectral fitting of previously acquired experimental spectra of model β-sheet proteins and reduce the number of free parameters. The fitting allows us to estimate the vibrational frequency distribution and thus reveals the molecular interactions of water in hydration shells of biomolecules directly from chiral SFG spectra.

1.
M. L.
McDermott
,
H.
Vanselous
,
S. A.
Corcelli
, and
P. B.
Petersen
, “
DNA’s chiral spine of hydration
,”
ACS Cent. Sci.
3
(
7
),
708
714
(
2017
).
2.
D.
Konstantinovsky
,
E. A.
Perets
,
T.
Santiago
,
L.
Velarde
,
S.
Hammes-Schiffer
, and
E. C. Y.
Yan
, “
Detecting the first hydration shell structure around biomolecules at interfaces
,”
ACS Cent. Sci.
8
(
10
),
1404
1414
(
2022
).
3.
E. A.
Perets
and
E. C. Y.
Yan
, “
Chiral water superstructures around antiparallel β-sheets observed by chiral vibrational sum frequency generation spectroscopy
,”
J. Phys. Chem. Lett.
10
(
12
),
3395
3401
(
2019
).
4.
E. C. Y.
Yan
,
E. A.
Perets
,
D.
Konstantinovsky
, and
S.
Hammes-Schiffer
, “
Detecting interplay of chirality, water, and interfaces for elucidating biological functions
,”
Acc. Chem. Res.
56
(
12
),
1494
1504
(
2023
).
5.
E. A.
Perets
,
D.
Konstantinovsky
,
L.
Fu
,
J.
Chen
,
H.-F.
Wang
,
S.
Hammes-Schiffer
, and
E. C. Y.
Yan
, “
Mirror-image antiparallel β-sheets organize water molecules into superstructures of opposite chirality
,”
Proc. Natl. Acad. Sci. U. S. A.
117
(
52
),
32902
32909
(
2020
).
6.
D.
Konstantinovsky
,
E. A.
Perets
,
E. C. Y.
Yan
, and
S.
Hammes-Schiffer
, “
Simulation of the chiral sum frequency generation response of supramolecular structures requires vibrational couplings
,”
J. Phys. Chem. B
125
(
43
),
12072
12081
(
2021
).
7.
J.
Wang
,
X.
Chen
,
M. L.
Clarke
, and
Z.
Chen
, “
Detection of chiral sum frequency generation vibrational spectra of proteins and peptides at interfaces in situ
,”
Proc. Natl. Acad. Sci. U. S. A.
102
(
14
),
4978
4983
(
2005
).
8.
G. Y.
Stokes
,
J. M.
Gibbs-Davis
,
F. C.
Boman
,
B. R.
Stepp
,
A. G.
Condie
,
S. T.
Nguyen
, and
F. M.
Geiger
, “
Making ‘sense’ of DNA
,”
J. Am. Chem. Soc.
129
(
24
),
7492
7493
(
2007
).
9.
E. C. Y.
Yan
,
L.
Fu
,
Z.
Wang
, and
W.
Liu
, “
Biological macromolecules at interfaces probed by chiral vibrational sum frequency generation spectroscopy
,”
Chem. Rev.
114
(
17
),
8471
8498
(
2014
).
10.
L.
Fu
,
J.
Liu
, and
E. C. Y.
Yan
, “
Chiral sum frequency generation spectroscopy for characterizing protein secondary structures at interfaces
,”
J. Am. Chem. Soc.
133
(
21
),
8094
8097
(
2011
).
11.
L.
Fu
,
Z.
Wang
, and
E. C. Y.
Yan
, “
Chiral vibrational structures of proteins at interfaces probed by sum frequency generation spectroscopy
,”
Int. J. Mol. Sci.
12
(
12
),
9404
9425
(
2011
).
12.
A. J.
Moad
and
G. J.
Simpson
, “
A unified treatment of selection rules and symmetry relations for sum-frequency and second harmonic spectroscopies
,”
J. Phys. Chem. B
108
(
11
),
3548
3562
(
2004
).
13.
G. J.
Simpson
, “
Molecular origins of the remarkable chiral sensitivity of second-order nonlinear optics
,”
ChemPhysChem
5
(
9
),
1301
1310
(
2004
).
14.
B. M.
Auer
and
J. L.
Skinner
, “
Dynamical effects in line shapes for coupled chromophores: Time-averaging approximation
,”
J. Chem. Phys.
127
(
10
),
104105
(
2007
).
15.
Y. R.
Shen
,
The Principles of Nonlinear Optics
(
Wiley
,
2003
).
16.
D. S.
Walker
and
G. L.
Richmond
, “
Understanding the effects of hydrogen bonding at the vapor–water interface: Vibrational sum frequency spectroscopy of H2O/HOD/D2O mixtures studied using molecular dynamics simulations
,”
J. Phys. Chem. C
111
(
23
),
8321
8330
(
2007
).
17.
Q.
Du
,
R.
Superfine
,
E.
Freysz
, and
Y. R.
Shen
, “
Vibrational spectroscopy of water at the vapor/water interface
,”
Phys. Rev. Lett.
70
(
15
),
2313
(
1993
).
18.
G. J.
Simpson
,
Nonlinear Optical Polarization Analysis in Chemistry and Biology
(
Cambridge University Press
,
Cambridge
,
2017
).
19.
H.-F.
Wang
,
L.
Velarde
,
W.
Gan
, and
L.
Fu
, “
Quantitative sum-frequency generation vibrational spectroscopy of molecular surfaces and interfaces: Lineshape, polarization, and orientation
,”
Annu. Rev. Phys. Chem.
66
(
1
),
189
216
(
2015
).
20.
B. M.
Auer
and
J. L.
Skinner
, “
IR and Raman spectra of liquid water: Theory and interpretation
,”
J. Chem. Phys.
128
(
22
),
224511
(
2008
).
21.
D.
Konstantinovsky
,
E. A.
Perets
,
T.
Santiago
,
K.
Olesen
,
Z.
Wang
,
A. V.
Soudackov
,
E. C. Y.
Yan
, and
S.
Hammes-Schiffer
, “
Design of an electrostatic frequency map for the NH stretch of the protein backbone and application to chiral sum frequency generation spectroscopy
,”
J. Phys. Chem. B
127
(
11
),
2418
2429
(
2023
).
22.
W. F.
DeGrado
and
J. D.
Lear
, “
Induction of peptide conformation at apolar water interfaces. 1. A study with model peptides of defined hydrophobic periodicity
,”
J. Am. Chem. Soc.
107
(
25
),
7684
7689
(
1985
).
23.
D. C.
Phillips
,
R. L.
York
,
O.
Mermut
,
K. R.
McCrea
,
R. S.
Ward
, and
G. A.
Somorjai
, “
Side chain, chain length, and sequence effects on amphiphilic peptide adsorption at hydrophobic and hydrophilic surfaces studied by sum-frequency generation vibrational spectroscopy and quartz crystal microbalance
,”
J. Phys. Chem. C
111
(
1
),
255
261
(
2007
).
24.
R. L.
York
,
W. K.
Browne
,
P. L.
Geissler
, and
G. A.
Somorjai
, “
Peptides adsorbed on hydrophobic surfaces—A sum frequency generation vibrational spectroscopy and modeling study
,”
Isr. J. Chem.
47
(
1
),
51
58
(
2007
).
25.
T.
Weidner
and
D. G.
Castner
, “
SFG analysis of surface bound proteins: A route towards structure determination
,”
Phys. Chem. Chem. Phys.
15
(
30
),
12516
12524
(
2013
).
26.
L.
Fu
,
S.-L.
Chen
, and
H.-F.
Wang
, “
Validation of spectra and phase in sub-1 cm−1 resolution sum-frequency generation vibrational spectroscopy through internal heterodyne phase-resolved measurement
,”
J. Phys. Chem. B
120
(
8
),
1579
1589
(
2016
).
27.
J.-H.
Choi
,
S.
Hahn
, and
M.
Cho
, “
Amide I IR, VCD, and 2d IR spectra of isotope-labeled α-helix in liquid water: Numerical simulation studies
,”
Int. J. Quantum Chem.
104
(
5
),
616
634
(
2005
).
28.
Z.
Ganim
and
A.
Tokmakoff
, “
Spectral signatures of heterogeneous protein ensembles revealed by MD simulations of 2DIR spectra
,”
Biophys. J.
91
(
7
),
2636
2646
(
2006
).
29.
S.
Hahn
,
S.
Ham
, and
M.
Cho
, “
Simulation studies of amide I IR absorption and two-dimensional IR spectra of β hairpins in liquid water
,”
J. Phys. Chem. B
109
(
23
),
11789
11801
(
2005
).
30.
A. C.
Belch
and
S. A.
Rice
, “
The OH stretching spectrum of liquid water: A random network model interpretation
,”
J. Chem. Phys.
78
(
8
),
4817
4823
(
1983
).
31.
B. M.
Auer
and
J. L.
Skinner
, “
Vibrational sum-frequency spectroscopy of the water liquid/vapor interface
,”
J. Phys. Chem. B
113
(
13
),
4125
4130
(
2009
).
32.
J. R.
Schmidt
,
S. A.
Corcelli
, and
J. L.
Skinner
, “
Ultrafast vibrational spectroscopy of water and aqueous N-methylacetamide: Comparison of different electronic structure/molecular dynamics approaches
,”
J. Chem. Phys.
121
,
8887
(
2004
).
33.
S. A.
Corcelli
and
J. L.
Skinner
, “
Infrared and Raman line shapes of dilute HOD in liquid H2O and D2O from 10 to 90 °C
,”
J. Phys. Chem. A
109
(
28
),
6154
6165
(
2005
).
34.
P. A.
Pieniazek
,
C. J.
Tainter
, and
J. L.
Skinner
, “
Interpretation of the water surface vibrational sum-frequency spectrum
,”
J. Chem. Phys.
135
,
044701
(
2011
).
35.
T.
la Cour Jansen
and
J.
Knoester
, “
A transferable electrostatic map for solvation effects on amide I vibrations and its application to linear and two-dimensional spectroscopy
,”
J. Chem. Phys.
124
,
044502
(
2006
).
36.
T.
la Cour Jansen
,
A. G.
Dijkstra
,
T. M.
Watson
,
J. D.
Hirst
, and
J.
Knoester
, “
Modeling the amide I bands of small peptides
,”
J. Chem. Phys.
125
,
044312
(
2006
).
37.
S. A.
Corcelli
,
C. P.
Lawrence
, and
J. L.
Skinner
, “
Combined electronic structure/molecular dynamics approach for ultrafast infrared spectroscopy of dilute HOD in liquid H2O and D2O
,”
J. Chem. Phys.
120
(
17
),
8107
8117
(
2004
).
38.
D.
Konstantinovsky
,
E. C. Y.
Yan
, and
S.
Hammes-Schiffer
, “
Characterizing interfaces by Voronoi tessellation
,”
J. Phys. Chem. Lett.
14
(
23
),
5260
5266
(
2023
).

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