a new polymorph of the dimer of thioimidazole was described in details by a
combined use of XRD, quantum chemical calculations, and Raman spectroscopy.
These studies reveal a fascinating crystal architecture, where four nonequivalent
molecules are present in the unit cell, which exhaust the existing conformers of the
isolated molecule of the compound.
The electronic and geometric major features of the hydantoin moiety were
described, leading to the very interesting picture of reciprocal influence of the r and
p electronic systems (through p electron charge donation from the nitrogen atoms to
the carbonyl oxygens and r backdonation from these latter to the ring), which
determine the details of the geometries of the studied molecules and, ultimately,
also determine their photofragmentation pattern, which takes place by cleavage of
the weakest bonds in the ring and keeping intact the fragment (OCNH) constituted
by the strongest (shorter) bonds of the hydantoin ring. Polymorphism shown by the
hydantoins has been studied, and several new polymorphs are identified for 1MH,
5MH, and AAH. For 1MH, an unusual transformation between the two polymorphs of the compound which takes place in keeping crystal integrity was
observed. For AAH, an intriguing case of conformational selection where the
highest energy conformer for the isolated molecule situation (higher in energy than
the most stable conformer by ca. 40 kJ mol
−1 ) is chosen to form a crystal was
described.
Acknowledgements This investigation has been performed within the Project PTDC/QEQ-QFI/
3284/2014–POCI-01-0145-FEDER-016617, funded by the Portuguese “Fundação para a Ciência
e a Tecnologia” (FCT) and FEDER/COMPETE 2020-EU. The Coimbra Chemistry Centre
(CQC) is supported by FCT, through the project UI0313/QUI/2013, also cofunded by FEDER/
COMPETE 2020-EU. E.M.B. and B.A.N. thank FCT for the grant CCMAR/BI/0013/2017, within
Project PTDC/MAR-BIO/4132/2014, and the Ph.D. grant SFRH/BD/129852/2017, respectively.
R.F. and G.O.I. acknowledge the financial support through the project MATIS–Materiais e
Tecnologias Industriais Sustentáveis (FCT and CENTRO-01-0145-FEDER-000014).
References
1. Whittle E, Dows DA, Pimentel GC (1954) Matrix isolation method for the experimental study
of unstable species. J Chem Phys 22:1943–1944
2. Norman I, Porter G (1954) Trapped atoms and radicals in a glass ‘cage’. Nature 174:508–509
3. Holler TP, Ruan F, Spaltenstein A, Hopkins PB (1989) Total synthesis of marine
mercaptohistidines: ovothiols A, B, and C. J Org Chem 54:4570–4575
4. Hand CE, Honek JF (2005) Biological chemistry of naturally occurring thiols of microbial
and marine origin. J Nat Prod 68:293–308
5. Zoete V, Vezin H, Bailly F, Vergoten G, Catteau J-P, Bernier J-L (2000)
4-mercaptoimidazoles derived from the naturally occurring antioxidant ovothiols 2.
Computational and experimental approach of the radical scavenging mechanism. Free Rad
Res 32:525–533
6. Crépin A, Wattier N, Petit S, Bischoff L, Fruit C, Marsais F (2009) Aminoacid-derived
mercaptoimidazoles. Org Biomol Chem 7:128–134
220
R. Fausto et al.
combined use of XRD, quantum chemical calculations, and Raman spectroscopy.
These studies reveal a fascinating crystal architecture, where four nonequivalent
molecules are present in the unit cell, which exhaust the existing conformers of the
isolated molecule of the compound.
The electronic and geometric major features of the hydantoin moiety were
described, leading to the very interesting picture of reciprocal influence of the r and
p electronic systems (through p electron charge donation from the nitrogen atoms to
the carbonyl oxygens and r backdonation from these latter to the ring), which
determine the details of the geometries of the studied molecules and, ultimately,
also determine their photofragmentation pattern, which takes place by cleavage of
the weakest bonds in the ring and keeping intact the fragment (OCNH) constituted
by the strongest (shorter) bonds of the hydantoin ring. Polymorphism shown by the
hydantoins has been studied, and several new polymorphs are identified for 1MH,
5MH, and AAH. For 1MH, an unusual transformation between the two polymorphs of the compound which takes place in keeping crystal integrity was
observed. For AAH, an intriguing case of conformational selection where the
highest energy conformer for the isolated molecule situation (higher in energy than
the most stable conformer by ca. 40 kJ mol
−1 ) is chosen to form a crystal was
described.
Acknowledgements This investigation has been performed within the Project PTDC/QEQ-QFI/
3284/2014–POCI-01-0145-FEDER-016617, funded by the Portuguese “Fundação para a Ciência
e a Tecnologia” (FCT) and FEDER/COMPETE 2020-EU. The Coimbra Chemistry Centre
(CQC) is supported by FCT, through the project UI0313/QUI/2013, also cofunded by FEDER/
COMPETE 2020-EU. E.M.B. and B.A.N. thank FCT for the grant CCMAR/BI/0013/2017, within
Project PTDC/MAR-BIO/4132/2014, and the Ph.D. grant SFRH/BD/129852/2017, respectively.
R.F. and G.O.I. acknowledge the financial support through the project MATIS–Materiais e
Tecnologias Industriais Sustentáveis (FCT and CENTRO-01-0145-FEDER-000014).
References
1. Whittle E, Dows DA, Pimentel GC (1954) Matrix isolation method for the experimental study
of unstable species. J Chem Phys 22:1943–1944
2. Norman I, Porter G (1954) Trapped atoms and radicals in a glass ‘cage’. Nature 174:508–509
3. Holler TP, Ruan F, Spaltenstein A, Hopkins PB (1989) Total synthesis of marine
mercaptohistidines: ovothiols A, B, and C. J Org Chem 54:4570–4575
4. Hand CE, Honek JF (2005) Biological chemistry of naturally occurring thiols of microbial
and marine origin. J Nat Prod 68:293–308
5. Zoete V, Vezin H, Bailly F, Vergoten G, Catteau J-P, Bernier J-L (2000)
4-mercaptoimidazoles derived from the naturally occurring antioxidant ovothiols 2.
Computational and experimental approach of the radical scavenging mechanism. Free Rad
Res 32:525–533
6. Crépin A, Wattier N, Petit S, Bischoff L, Fruit C, Marsais F (2009) Aminoacid-derived
mercaptoimidazoles. Org Biomol Chem 7:128–134
220
R. Fausto et al.