Experimental methods capable of selectively probing water at the DNA minor groove, major groove, and phosphate backbone are crucial for understanding how hydration influences DNA structure and function. Chiral-selective sum frequency generation spectroscopy (chiral SFG) is unique among vibrational spectroscopies because it can selectively probe water molecules that form chiral hydration structures around biomolecules. However, interpreting chiral SFG spectra is challenging since both water and the biomolecule can produce chiral SFG signals. Here, we combine experiment and computation to establish a theoretical framework for the rigorous interpretation of chiral SFG spectra of DNA. We demonstrate that chiral SFG detects the N–H stretch of DNA base pairs and the O–H stretch of water, exclusively probing water molecules in the DNA first hydration shell. Our analysis reveals that DNA transfers chirality to water molecules only within the first hydration shell, so they can be probed by chiral SFG spectroscopy. Beyond the first hydration shell, the electric field-induced water structure is symmetric and, therefore, precludes chiral SFG response. Furthermore, we find that chiral SFG can differentiate chiral subpopulations of first hydration shell water molecules at the minor groove, major groove, and phosphate backbone. Our findings challenge the scientific perspective dominant for more than 40 years that the minor groove “spine of hydration” is the only chiral water structure surrounding the DNA double helix. By identifying the molecular origins of the DNA chiral SFG spectrum, we lay a robust experimental and theoretical foundation for applying chiral SFG to explore the chemical and biological physics of DNA hydration.
REFERENCES
1.
J. D.
Watson
and F. H.
Crick
, “Molecular structure of nucleic acids: A structure for deoxyribose nucleic acid
,” Nature
171
(4356
), 737
–738
(1953
).2.
R.
Dickerson
, H.
Drew
, and B.
Conner
, Biomolecular Stereodynamics
(Adenine Press
, 1981
).3.
M. L.
Kopka
, A. V.
Fratini
, H. R.
Drew
, and R. E.
Dickerson
, “Ordered water structure around a B-DNA dodecamer: A quantitative study
,” J. Mol. Biol.
163
(1
), 129
–146
(1983
).4.
V. P.
Chuprina
, “Anomalous structure and properties of poly (dA)·poly(dT). Computer simulation of the polynucleotide structure with the spine of hydration in the minor groove
,” Nucleic Acids Res.
15
(1
), 293
–311
(1987
).5.
E.
Liepinsh
, G.
Otting
, and K.
Wüthrich
, “NMR observation of individual molecules of hydration water bound to DNA duplexes: Direct evidence for a spine of hydration water present in aqueous solution
,” Nucleic Acids Res.
20
(24
), 6549
–6553
(1992
).6.
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
).7.
E.
Duboué-Dijon
, A. C.
Fogarty
, J. T.
Hynes
, and D.
Laage
, “Dynamical disorder in the DNA hydration shell
,” J. Am. Chem. Soc.
138
(24
), 7610
–7620
(2016
).8.
N. J.
Tao
, S. M.
Lindsay
, and A.
Rupprecht
, “Structure of DNA hydration shells studied by Raman spectroscopy
,” Biopolymers
28
(5
), 1019
–1030
(1989
).9.
P.
Perera
, M.
Wyche
, Y.
Loethen
, and D.
Ben-Amotz
, “Solute-induced perturbations of solvent-shell molecules observed using multivariate Raman curve resolution
,” J. Am. Chem. Soc.
130
(14
), 4576
–4577
(2008
).10.
T.
Elsaesser
, J.
Schauss
, A.
Kundu
, and B. P.
Fingerhut
, “Phosphate vibrations probe electric fields in hydrated biomolecules: Spectroscopy, dynamics, and interactions
,” J. Phys. Chem. B
125
(15
), 3899
–3908
(2021
).11.
A. K.
Singh
, C.
Wen
, S.
Cheng
, and N. Q.
Vinh
, “Long-range DNA-water interactions
,” Biophys. J.
120
(22
), 4966
–4979
(2021
).12.
S. K.
Pal
, L.
Zhao
, and A. H.
Zewail
, “Water at DNA surfaces: Ultrafast dynamics in minor groove recognition
,” Proc. Natl. Acad. Sci. U. S. A.
100
(14
), 8113
(2003
).13.
M.
Yang
, Ł.
Szyc
, and T.
Elsaesser
, “Decelerated water dynamics and vibrational couplings of hydrated DNA mapped by two-dimensional infrared spectroscopy
,” J. Phys. Chem. B
115
(44
), 13093
–13100
(2011
).14.
D.
Laage
, T.
Elsaesser
, and J. T.
Hynes
, “Water dynamics in the hydration shells of biomolecules
,” Chem. Rev.
117
(16
), 10694
–10725
(2017
).15.
G. W. H.
Wurpel
, M.
Sovago
, and M.
Bonn
, “Sensitive probing of DNA binding to a cationic lipid monolayer
,” J. Am. Chem. Soc.
129
(27
), 8420
–8421
(2007
).16.
P. C.
Singh
, M.
Ahmed
, S.
Nihonyanagi
, S.
Yamaguchi
, and T.
Tahara
, “DNA-induced reorganization of water at model membrane interfaces investigated by heterodyne-detected vibrational sum frequency generation spectroscopy
,” J. Phys. Chem. B
126
(4
), 840
–846
(2022
).17.
N. M.
Levinson
, E. E.
Bolte
, C. S.
Miller
, S. A.
Corcelli
, and S. G.
Boxer
, “Phosphate vibrations probe local electric fields and hydration in biomolecules
,” J. Am. Chem. Soc.
133
(34
), 13236
–13239
(2011
).18.
E. A.
Perets
and E. C. Y.
Yan
, “The H2O helix: The chiral water superstructure surrounding DNA
,” ACS Cent. Sci.
3
(7
), 683
–685
(2017
).19.
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
).20.
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
(2020
).21.
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
).22.
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
).23.
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
(2005
).24.
Z.
Wang
, L.
Fu
, and E. C. Y.
Yan
, “C–H stretch for probing kinetics of self-assembly into macromolecular chiral structures at interfaces by chiral sum frequency generation spectroscopy
,” Langmuir
29
(12
), 4077
–4083
(2013
).25.
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
).26.
E. A.
Perets
, P. E.
Videla
, E. C. Y.
Yan
, and V. S.
Batista
, “Chiral inversion of amino acids in antiparallel β-sheets at interfaces probed by vibrational sum frequency generation spectroscopy
,” J. Phys. Chem. B
123
(27
), 5769
–5781
(2019
).27.
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
).28.
E. A.
Perets
, K. B.
Olesen
, and E. C. Y.
Yan
, “Chiral sum frequency generation spectroscopy detects double-helix DNA at interfaces
,” Langmuir
38
(18
), 5765
–5778
(2022
).29.
G. J.
Simpson
, “Molecular origins of the remarkable chiral sensitivity of second-order nonlinear optics
,” ChemPhysChem
5
(9
), 1301
–1310
(2004
).30.
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
).31.
G. J.
Simpson
, Nonlinear Optical Polarization Analysis in Chemistry and Biology
(Cambridge University Press
, 2017
).32.
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
).33.
D.
Konstantinovsky
, T.
Santiago
, M.
Tremblay
, G. J.
Simpson
, S.
Hammes-Schiffer
, and E. C. Y.
Yan
, “Theoretical basis for interpreting heterodyne chirality-selective sum frequency generation spectra of water
,” J. Chem. Phys.
160
(5
), 055102
(2024
).34.
Z.
Li
, C. N.
Weeraman
, M. S.
Azam
, E.
Osman
, and J. M.
Gibbs-Davis
, “The thermal reorganization of DNA immobilized at the silica/buffer interface: A vibrational sum frequency generation investigation
,” Phys. Chem. Chem. Phys.
17
(19
), 12452
–12457
(2015
).35.
S.-Y.
Jung
, S.-M.
Lim
, F.
Albertorio
, G.
Kim
, M. C.
Gurau
, R. D.
Yang
, M. A.
Holden
, and P. S.
Cremer
, “The Vroman effect: A molecular level description of fibrinogen displacement
,” J. Am. Chem. Soc.
125
(42
), 12782
–12786
(2003
).36.
M.
Yang
, Ł.
Szyc
, and T.
Elsaesser
, “Femtosecond two-dimensional infrared spectroscopy of adenine-thymine base pairs in DNA oligomers
,” J. Phys. Chem. B
115
(5
), 1262
–1267
(2011
).37.
A.
Morita
and J. T.
Hynes
, “A theoretical analysis of the sum frequency generation spectrum of the water surface. II. Time-dependent approach
,” J. Phys. Chem. B
106
(3
), 673
–685
(2002
).38.
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
).39.
B. M.
Auer
and J. L.
Skinner
, “IR and Raman spectra of liquid water: Theory and interpretation
,” J. Chem. Phys.
128
(22
), 224511
(2008
).40.
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
).41.
P. A.
Pieniazek
, C. J.
Tainter
, and J. L.
Skinner
, “Interpretation of the water surface vibrational sum-frequency spectrum
,” J. Chem. Phys.
135
(4
), 044701
(2011
).42.
D.
Konstantinovsky
, E. C. Y.
Yan
, and S.
Hammes-Schiffer
, “Characterizing interfaces by Voronoi tessellation
,” J. Phys. Chem. Lett.
14
(23
), 5260
–5266
(2023
).43.
A.
Rosu-Finsen
, “Interfacial interpretation
,” Nat. Rev. Chem
7
(7
), 461
(2023
).44.
Y.-C.
Wen
, S.
Zha
, X.
Liu
, S.
Yang
, P.
Guo
, G.
Shi
, H.
Fang
, Y. R.
Shen
, and C.
Tian
, “Unveiling microscopic structures of charged water interfaces by surface-specific vibrational spectroscopy
,” Phys. Rev. Lett.
116
(1
), 016101
(2016
).45.
S.
Pezzotti
, D. R.
Galimberti
, Y. R.
Shen
, and M.-P.
Gaigeot
, “Structural definition of the BIL and DL: A new universal methodology to rationalize non-linear χ(2)(ω) SFG signals at charged interfaces, including χ(3)(ω) contributions
,” Phys. Chem. Chem. Phys.
20
(7
), 5190
–5199
(2018
).46.
T.
Joutsuka
, T.
Hirano
, M.
Sprik
, and A.
Morita
, “Effects of third-order susceptibility in sum frequency generation spectra: A molecular dynamics study in liquid water
,” Phys. Chem. Chem. Phys.
20
(5
), 3040
–3053
(2018
).47.
P. E.
Ohno
, H.-f.
Wang
, and F. M.
Geiger
, “Second-order spectral lineshapes from charged interfaces
,” Nat. Commun.
8
(1
), 1032
(2017
).48.
A. M.
Darlington
, T. A.
Jarisz
, E. L.
DeWalt-Kerian
, S.
Roy
, S.
Kim
, M. S.
Azam
, D. K.
Hore
, and J. M.
Gibbs
, “Separating the pH-dependent behavior of water in the stern and diffuse layers with varying salt concentration
,” J. Phys. Chem. C
121
(37
), 20229
–20241
(2017
).49.
K. E.
Furse
and S. A.
Corcelli
, “Effects of an unnatural base pair replacement on the structure and dynamics of DNA and neighboring water and ions
,” J. Phys. Chem. B
114
(30
), 9934
–9945
(2010
).50.
Y. R.
Shen
, “Surface properties probed by second-harmonic and sum-frequency generation
,” Nature
337
(6207
), 519
–525
(1989
).51.
N.
Ji
, V.
Ostroverkhov
, C.-Y.
Chen
, and Y.-R.
Shen
, “Phase-sensitive sum-frequency vibrational spectroscopy and its application to studies of interfacial alkyl chains
,” J. Am. Chem. Soc.
129
(33
), 10056
–10057
(2007
).52.
Y. R.
Shen
, “Phase-sensitive sum-frequency spectroscopy
,” Annu. Rev. Phys. Chem.
64
(1
), 129
–150
(2013
).53.
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
).54.
S.-L.
Chen
, L.
Fu
, W.
Gan
, and H.-F.
Wang
, “Homogeneous and inhomogeneous broadenings and the Voigt line shapes in the phase-resolved and intensity sum-frequency generation vibrational spectroscopy
,” J. Chem. Phys.
144
(3
), 034704
(2016
).55.
A. T.
Krummel
and M. T.
Zanni
, “Interpreting DNA vibrational circular dichroism spectra using a coupling model from two-dimensional infrared spectroscopy
,” J. Phys. Chem. B
110
(48
), 24720
–24727
(2006
).56.
C.
Greve
, N. K.
Preketes
, H.
Fidder
, R.
Costard
, B.
Koeppe
, I. A.
Heisler
, S.
Mukamel
, F.
Temps
, E. T. J.
Nibbering
, and T.
Elsaesser
, “N–H stretching excitations in adenosine-thymidine base pairs in solution: Pair geometries, infrared line shapes, and ultrafast vibrational dynamics
,” J. Phys. Chem. A
117
(3
), 594
–606
(2013
).57.
J.-D.
Chai
and M.
Head-Gordon
, “Long-range corrected hybrid density functionals with damped atom–atom dispersion corrections
,” Phys. Chem. Chem. Phys.
10
(44
), 6615
–6620
(2008
).58.
T. H.
Dunning
, Jr., “Gaussian basis sets for use in correlated molecular calculations. I. The atoms boron through neon and hydrogen
,” J. Chem. Phys.
90
(2
), 1007
–1023
(1989
).59.
M. J.
Frisch
, G. W.
Trucks
, H. B.
Schlegel
, G. E.
Scuseria
, M. A.
Robb
, J. R.
Cheeseman
, G.
Scalmani
, V.
Barone
, G. A.
Petersson
, H.
Nakatsuji
, X.
Li
, M.
Caricato
, A.
Marenich
, J.
Bloino
, B. G.
Janesko
, R.
Gomperts
, B.
Mennucci
, H. P.
Hratchian
, J. V.
Ortiz
, A. F.
Izmaylov
, J. L.
Sonnenberg
, D.
Williams-Young
, F.
Ding
, F.
Lipparini
, F.
Egidi
, J.
Goings
, B.
Peng
, A.
Petrone
, T.
Henderson
, D.
Ranasinghe
, V. G.
Zakrzewski
, J.
Gao
, N.
Rega
, G.
Zheng
, W.
Liang
, M.
Hada
, M.
Ehara
, K.
Toyota
, R.
Fukuda
, J.
Hasegawa
, M.
Ishida
, T.
Nakajima
, Y.
Honda
, O.
Kitao
, H.
Nakai
, T.
Vreven
, K.
Throssell
, J. A.
Montgomery
, Jr., J. E.
Peralta
, F.
Ogliaro
, M.
Bearpark
, J. J.
Heyd
, E.
Brothers
, K. N.
Kudin
, V. N.
Staroverov
, T.
Keith
, R.
Kobayashi
, J.
Normand
, K.
Raghavachari
, A.
Rendell
, J. C.
Burant
, S. S.
Iyengar
, J.
Tomasi
, M.
Cossi
, J. M.
Millam
, M.
Klene
, C.
Adamo
, R.
Cammi
, J. W.
Ochterski
, R. L.
Martin
, K.
Morokuma
, O.
Farkas
, J. B.
Foresman
, and D. J.
Fox
, Gaussian 16, Revision C.02, Gaussian, Inc.
, Wallingford, CT
, 2016
.60.
C. S.
Peng
, K. C.
Jones
, and A.
Tokmakoff
, “Anharmonic vibrational modes of nucleic acid bases revealed by 2D IR spectroscopy
,” J. Am. Chem. Soc.
133
(39
), 15650
–15660
(2011
).61.
J. J.
Ho
, D. R.
Skoff
, A.
Ghosh
, and M. T.
Zanni
, “Structural characterization of single-stranded DNA monolayers using two-dimensional sum frequency generation spectroscopy
,” J. Phys. Chem. B
119
(33
), 10586
–10596
(2015
).62.
P.
Hamm
and M.
Zanni
, Concepts and Methods of 2D Infrared Spectroscopy
(Cambridge University Press
, 2011
).63.
A. T.
Krummel
and M. T.
Zanni
, “DNA vibrational coupling revealed with two-dimensional infrared spectroscopy: Insight into why vibrational spectroscopy is sensitive to DNA structure
,” J. Phys. Chem. B
110
(28
), 13991
–14000
(2006
).64.
C.
Lee
, K.-H.
Park
, and M.
Cho
, “Vibrational dynamics of DNA. I. Vibrational basis modes and couplings
,” J. Chem. Phys.
125
(11
), 114508
(2006
).65.
J.-H.
Choi
and M.
Cho
, “Computational IR spectroscopy of water: OH stretch frequencies, transition dipoles, and intermolecular vibrational coupling constants
,” J. Chem. Phys.
138
(17
), 174108
(2013
).66.
J.-H.
Choi
, S.
Ham
, and M.
Cho
, “Local amide I mode frequencies and coupling constants in polypeptides
,” J. Phys. Chem. B
107
(34
), 9132
–9138
(2003
).67.
M. L.
Clark
, A.
Ge
, P. E.
Videla
, B.
Rudshteyn
, C. J.
Miller
, J.
Song
, V. S.
Batista
, T.
Lian
, and C. P.
Kubiak
, “CO2 reduction catalysts on gold electrode surfaces influenced by large electric fields
,” J. Am. Chem. Soc.
140
(50
), 17643
–17655
(2018
).68.
A.
Ge
, B.
Rudshteyn
, P. E.
Videla
, C. J.
Miller
, C. P.
Kubiak
, V. S.
Batista
, and T.
Lian
, “Heterogenized molecular catalysts: Vibrational sum-frequency spectroscopic, electrochemical, and theoretical investigations
,” Acc. Chem. Res.
52
(5
), 1289
–1300
(2019
).69.
L.
Bromley
, P. E.
Videla
, J. L.
Cartagena-Brigantty
, V. S.
Batista
, and L.
Velarde
, “Binding and orientation of carbamate pesticides on silica surfaces
,” J. Phys. Chem. C
127
(17
), 8399
–8410
(2023
).70.
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
, 189
–216
(2015
).71.
X.
Zhuang
, P. B.
Miranda
, D.
Kim
, and Y. R.
Shen
, “Mapping molecular orientation and conformation at interfaces by surface nonlinear optics
,” Phys. Rev. B
59
(19
), 12632
–12640
(1999
).72.
D. A.
Case
, H. M.
Aktulga
, K.
Belfon
, I.
Ben-Shalom
, S. R.
Brozell
, D.
Cerutti
, T.
Cheatham
III, G.
Cisneros
, V.
Cruzeiro
, and T.
Darden
, Amber 2021, University of California Press
, 2021
.73.
H. W.
Horn
, W. C.
Swope
, J. W.
Pitera
, J. D.
Madura
, T. J.
Dick
, G. L.
Hura
, and T.
Head-Gordon
, “Development of an improved four-site water model for biomolecular simulations: TIP4P-Ew
,” J. Chem. Phys.
120
(20
), 9665
–9678
(2004
).74.
M.
Zgarbová
, J.
Sponer
, M.
Otyepka
, T. E.
Cheatham
III, R.
Galindo-Murillo
, and P. J.
Jurecka
, “Refinement of the sugar–phosphate backbone torsion beta for AMBER force fields improves the description of Z- and B-DNA
,” J. Chem. Theory Comput.
11
(12
), 5723
–5736
(2015
).75.
T.
Darden
, D.
York
, and L.
Pedersen
, “Particle mesh Ewald: An N ⋅ log(N) method for Ewald sums in large systems
,” J. Chem. Phys.
98
(12
), 10089
–10092
(1993
).76.
J.-P.
Ryckaert
, G.
Ciccotti
, and H. J.
Berendsen
, “Numerical integration of the cartesian equations of motion of a system with constraints: Molecular dynamics of n-alkanes
,” J. Comput. Phys.
23
(3
), 327
–341
(1977
).77.
S.
Miyamoto
and P. A.
Kollman
, “Settle: An analytical version of the SHAKE and RATTLE algorithm for rigid water models
,” J. Comput. Chem.
13
(8
), 952
–962
(1992
).78.
E. F.
Pettersen
, T. D.
Goddard
, C. C.
Huang
, G. S.
Couch
, D. M.
Greenblatt
, E. C.
Meng
, and T. E.
Ferrin
, “UCSF Chimera—A visualization system for exploratory research and analysis
,” J. Comput. Chem.
25
(13
), 1605
–1612
(2004
).79.
N.
Michaud-Agrawal
, E. J.
Denning
, T. B.
Woolf
, and O.
Beckstein
, “MDAnalysis: A toolkit for the analysis of molecular dynamics simulations
,” J. Comput. Chem.
32
(10
), 2319
–2327
(2011
).80.
V.
Ramasubramani
, B. D.
Dice
, E. S.
Harper
, M. P.
Spellings
, J. A.
Anderson
, and S. C.
Glotzer
, “freud: A software suite for high throughput analysis of particle simulation data
,” Comput. Phys. Commun.
254
, 107275
(2020
).81.
C.
Rycroft
, “VORO++: A three-dimensional Voronoi cell library in C++
,” Chaos
19
, 041111
(2009
).© 2024 Author(s). Published under an exclusive license by AIP Publishing.
2024
Author(s)
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