TY - JOUR
T1 - Mechanochemical synthesis and structure of the tetrahydrate and mesoporous anhydrous metforminium(2+)-n,n0-1,4-phenylenedioxalamic acid (1:2) salt: The role of hydrogen bonding and n→ π charge assisted interactions
T2 - The role of hydrogen bonding and n→ π charge assisted interactions
AU - Chong-Canto, Sayuri
AU - García-Báez, Efrén V.
AU - Martínez-Martínez, Francisco J.
AU - Ramos-Organillo, Angel A.
AU - Padilla-Martínez, Itzia I.
N1 - Funding Information:
Funding: This research was funded by CONACYT, grant number 255354 and Secretaría de Investigación y Posgrado del Instituto Politécnico Nacional, grant number 20170504.
Funding Information:
Acknowledgments: This work was supported by CONACYT Grant 255354, SIP-IPN Grant 20170504 (Secretaria de Investigación y Posgrado del Instituto Politécnico Nacional), CONACYT’ “Red Tematica de Química Supramolecular” Grant 271884. CGIC-UC (Coordinación General de Investigacioón Científica de la Universidad de Colima) and PROMEP-SEP. S.C.-C. thanks CONACYT for fellowship and I.I.P.-M. Thanks Susana Rojas-Lima of UAEH for the access to the X-ray diffractometer.
Funding Information:
This research was funded by CONACYT, grant number 255354 and Secretar?a de Investigaci?n y Posgrado del Instituto Polit?cnico Nacional, grant number 20170504.
Publisher Copyright:
© 2020 by the authors.
PY - 2020/10
Y1 - 2020/10
N2 - A new organic salt of metformin, an antidiabetic drug, and N,N0-(1,4-phenylene)dioxalamic acid, was mechanochemically synthesized, purified by crystallization from solution and characterized by single X-ray crystallography. The structure revealed a salt-type crystal hydrate composed of one dicationic metformin unit, two monoanionic units of the acid and four water molecules, namely H2Mf(HpOXA)2 4H2O. X-ray powder, IR,13C-CPMAS, thermal and BET adsorption–desorption analyses were performed to elucidate the structure of the molecular and supramolecular structure of the anhydrous microcrystalline mesoporous solid H2Mf(HpOXA)2. The results suggest that their structures, conformation and hydrogen bonding schemes are very similar. To the best of our knowledge, the selective formation of the monoanion HpOXA-, as well as its structure in the solid, is herein reported for the first time. Regular O(δ-)···C(δ), O(δ-)···N+ and bifacial O(δ-)···C(δ) ···O(δ-) of n→π* charge-assisted interactions are herein described in H2MfA organic salts which could be responsible of the interactions of metformin in biologic systems. The results support the participation of n→π * charge-assisted interactions independently, and not just as a short contact imposed by the geometric constraint due to the hydrogen bonding patterns.
AB - A new organic salt of metformin, an antidiabetic drug, and N,N0-(1,4-phenylene)dioxalamic acid, was mechanochemically synthesized, purified by crystallization from solution and characterized by single X-ray crystallography. The structure revealed a salt-type crystal hydrate composed of one dicationic metformin unit, two monoanionic units of the acid and four water molecules, namely H2Mf(HpOXA)2 4H2O. X-ray powder, IR,13C-CPMAS, thermal and BET adsorption–desorption analyses were performed to elucidate the structure of the molecular and supramolecular structure of the anhydrous microcrystalline mesoporous solid H2Mf(HpOXA)2. The results suggest that their structures, conformation and hydrogen bonding schemes are very similar. To the best of our knowledge, the selective formation of the monoanion HpOXA-, as well as its structure in the solid, is herein reported for the first time. Regular O(δ-)···C(δ), O(δ-)···N+ and bifacial O(δ-)···C(δ) ···O(δ-) of n→π* charge-assisted interactions are herein described in H2MfA organic salts which could be responsible of the interactions of metformin in biologic systems. The results support the participation of n→π * charge-assisted interactions independently, and not just as a short contact imposed by the geometric constraint due to the hydrogen bonding patterns.
KW - Dicationic metformin
KW - Mechanochemical synthesis
KW - Mesoporous anhydrate
KW - Metformin cocrystal
KW - Pi-interactions
KW - Water channels
UR - http://www.scopus.com/inward/record.url?scp=85094616807&partnerID=8YFLogxK
U2 - 10.3390/pharmaceutics12100998
DO - 10.3390/pharmaceutics12100998
M3 - Artículo
C2 - 33096739
AN - SCOPUS:85094616807
VL - 12
SP - 1
EP - 16
JO - Pharmaceutics
JF - Pharmaceutics
IS - 10
M1 - 998
ER -