Temozolomide–Hesperetin Drug–Drug Cocrystal with Optimized Performance in Stability, Dissolution, and Tabletability

A new 1:1 drug–drug cocrystal of temozolomide and hesperetin was successfully prepared by liquid-assisted grinding, slurry conversion crystallization, and evaporation crystallization. The obtained cocrystal was comprehensively characterized by single-crystal and powder X-ray diffraction, differentia...

Full description

Saved in:
Bibliographic Details
Published inCrystal growth & design Vol. 21; no. 2; pp. 838 - 846
Main Authors Wang, Jie, Dai, Xia-Lin, Lu, Tong-Bu, Chen, Jia-Mei
Format Journal Article
LanguageEnglish
Published American Chemical Society 03.02.2021
Online AccessGet full text

Cover

Abstract A new 1:1 drug–drug cocrystal of temozolomide and hesperetin was successfully prepared by liquid-assisted grinding, slurry conversion crystallization, and evaporation crystallization. The obtained cocrystal was comprehensively characterized by single-crystal and powder X-ray diffraction, differential scanning calorimetry, and thermogravimetric analysis, as well as by Fourier transform infrared and nuclear magnetic resonance spectroscopy. The two drug molecules in the cocrystal are connected via O–H···O hydrogen bonds between the carbonyl oxygen of temozolomide and the phenolic hydroxyl group of hesperetin. The drug–drug cocrystal enhances the hydroscopic stability of hesperetin and the physicochemical stability of temozolomide. In addition, the cocrystal optimizes the dissolution behavior of temozolomide and hesperetin at pH 1.2 and pH 6.8 in comparison to the pristine drugs. Further, a compressibility assessment was also conducted, and the cocrystal exhibits a superior tabletability in comparison with temozolomide. Therefore, the drug–drug cocrystal has the potential to be developed as an efficient oral formulation of a drug combination which will overcome the weaknesses of each parent drug.
AbstractList A new 1:1 drug–drug cocrystal of temozolomide and hesperetin was successfully prepared by liquid-assisted grinding, slurry conversion crystallization, and evaporation crystallization. The obtained cocrystal was comprehensively characterized by single-crystal and powder X-ray diffraction, differential scanning calorimetry, and thermogravimetric analysis, as well as by Fourier transform infrared and nuclear magnetic resonance spectroscopy. The two drug molecules in the cocrystal are connected via O–H···O hydrogen bonds between the carbonyl oxygen of temozolomide and the phenolic hydroxyl group of hesperetin. The drug–drug cocrystal enhances the hydroscopic stability of hesperetin and the physicochemical stability of temozolomide. In addition, the cocrystal optimizes the dissolution behavior of temozolomide and hesperetin at pH 1.2 and pH 6.8 in comparison to the pristine drugs. Further, a compressibility assessment was also conducted, and the cocrystal exhibits a superior tabletability in comparison with temozolomide. Therefore, the drug–drug cocrystal has the potential to be developed as an efficient oral formulation of a drug combination which will overcome the weaknesses of each parent drug.
Author Dai, Xia-Lin
Chen, Jia-Mei
Lu, Tong-Bu
Wang, Jie
AuthorAffiliation Tianjin Key Laboratory of Drug Targeting and Bioimaging, School of Chemistry and Chemical Engineering
Institute for New Energy Materials and Low Carbon Technologies, School of Materials Science and Engineering
AuthorAffiliation_xml – name: Institute for New Energy Materials and Low Carbon Technologies, School of Materials Science and Engineering
– name: Tianjin Key Laboratory of Drug Targeting and Bioimaging, School of Chemistry and Chemical Engineering
Author_xml – sequence: 1
  givenname: Jie
  surname: Wang
  fullname: Wang, Jie
  organization: Institute for New Energy Materials and Low Carbon Technologies, School of Materials Science and Engineering
– sequence: 2
  givenname: Xia-Lin
  surname: Dai
  fullname: Dai, Xia-Lin
  email: 871098922@qq.com
  organization: Tianjin Key Laboratory of Drug Targeting and Bioimaging, School of Chemistry and Chemical Engineering
– sequence: 3
  givenname: Tong-Bu
  orcidid: 0000-0002-6087-4880
  surname: Lu
  fullname: Lu, Tong-Bu
  organization: Institute for New Energy Materials and Low Carbon Technologies, School of Materials Science and Engineering
– sequence: 4
  givenname: Jia-Mei
  orcidid: 0000-0002-3959-901X
  surname: Chen
  fullname: Chen, Jia-Mei
  email: chenjiamei@email.tjut.edu.cn
  organization: Tianjin Key Laboratory of Drug Targeting and Bioimaging, School of Chemistry and Chemical Engineering
BookMark eNp9kMFOAjEQhhuDiYievfYuC213ly5HAyomJJiI5023ncWS3S1pSwicfAff0CexG-BioqeZ_P98k5n_GnUa0wBCd5QMKGF0KKQbyJUaEEkoTeML1KUpyyKekrRz7pMsvkLXzq0JIXwUx120W0JtDqYytVbw_fk1A7cBC143eGq3q6C0BU-MtHvnRYV32n_gxcbrWh9A4VewpbG1aCTgwLx5UehK-30fT7Vzptp6bZo-Fo3CS1FUcPZv0GUpKge3p9pD70-Py8ksmi-eXyYP80gwzn2UJIQVPFWQKhGPRVlyKSgDNpZUFEnBM84YEdkYuAJSBrlMVcKSQkKhRkGJeyg97pXWOGehzKX2oj3KW6GrnJK8TS8P6eUhvfyUXuCGv7iN1bWw-3-I-yPRGmuztU3468_pH0NnilA
CitedBy_id crossref_primary_10_1021_acs_cgd_1c01016
crossref_primary_10_1016_j_molstruc_2022_134079
crossref_primary_10_1080_1061186X_2023_2300690
crossref_primary_10_1021_acs_cgd_2c00377
crossref_primary_10_1016_j_jddst_2024_106572
crossref_primary_10_1016_j_molstruc_2022_133746
crossref_primary_10_1039_D3CE00794D
crossref_primary_10_3390_pharmaceutics13060790
crossref_primary_10_1016_j_molstruc_2021_131848
crossref_primary_10_1016_j_ijpharm_2024_124789
crossref_primary_10_1039_D3CE01047C
crossref_primary_10_1039_D4RA06804A
crossref_primary_10_1016_j_xphs_2023_02_026
crossref_primary_10_1107_S205225252300266X
crossref_primary_10_3390_pharmaceutics14010023
crossref_primary_10_1016_j_molstruc_2023_134992
crossref_primary_10_1155_2023_6678252
crossref_primary_10_1016_j_molstruc_2024_138751
crossref_primary_10_3390_molecules27227998
crossref_primary_10_3390_pharmaceutics13122160
crossref_primary_10_1039_D1CE01609A
crossref_primary_10_4155_ppa_2022_0011
crossref_primary_10_1016_j_molstruc_2022_132665
crossref_primary_10_1039_D3CE00402C
crossref_primary_10_1007_s11094_024_03205_y
crossref_primary_10_1016_j_molliq_2023_121484
crossref_primary_10_1007_s13205_024_04123_2
crossref_primary_10_1016_j_jddst_2022_103757
crossref_primary_10_1021_acs_cgd_4c00145
crossref_primary_10_1016_j_molstruc_2024_140472
crossref_primary_10_3390_pharmaceutics14010094
crossref_primary_10_2174_1574892817666220913151252
crossref_primary_10_1021_acs_cgd_4c00220
crossref_primary_10_1007_s40843_023_2668_y
crossref_primary_10_1016_j_molstruc_2023_136086
crossref_primary_10_1021_acs_chemrev_1c00987
crossref_primary_10_1021_acsomega_4c07887
crossref_primary_10_3390_pharmaceutics14112486
crossref_primary_10_1016_j_molstruc_2022_133031
crossref_primary_10_1021_acs_cgd_3c00805
crossref_primary_10_3390_cryst12101337
crossref_primary_10_3390_ma15031244
crossref_primary_10_1016_j_cclet_2023_109032
crossref_primary_10_1016_j_molstruc_2022_133725
crossref_primary_10_1039_D3CE00473B
crossref_primary_10_1016_j_molliq_2023_122443
crossref_primary_10_1016_j_ijpharm_2023_123555
crossref_primary_10_1016_j_molstruc_2024_138577
crossref_primary_10_1021_acs_cgd_3c00520
crossref_primary_10_1016_j_molstruc_2023_135101
crossref_primary_10_2174_1567201819666220820115950
crossref_primary_10_1016_j_molstruc_2022_133135
crossref_primary_10_1039_D4MR00078A
crossref_primary_10_1016_j_xphs_2021_06_021
crossref_primary_10_1021_acs_molpharmaceut_3c01059
crossref_primary_10_1107_S2056989023006047
crossref_primary_10_1021_acs_cgd_1c00150
crossref_primary_10_1016_j_molstruc_2024_139719
crossref_primary_10_1016_j_jconrel_2022_12_042
crossref_primary_10_1016_j_ijpharm_2023_123666
crossref_primary_10_1021_acs_cgd_2c01073
crossref_primary_10_1155_2021_3834368
crossref_primary_10_1021_acs_molpharmaceut_4c00786
crossref_primary_10_1039_D1CE01327K
crossref_primary_10_3390_molecules29102208
crossref_primary_10_1016_j_jddst_2023_104568
crossref_primary_10_1021_acs_cgd_2c00866
Cites_doi 10.1021/cg300327x
10.1021/bi00197a003
10.1016/j.ijpharm.2015.12.001
10.1163/016942410X525678
10.1021/acs.cgd.6b01769
10.1016/S0305-7372(97)90019-0
10.1016/j.ijpharm.2012.10.043
10.1021/cg5018642
10.1021/cg400322t
10.1002/jps.21552
10.1007/s11095-007-9394-1
10.1021/acs.cgd.8b00807
10.1016/j.jpba.2019.05.035
10.1039/C5CC08216A
10.1007/s11060-015-1804-3
10.1039/c2ce25724f
10.1002/asia.200800070
10.4103/0253-7613.115015
10.1016/j.ejps.2015.10.006
10.1016/j.lwt.2018.04.056
10.1021/cg3002948
10.1016/j.drudis.2016.02.001
10.1016/j.ejps.2018.12.006
10.1021/acs.cgd.0c00326
10.1016/j.tiv.2013.12.002
10.1016/j.molstruc.2008.11.037
10.1002/jps.20262
10.1021/cg500327s
10.1016/j.jff.2013.05.006
10.18632/oncotarget.17401
10.1023/A:1011954800246
10.1021/jm00096a013
10.1017/S0007114510003910
10.1248/bpb.32.671
10.1016/j.ejps.2017.04.008
10.1039/c000614a
10.3390/cryst8020101
10.1093/neuonc/noy072
10.1002/asia.201200205
10.1080/01635581.2019.1638424
10.1248/cpb.42.1143
10.1107/S0108270187089510
10.1016/j.lwt.2019.03.059
10.1021/cg200704s
10.1016/j.tips.2012.12.003
10.3390/molecules181215344
10.1007/s40010-014-0142-8
10.1166/asl.2017.8486
ContentType Journal Article
Copyright 2021 American Chemical Society
Copyright_xml – notice: 2021 American Chemical Society
DBID AAYXX
CITATION
DOI 10.1021/acs.cgd.0c01153
DatabaseName CrossRef
DatabaseTitle CrossRef
DatabaseTitleList
DeliveryMethod fulltext_linktorsrc
Discipline Engineering
Chemistry
EISSN 1528-7505
EndPage 846
ExternalDocumentID 10_1021_acs_cgd_0c01153
a271203823
GroupedDBID 53G
55A
5GY
5VS
7~N
AABXI
ABMVS
ABPTK
ABUCX
ACGFS
ACS
AEESW
AENEX
AFEFF
ALMA_UNASSIGNED_HOLDINGS
AQSVZ
CS3
DU5
EBS
ED
ED~
F5P
GNL
IH9
JG
JG~
P2P
RNS
ROL
TN5
UI2
VF5
VG9
W1F
X
-~X
4.4
6J9
AAYXX
ABBLG
ABJNI
ABLBI
ABQRX
ADHLV
AHGAQ
BAANH
CITATION
CUPRZ
GGK
ID FETCH-LOGICAL-a277t-4402b75de5da39aff7ca12e29c1ab4b787220a89e7de0f29cf5d424bcebd6e0f3
IEDL.DBID ACS
ISSN 1528-7483
IngestDate Tue Jul 01 02:26:22 EDT 2025
Thu Apr 24 23:00:41 EDT 2025
Fri Feb 05 20:53:56 EST 2021
IsPeerReviewed true
IsScholarly true
Issue 2
Language English
License https://doi.org/10.15223/policy-029
https://doi.org/10.15223/policy-037
https://doi.org/10.15223/policy-045
LinkModel DirectLink
MergedId FETCHMERGED-LOGICAL-a277t-4402b75de5da39aff7ca12e29c1ab4b787220a89e7de0f29cf5d424bcebd6e0f3
ORCID 0000-0002-6087-4880
0000-0002-3959-901X
PageCount 9
ParticipantIDs crossref_citationtrail_10_1021_acs_cgd_0c01153
crossref_primary_10_1021_acs_cgd_0c01153
acs_journals_10_1021_acs_cgd_0c01153
ProviderPackageCode JG~
55A
AABXI
GNL
VF5
7~N
VG9
W1F
ACS
AEESW
AFEFF
ABMVS
ABUCX
IH9
AQSVZ
ED~
UI2
CITATION
AAYXX
PublicationCentury 2000
PublicationDate 20210203
2021-02-03
PublicationDateYYYYMMDD 2021-02-03
PublicationDate_xml – month: 02
  year: 2021
  text: 20210203
  day: 03
PublicationDecade 2020
PublicationTitle Crystal growth & design
PublicationTitleAlternate Cryst. Growth Des
PublicationYear 2021
Publisher American Chemical Society
Publisher_xml – name: American Chemical Society
References ref9/cit9
ref45/cit45
ref3/cit3
ref27/cit27
ref16/cit16
ref23/cit23
ref8/cit8
ref31/cit31
ref2/cit2
ref37/cit37
ref20/cit20
ref48/cit48
ref17/cit17
ref10/cit10
ref35/cit35
ref19/cit19
ref21/cit21
ref42/cit42
ref46/cit46
ref49/cit49
ref13/cit13
ref24/cit24
ref38/cit38
ref50/cit50
ref6/cit6
ref36/cit36
ref18/cit18
ref11/cit11
ref25/cit25
ref29/cit29
ref32/cit32
ref39/cit39
ref14/cit14
ref5/cit5
ref43/cit43
ref28/cit28
ref40/cit40
Hiendrawan S. (ref34/cit34) 2015; 7
ref26/cit26
ref12/cit12
ref15/cit15
ref41/cit41
ref22/cit22
ref33/cit33
ref4/cit4
ref30/cit30
ref47/cit47
ref1/cit1
ref44/cit44
ref7/cit7
References_xml – ident: ref4/cit4
  doi: 10.1021/cg300327x
– ident: ref13/cit13
  doi: 10.1021/bi00197a003
– ident: ref6/cit6
  doi: 10.1016/j.ijpharm.2015.12.001
– ident: ref50/cit50
  doi: 10.1163/016942410X525678
– ident: ref28/cit28
  doi: 10.1021/acs.cgd.6b01769
– ident: ref12/cit12
  doi: 10.1016/S0305-7372(97)90019-0
– ident: ref2/cit2
  doi: 10.1016/j.ijpharm.2012.10.043
– ident: ref46/cit46
  doi: 10.1021/cg5018642
– ident: ref16/cit16
  doi: 10.1021/cg400322t
– ident: ref49/cit49
  doi: 10.1002/jps.21552
– ident: ref38/cit38
  doi: 10.1007/s11095-007-9394-1
– ident: ref18/cit18
  doi: 10.1021/acs.cgd.8b00807
– ident: ref20/cit20
  doi: 10.1016/j.jpba.2019.05.035
– ident: ref10/cit10
  doi: 10.1039/C5CC08216A
– ident: ref23/cit23
  doi: 10.1007/s11060-015-1804-3
– ident: ref40/cit40
– volume: 7
  start-page: 160
  year: 2015
  ident: ref34/cit34
  publication-title: Int. J. Pharm. Pharm. Sci.
– ident: ref42/cit42
  doi: 10.1039/c2ce25724f
– ident: ref29/cit29
  doi: 10.1002/asia.200800070
– ident: ref21/cit21
  doi: 10.4103/0253-7613.115015
– ident: ref7/cit7
  doi: 10.1016/j.ejps.2015.10.006
– ident: ref26/cit26
  doi: 10.1016/j.lwt.2018.04.056
– ident: ref1/cit1
  doi: 10.1021/cg3002948
– ident: ref8/cit8
  doi: 10.1016/j.drudis.2016.02.001
– ident: ref19/cit19
  doi: 10.1016/j.ejps.2018.12.006
– ident: ref43/cit43
  doi: 10.1021/acs.cgd.0c00326
– ident: ref25/cit25
  doi: 10.1016/j.tiv.2013.12.002
– ident: ref33/cit33
  doi: 10.1016/j.molstruc.2008.11.037
– ident: ref48/cit48
  doi: 10.1002/jps.20262
– ident: ref41/cit41
  doi: 10.1021/cg500327s
– ident: ref36/cit36
  doi: 10.1016/j.jff.2013.05.006
– ident: ref11/cit11
  doi: 10.18632/oncotarget.17401
– ident: ref47/cit47
  doi: 10.1023/A:1011954800246
– ident: ref30/cit30
  doi: 10.1021/jm00096a013
– ident: ref22/cit22
  doi: 10.1017/S0007114510003910
– ident: ref44/cit44
  doi: 10.1248/bpb.32.671
– ident: ref5/cit5
  doi: 10.1016/j.ejps.2017.04.008
– ident: ref45/cit45
  doi: 10.1039/c000614a
– ident: ref9/cit9
  doi: 10.3390/cryst8020101
– ident: ref14/cit14
  doi: 10.1093/neuonc/noy072
– ident: ref15/cit15
  doi: 10.1002/asia.201200205
– ident: ref24/cit24
  doi: 10.1080/01635581.2019.1638424
– ident: ref32/cit32
  doi: 10.1248/cpb.42.1143
– ident: ref31/cit31
  doi: 10.1107/S0108270187089510
– ident: ref27/cit27
  doi: 10.1016/j.lwt.2019.03.059
– ident: ref35/cit35
  doi: 10.1021/cg200704s
– ident: ref3/cit3
  doi: 10.1016/j.tips.2012.12.003
– ident: ref37/cit37
  doi: 10.3390/molecules181215344
– ident: ref17/cit17
  doi: 10.1007/s40010-014-0142-8
– ident: ref39/cit39
  doi: 10.1166/asl.2017.8486
SSID ssj0007633
Score 2.5820239
Snippet A new 1:1 drug–drug cocrystal of temozolomide and hesperetin was successfully prepared by liquid-assisted grinding, slurry conversion crystallization, and...
SourceID crossref
acs
SourceType Enrichment Source
Index Database
Publisher
StartPage 838
Title Temozolomide–Hesperetin Drug–Drug Cocrystal with Optimized Performance in Stability, Dissolution, and Tabletability
URI http://dx.doi.org/10.1021/acs.cgd.0c01153
Volume 21
hasFullText 1
inHoldings 1
isFullTextHit
isPrint
link http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwjV3JTsMwELWgHIADSwFRNvnQA4emJI4TJ0fUUlVILBKt1FvkLaiiC2pTofbEP_CHfAnjNF1EVcEp0iSOrLHHfvY8PyNUjG1FGKfK0pQpi0rCrDCIPUt7KoBls2-rNKP78OjXm_S-5bUWYtG_M_jEueESnP-qyrY06MXdRFvEhxA2KKjyMh90IUxSLr1HUnlMd67is_IDMw3J4dI0tDSf1PanTKxhKkNoaCRv5VEiynKyKtL4d1UP0F6GKvHttBscog3dy6PtyuwytzzaXdIdPEIfDd3tT2DY67aV_v78qmujF24OP-PqYPQKFvPAlb4cjAE9drDZrcVPMLp02xOt8PPitAGGMgBYU4rtuISr7XlnLmHeU7hhjmbN3h-jZu2uUalb2Q0MFieMJRaF1aVgnoKW427I45hJ7hBNQulwQQUEOyE2D0LNlLZjMMeeooQKqYXyweKeoFyv39OnCPtUOBrAMXeCgHIheaDsOFaSBb4hQpMCKoL7oiyChlGaHCdOZIzg0yjzaQGVZ-0WyUzF3Fym0Vlf4Hpe4H0q4LHu07P_VeEc7RBDbDHUbfcC5ZLBSF8CMknEVdonfwAsvuK5
linkProvider American Chemical Society
linkToHtml http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwlV3JTsMwEB0VOAAHdsSODxw4kJI4TpweUaEqUDZRJG6Rt6AK2qIuQvTEP_CHfAnjkKYVCAlOkSaxNbJn7Od45g3AXuJqygXTjmFcO0xR7pSiJHBMoCM8NoeuTm90Ly7D6h07uw_uC-AOc2FQiS721E0v8UfsAt6hlakHXXSVBTH-BEwhFKHWpo_Kt_nai96ShtQHNGXJ9HMynx8d2N1Idcd2o7FtpTIPN7lCaTTJY7Hfk0U1-MbV-B-NF2Auw5jk6MsoFqFgWkswXR6WdluC2TEWwmV4qZtme4CLYLOhzcfbe9VY9nCbCk2OO_0HlNgHKbdV5xWx5BOx_27JFa41zcbAaHI9yj0g2Abhaxpw-3pAjhu5aR8Q0dKkbhO1hu9X4K5yUi9XnawegyMo5z2H4VlT8kDjPAq_JJKEK-FRQ0vKE5JJdH1KXRGVDNfGTVCcBJpRJpWROkSJvwqTrXbLrAEJmfQMQmXhRRETUolIu0miFY9CGxZN12EPhy_O_Kkbp1fl1IutEMc0zsZ0HYrD6YtVxmluS2s8_d5gP2_w_EXn8dunG39TYRemq_WLWlw7vTzfhBlqQ15sULe_BZO9Tt9sI2bpyZ3UTD8BpCLrGg
linkToPdf http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwlV3NTttAEB61VCpwoC20gkLpHjhwwKm9XnudI0qIUtpSpCYSN2t_o6gkQfkRIqe-A2_IkzBjHBO1QqInS2PParQ7MzvrmfkW4MCHlkslbOCEtIEwXAb1zCeBS2yGx-Y0tEVG98dZ2u6K04vkomwKo14YFGKCI02KJD5Z9ZX1JcJA9IXopmdroaFAJn4JryhpR3p93PhV-V-0mKKsPuEFUmZcAfr8MwDtSGaytCMtbS2tN9CthCoqSn7XZlNdM_O_8Br_V-q3sFHGmuz4QTnewQs33ITVxuKKt01YX0Ij3ILrjhuM5ugMB33r7v7cth2hiFNLNGuOZz2k0IM1RmZ8gzHlJaN_uOwn-pxBf-4sO3_sQWDIg2FsUXh7c8Sa_UrFj5gaWtahhq3F-_fQbZ10Gu2gvJchUFzKaSDwzKllYnE9VVxX3kujIu543URKC40ugPNQZXUnrQs9kn1iBRfaOG1TpMQfYGU4GrptYKnQkcOQWUVZJpQ2KrOh99bILKXyaL4DBzh9eWlXk7xImfMoJyLOaV7O6Q7UFkuYmxLbnK7YuHya4bBiuHqA9Xjq04_PE-EzvD5vtvLvX8--7cIap8oXqu2O92BlOp65Txi6TPV-oan3K4rtnQ
openUrl ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Temozolomide%E2%80%93Hesperetin+Drug%E2%80%93Drug+Cocrystal+with+Optimized+Performance+in+Stability%2C+Dissolution%2C+and+Tabletability&rft.jtitle=Crystal+growth+%26+design&rft.au=Wang%2C+Jie&rft.au=Dai%2C+Xia-Lin&rft.au=Lu%2C+Tong-Bu&rft.au=Chen%2C+Jia-Mei&rft.date=2021-02-03&rft.issn=1528-7483&rft.eissn=1528-7505&rft.volume=21&rft.issue=2&rft.spage=838&rft.epage=846&rft_id=info:doi/10.1021%2Facs.cgd.0c01153&rft.externalDBID=n%2Fa&rft.externalDocID=10_1021_acs_cgd_0c01153
thumbnail_l http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=1528-7483&client=summon
thumbnail_m http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=1528-7483&client=summon
thumbnail_s http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=1528-7483&client=summon