computer aided design of molecular recognition agents
DESCRIPTION
Ongoing research at the laboratory of Dr. Joaquín Barroso at the National Autonomous University of Mexico on molecular recognition agents through careful design and tailoring of the electron density in calixarene cavitands.TRANSCRIPT
![Page 1: Computer Aided Design of Molecular Recognition Agents](https://reader030.vdocument.in/reader030/viewer/2022020218/5597631d1a28abe0778b47c5/html5/thumbnails/1.jpg)
Diseño in silico de Agentes de Reconocimiento Molecular
Dr. Joaquín Barroso Flores
Centro Conjunto de Investigación en Química Sustentable
![Page 2: Computer Aided Design of Molecular Recognition Agents](https://reader030.vdocument.in/reader030/viewer/2022020218/5597631d1a28abe0778b47c5/html5/thumbnails/2.jpg)
J. Phys. Chem. B, 2011, 115, 8797Proc. Natl. Acad. Sci., 1998, 9280Nature Medicine, 2011, 1206
-Acetilcolinacolinesterasa -Chaperonina
El recnoncimiento molecular es ubicuo en bioquímica
![Page 3: Computer Aided Design of Molecular Recognition Agents](https://reader030.vdocument.in/reader030/viewer/2022020218/5597631d1a28abe0778b47c5/html5/thumbnails/3.jpg)
Reconocimiento molecular escomplementariedad molecular
• Complementariedad estérica
• Complementariedad química
• Complementariedad de densidad electrónica
• Interacciones no covalentes
![Page 4: Computer Aided Design of Molecular Recognition Agents](https://reader030.vdocument.in/reader030/viewer/2022020218/5597631d1a28abe0778b47c5/html5/thumbnails/4.jpg)
calix[n]arenos como agentes de recnonocimiento
Vicens, J., Harrowfield, J., & Baklouti, L. (Eds.). (2007). Calixarenes in the Nanoworld. Springer Netherlands. doi:10.1007/978-1-4020-5022-4
![Page 5: Computer Aided Design of Molecular Recognition Agents](https://reader030.vdocument.in/reader030/viewer/2022020218/5597631d1a28abe0778b47c5/html5/thumbnails/5.jpg)
Las posibilidades son inmensas
Sayin, S.; Ozcan, F.; Yilmaz, M. Mater. Sci. Eng. C. Mater. Biol. Appl.2013, 33, 2433–9.
Akceylan, E.; Yilmaz, M. J. Macromol. Sci. Part A 2012, 49, 911–917.
Perret, F.; Coleman, A. W. Chem. Commun. (Camb). 2011, 47, 7303–19.
M. Mourer, N. Psychogios, G. Laumond, A.-M. Aubertin,J.-B. Regnouf-de-Vains, Bioorg. Med. Chem., 2010, 18, 36–45.
![Page 6: Computer Aided Design of Molecular Recognition Agents](https://reader030.vdocument.in/reader030/viewer/2022020218/5597631d1a28abe0778b47c5/html5/thumbnails/6.jpg)
calix[n]arenos como agentes de reconocimiento
Cono Cono parcial
1,3-alternado 1,2-alternado
A mayor n mayor flexibilidad.
Adaptabilidad al ‘campo molecular’ de un sustrato
![Page 7: Computer Aided Design of Molecular Recognition Agents](https://reader030.vdocument.in/reader030/viewer/2022020218/5597631d1a28abe0778b47c5/html5/thumbnails/7.jpg)
ACARREADORES DE FÁRMACOS
![Page 8: Computer Aided Design of Molecular Recognition Agents](https://reader030.vdocument.in/reader030/viewer/2022020218/5597631d1a28abe0778b47c5/html5/thumbnails/8.jpg)
Sistemas transportadores
de fármacos
Hong, R. et al. JACS (2006) 128 (4) 1078-1079
Adair. J. et al. ACS Nano(2010) 4 (9) 4967-4970
Nanopartículas
Liposomas
Du, J. et al. Mol. Pharmaceutics(2009) 6 (3) 905-917
Micelas
Lee, J. et al. Mol. Pharmaceutics (2007) 4 (5) 769-781
Dendrímeros
Paleos, C. Mol. Pharmaceutics (2007) 4 (2) 169-188
![Page 9: Computer Aided Design of Molecular Recognition Agents](https://reader030.vdocument.in/reader030/viewer/2022020218/5597631d1a28abe0778b47c5/html5/thumbnails/9.jpg)
Acarreadores Monomoleculares
Masson, et al. RSC Adv. (2012) 2, 1213-1247
Freeman, Acta Crystallogr. B. (1984) 382-387
CucurbiturilosCiclodextrinas
Horvath, G. et al. , Mol. pharmaceutics. (2008) 5 (2) 358-363
![Page 10: Computer Aided Design of Molecular Recognition Agents](https://reader030.vdocument.in/reader030/viewer/2022020218/5597631d1a28abe0778b47c5/html5/thumbnails/10.jpg)
Grupos hidrofílicos
Grupos hidrofílicos
• Oligosacáridos• No tóxicos• Degradables• Hidrofílicos
Ciclodextrinas
RígidosPoco funcionalizablesPoco selectivosDifíciles de sintetizar
![Page 11: Computer Aided Design of Molecular Recognition Agents](https://reader030.vdocument.in/reader030/viewer/2022020218/5597631d1a28abe0778b47c5/html5/thumbnails/11.jpg)
Leucemia Mieloide CrónicaImatinib (Gleevec, Novartis)
Inhibidor de Tirosín cinasas III
Nagar, B. et al. Crystal Structure of the C-ABL kinasedomaine in complex with sti-571 (2001)
N
N
HN
O
HN
N
N
N
Biodisponibilidad ~90%Unión a proteínas ~95%
Efectos secundarios: Edema, irritación, fallo cardiaco*
![Page 12: Computer Aided Design of Molecular Recognition Agents](https://reader030.vdocument.in/reader030/viewer/2022020218/5597631d1a28abe0778b47c5/html5/thumbnails/12.jpg)
Espacio de parámetros estructurales
18 calix[n]arenos
18 tia-calix[n]arenos
36 Anfitriones
![Page 13: Computer Aided Design of Molecular Recognition Agents](https://reader030.vdocument.in/reader030/viewer/2022020218/5597631d1a28abe0778b47c5/html5/thumbnails/13.jpg)
Complejos de inclusión(host-guest)
tia-calix[8]aren-octaetanoilo
(Vista lateral)
(Vista superior)
N1N2
![Page 14: Computer Aided Design of Molecular Recognition Agents](https://reader030.vdocument.in/reader030/viewer/2022020218/5597631d1a28abe0778b47c5/html5/thumbnails/14.jpg)
Galindo-murillo, R.; Sandoval-Salinas, M. E.; Barroso-Flores, J. (2014) J. Chem. Theory Comp. DOI: 10.1021/ct4004178
Eint > 46 kcal/mol (2.0 eV)B97D/6-31G+(d,p)
QM)-Optimización geométrica-Análisis poblacional NBO-Energía Interacción NBODel
=B97D/6-31G+(d,p)=MD)-(GAFF)PMF + US
![Page 15: Computer Aided Design of Molecular Recognition Agents](https://reader030.vdocument.in/reader030/viewer/2022020218/5597631d1a28abe0778b47c5/html5/thumbnails/15.jpg)
Conformaciones obtenidas pordinámica molecular (GAFF, +100ns)
A) Fármaco permanece en la cavidad (pseudo-rotaxano) (1s5)@N2
B) Se conserva la interacción (liberación parcial) (6c5)@N1
C) Fármaco liberado (interacción externa) (3s6)@N1
![Page 16: Computer Aided Design of Molecular Recognition Agents](https://reader030.vdocument.in/reader030/viewer/2022020218/5597631d1a28abe0778b47c5/html5/thumbnails/16.jpg)
PMF (DM) +100ns
N1(piridina)
N2(piperazina)
Galindo-murillo, R.; Sandoval-Salinas, M. E.; Barroso-Flores, J. (2014) J. Chem. Theory Comp. DOI: 10.1021/ct4004178
![Page 17: Computer Aided Design of Molecular Recognition Agents](https://reader030.vdocument.in/reader030/viewer/2022020218/5597631d1a28abe0778b47c5/html5/thumbnails/17.jpg)
N
HN
O
O
HN
HN
O
FF
F
Cl
N
N
HN
O
HN
N
N
N
Imatinib
Inhibidores de Tirosín Cinasas III, 2a generación (CML resistente a Imatinib)
Cl Cl
O NH
N
N
O
O N
N
Bosutinib Sorafenib
![Page 18: Computer Aided Design of Molecular Recognition Agents](https://reader030.vdocument.in/reader030/viewer/2022020218/5597631d1a28abe0778b47c5/html5/thumbnails/18.jpg)
Algunas versiones de bosutinib son isómeros erroneos
Cl Cl
O NH
N
N
O
O N
N
O
Cl NH
N
N
O
O N
N
Cl
Levinson, N. M., & Boxer, S. G. (2012). PloS One, 7(4), e29828. doi:10.1371/journal.pone.0029828
Bosutinib pseudo-Bosutinib
![Page 19: Computer Aided Design of Molecular Recognition Agents](https://reader030.vdocument.in/reader030/viewer/2022020218/5597631d1a28abe0778b47c5/html5/thumbnails/19.jpg)
Nuestros agentes tienen el potencialde discriminar entre isómeros
Puentes de halógeno* Y-O…Cl (Y = C; P; S)
Las vibraciones C-Cl se desplazarán a menoresfrecuencias con la interacción Y-O…Cl
Auffinger, P., Hays, F. a, Westhof, E., & Ho, P. S. (2004). Halogen bonds in biological molecules. Proceedings of the National Academy of Sciences of the United States of America, 101(48), 16789–94. doi:10.1073/pnas.0407607101
B97D/6-31+G(d,p)IEW CO--Cl 10-2
![Page 20: Computer Aided Design of Molecular Recognition Agents](https://reader030.vdocument.in/reader030/viewer/2022020218/5597631d1a28abe0778b47c5/html5/thumbnails/20.jpg)
Cardiotoxicidad del Imatinib
• Posiblemente ligada a muerte celular por ERS y/o OS en mitocondrias (interacción con Quinasas c-Jun N-terminales2 o PARP3)
• Sorafenib y Bosutinibson menos tóxicos pero menos eficientes
• Gefitinib y Erlotinib no son tóxicos
1Kerkelä R, et al. (2006). Nat. Med. 12(8):908–9162Sarszegi, Z., et al. (2012). Mol. Cell. Biochem., 365(1-2), 129–37. doi:10.1007/s11010-012-1252-83Moehring A, et al. (2005). Cell Death Differ 12:627–636
c-Jun N-terminal quinasa / inhibidor similar a IMB
Gray et al. Chem. Biol. (2012) 19: 140-154
![Page 21: Computer Aided Design of Molecular Recognition Agents](https://reader030.vdocument.in/reader030/viewer/2022020218/5597631d1a28abe0778b47c5/html5/thumbnails/21.jpg)
Complejos de inclusión previenen la interacción
Quinasa C-Jun N terminal tomada de Gray et al. Chem. Biol. (2012) 19: 140-154
![Page 22: Computer Aided Design of Molecular Recognition Agents](https://reader030.vdocument.in/reader030/viewer/2022020218/5597631d1a28abe0778b47c5/html5/thumbnails/22.jpg)
GTP se une a otros dominios de TC
Murata, K., et al. (2003). J. Biological Chem., 278(85), 32892-8. doi:10.1074/jbc.M210405200
R = SO3H; OEtn = 4, 5, 6, 8
B97D/6-31+G(d,p)
![Page 23: Computer Aided Design of Molecular Recognition Agents](https://reader030.vdocument.in/reader030/viewer/2022020218/5597631d1a28abe0778b47c5/html5/thumbnails/23.jpg)
Eint calix - GTP
Olmedo-Romero A.; Cruz-Flores, E.; Barroso-Flores, J. (2014) Comp. Theor. Chem. En revisión
B97D/6-31+G(d,p)
![Page 24: Computer Aided Design of Molecular Recognition Agents](https://reader030.vdocument.in/reader030/viewer/2022020218/5597631d1a28abe0778b47c5/html5/thumbnails/24.jpg)
Eint calix - GTP
Olmedo-Romero A.; Cruz-Flores, E.; Barroso-Flores, J. (2014) Comp. Theor. Chem. En revisión
B97D/6-31+G(d,p)
![Page 25: Computer Aided Design of Molecular Recognition Agents](https://reader030.vdocument.in/reader030/viewer/2022020218/5597631d1a28abe0778b47c5/html5/thumbnails/25.jpg)
Dinámica molecular
(GAFF/TIP3P +100ns)
![Page 26: Computer Aided Design of Molecular Recognition Agents](https://reader030.vdocument.in/reader030/viewer/2022020218/5597631d1a28abe0778b47c5/html5/thumbnails/26.jpg)
EXTRACCIÓN DE ESPECIESINORGÁNICAS
![Page 27: Computer Aided Design of Molecular Recognition Agents](https://reader030.vdocument.in/reader030/viewer/2022020218/5597631d1a28abe0778b47c5/html5/thumbnails/27.jpg)
Interacciones catión - π
Barroso-Flores, J., Silaghi-Dumitrescu, I., Petrar, P. M., & Kunsági-Máté, S. (2013). J. Inclusion Phen. Macrocyclic Chem., 75(1-2), 39–46. doi:10.1007/s10847-012-0144-6
Li+ Na+ Cs+
Ca2+ Ba2+
Ion Eint cmplx kcal/mol Eint calix kcal/mol % cambio
Li+ 2.80 3.71 32.2
Na+ 4.05 4.99 23.1
Cs+ 10.88 11.37 4.5
NBODel(30.72 kcal/mol)
![Page 28: Computer Aided Design of Molecular Recognition Agents](https://reader030.vdocument.in/reader030/viewer/2022020218/5597631d1a28abe0778b47c5/html5/thumbnails/28.jpg)
Interacciones catión - π
Li+ Na+ Cs+ Ca2+ Ba2+
0.065 0.101 0.0007 0.063 0.046
![Page 29: Computer Aided Design of Molecular Recognition Agents](https://reader030.vdocument.in/reader030/viewer/2022020218/5597631d1a28abe0778b47c5/html5/thumbnails/29.jpg)
Complejos calix – iones
Yoneyama, T.; Sadamatsu, H.; Kuwata, S.; Kawakita, H.; Ohto, K. Talanta 2012, 88, 121–8.
Kamboh, M. A.; Yilmaz, M. Desalination 2013, 310, 67–74.
Varnek, A.; Wipff, G. J. Comput. Chem. 1996, 17, 1520–1531.
Kiegiel, K.; Steczek, L.; Zakrzewska-trznadel, G. J. Chem. 2013. 10.1155/2013/762819
Qureshi, I.; Memon, S.; Yilmaz, CLEAN - Soil, Air, Water 2013, 41, 258–266.
Kulesza, J.; Bocheńska, M. Eur. J. Inorg. Chem.2011, 2011, 777–783.
![Page 30: Computer Aided Design of Molecular Recognition Agents](https://reader030.vdocument.in/reader030/viewer/2022020218/5597631d1a28abe0778b47c5/html5/thumbnails/30.jpg)
Calix[4]-Pb2+
t-bu i-pr COOH
(CH2)2NH2(CH2)2OH SO3H
B97D/6-31+G(d,p);LANL2DZ(Pb)
![Page 31: Computer Aided Design of Molecular Recognition Agents](https://reader030.vdocument.in/reader030/viewer/2022020218/5597631d1a28abe0778b47c5/html5/thumbnails/31.jpg)
Calix[5]-Pb2+
t-bu i-pr COOH
(CH2)2NH2(CH2)2OH SO3H
B97D/6-31+G(d,p);LANL2DZ(Pb)
![Page 32: Computer Aided Design of Molecular Recognition Agents](https://reader030.vdocument.in/reader030/viewer/2022020218/5597631d1a28abe0778b47c5/html5/thumbnails/32.jpg)
Calix[6]-Pb2+
t-bu i-pr COOH
(CH2)2NH2 (CH2)2OH SO3H
B97D/6-31+G(d,p);LANL2DZ(Pb)
![Page 33: Computer Aided Design of Molecular Recognition Agents](https://reader030.vdocument.in/reader030/viewer/2022020218/5597631d1a28abe0778b47c5/html5/thumbnails/33.jpg)
Calix[5]-Hg2+
t-bu i-pr COOH
(CH2)2NH2(CH2)2OH SO3H
B97D/6-31+G(d,p);LANL2DZ(Hg)
![Page 34: Computer Aided Design of Molecular Recognition Agents](https://reader030.vdocument.in/reader030/viewer/2022020218/5597631d1a28abe0778b47c5/html5/thumbnails/34.jpg)
Calix[6]-Hg2+
t-bu i-pr COOH
(CH2)2NH2 (CH2)2OH SO3H
B97D/6-31+G(d,p);LANL2DZ(Hg)
![Page 35: Computer Aided Design of Molecular Recognition Agents](https://reader030.vdocument.in/reader030/viewer/2022020218/5597631d1a28abe0778b47c5/html5/thumbnails/35.jpg)
175
200
225
250
275
300
325
350
4 5 6
Ein
t (k
cal/
mo
l)
n
CO2H
Isopropilo
NH2
OH
SO3H
Terbutilo
n R COOH i-pr NH2 OH SO3H t-bu
4 0.306 0.407 0.357 0.348 0.561 0.405
5 0.318 0.354 0.340 0.383 0.376 0.394
6 0.367 0.370 0.387 0.374 0.350 0.375
Eint B97D/6-31+G(d,p);LANL2DZ(Pb)
Pb2+
![Page 36: Computer Aided Design of Molecular Recognition Agents](https://reader030.vdocument.in/reader030/viewer/2022020218/5597631d1a28abe0778b47c5/html5/thumbnails/36.jpg)
Mapa de Densidad Electrónica
n = 5; R = COOH B97D/6-31+G(d,p);LANL2DZ(M2+)
Hg2+ Pb2+
Efecto del radio iónico y el poder polarizante de cada ion.
Eint = 242.8 kcal/mol Eint = 199.54 kcal/mol
![Page 37: Computer Aided Design of Molecular Recognition Agents](https://reader030.vdocument.in/reader030/viewer/2022020218/5597631d1a28abe0778b47c5/html5/thumbnails/37.jpg)
Extracción de arsénico
R = SO3H; PO3H; EtOHn = 4, 5, 6, 8
M06-2X/6-311+G(d,p) SCRF(PCM,H2O)
As0; As3+; As5+; As2O3; As2O5
As2O3)Eint n = 4, R = SO3H : 13.99 kcal/molEint n = 4, R = EtOH : 8.49 kcal/mol
![Page 38: Computer Aided Design of Molecular Recognition Agents](https://reader030.vdocument.in/reader030/viewer/2022020218/5597631d1a28abe0778b47c5/html5/thumbnails/38.jpg)
CATALISIS ORGANOMETÁLICA
![Page 39: Computer Aided Design of Molecular Recognition Agents](https://reader030.vdocument.in/reader030/viewer/2022020218/5597631d1a28abe0778b47c5/html5/thumbnails/39.jpg)
“The Weak Link Approach”
= M. Transición d8 (Pt, Rh, Pd)
= Ligante lábil (S, N, O)
= Efector alostérico
= Ligante fuerte (PPh2)
Gianneschi, Masar III, Mirkin, Acc. Chem. Res. (2005), 40, 2022Yoon, Kuwabara, Kim, Mirkin, Science (2010), 330, 66
![Page 40: Computer Aided Design of Molecular Recognition Agents](https://reader030.vdocument.in/reader030/viewer/2022020218/5597631d1a28abe0778b47c5/html5/thumbnails/40.jpg)
![Page 41: Computer Aided Design of Molecular Recognition Agents](https://reader030.vdocument.in/reader030/viewer/2022020218/5597631d1a28abe0778b47c5/html5/thumbnails/41.jpg)
Estructuras cristalinas (XRD)
![Page 42: Computer Aided Design of Molecular Recognition Agents](https://reader030.vdocument.in/reader030/viewer/2022020218/5597631d1a28abe0778b47c5/html5/thumbnails/42.jpg)
Méndez-Arroyo, J.; Barroso-Flores, J; Mirkin, C. JACS (2014) en preparación
Host Guest Complex
Semi-Open
conformation
Dipole moment
[D] 19.02 4.30 13.29
Open conformation
Dipole moment
[D] 3.34 1.08 6.20
La inserción procede por alineación antiparalela de los dipolos .(XRD – Isosuperficies = 0.002 eÅ-3; B97D/LANL2DZ)
![Page 43: Computer Aided Design of Molecular Recognition Agents](https://reader030.vdocument.in/reader030/viewer/2022020218/5597631d1a28abe0778b47c5/html5/thumbnails/43.jpg)
QUIMIOSENSORES FLUORESCENTES
![Page 44: Computer Aided Design of Molecular Recognition Agents](https://reader030.vdocument.in/reader030/viewer/2022020218/5597631d1a28abe0778b47c5/html5/thumbnails/44.jpg)
Disulfonatos de Hg(II) –Sensores inmobilizados–
• Dr. Alireza Badiei (U. Teherán, Irán) • Acido 1-amino-8-naftol-3,6-disulfónico soportado sobre sílica mesoporosa (SB15)
• Altamente selectivo a Hg(II)• Espectroscopía fluorescencia• TD-DFT: PBE0PBE/6-311++G(d,p)• M = Ag; Cd; Cu; Ni; Fe
Zarabadi-Poor, P., Badiei, A., Yousefi, A. A., & Barroso-Flores, J. (2013). J. Phys. Chem. C. 117(18), 9281-9289 DOI:10.1021/jp401479z
![Page 45: Computer Aided Design of Molecular Recognition Agents](https://reader030.vdocument.in/reader030/viewer/2022020218/5597631d1a28abe0778b47c5/html5/thumbnails/45.jpg)
ORDEN LOCAL DE ENLACE
![Page 46: Computer Aided Design of Molecular Recognition Agents](https://reader030.vdocument.in/reader030/viewer/2022020218/5597631d1a28abe0778b47c5/html5/thumbnails/46.jpg)
• Originalmente el OLE surgió del interés por describir interacciones secundarias en complejos anisobidentados con metales representativos pesados (Sn).
• Interacción secundaria: Distancia interatómica es menor a la suma de los radios de van der Waals (Allcock, 1972)
Un Orbital Molecular, Ψi
queda descrito por:
Proyectando sobre la base de los orbitales atómicos de dos átomos
Barroso-Flores, J., et al. (2004). J. OrganometallicChem. 689(12), 2096–2102.
![Page 47: Computer Aided Design of Molecular Recognition Agents](https://reader030.vdocument.in/reader030/viewer/2022020218/5597631d1a28abe0778b47c5/html5/thumbnails/47.jpg)
El dímero de HF como primer caso de estudio
12 lbo-dimer-m06-C.txt sto3g
H1 F2 H3 F4
H1 2.77E+00 0.00E+00 0.00E+00 0.00E+00
F2 -7.68E-01 1.09E+01 0.00E+00 0.00E+00
H3 -4.32E-03 -9.04E-02 2.89E+00 0.00E+00
F4 7.43E-05 1.51E-03 -7.91E-01 1.08E+01
22 lbo-dimer-m06-B.txt 3.21G(d,p)
H1 F2 H3 F4
H1 6.85E+00 0.00E+00 0.00E+00 0.00E+00
F2 -2.79E+00 2.16E+01 0.00E+00 0.00E+00
H3 -6.36E-02 -8.99E-01 8.36E+00 0.00E+00
F4 1.45E-03 4.88E-02 -3.40E+00 2.13E+01
38 lbo-dimer-m06-D.txt cc-pVDZ
H1 F2 H3 F4
H1 3.23E+01 0.00E+00 0.00E+00 0.00E+00
F2 -2.19E+01 5.13E+01 0.00E+00 0.00E+00
H3 -4.34E-01 -1.52E+00 3.20E+01 0.00E+00
F4 1.82E-02 1.03E-01 -2.00E+01 4.79E+01
40 lbo-dimer-m06.txt 6-31G(d,p)
H1 F2 H3 F4
H1 3.53E+01 0.00E+00 0.00E+00 0.00E+00
F2 -2.52E+01 5.79E+01 0.00E+00 0.00E+00
H3 -1.05E-01 -3.44E+00 4.62E+01 0.00E+00
F4 1.30E-03 7.66E-01 -3.26E+01 6.19E+01
48 lbo-dimer-m06-A.txt 6-311G(d,p)
H1 F2 H3 F4
H1 4.90E+01 0.00E+00 0.00E+00 0.00E+00
F2 -3.67E+01 7.52E+01 0.00E+00 0.00E+00
H3 -2.78E-01 -3.17E+00 5.09E+01 0.00E+00
F4 1.28E-02 6.50E-01 -3.54E+01 7.08E+01
64 lbo-dimer-m06-E.txt aug-cc-pVDZ
H1 F2 H3 F4
H1 1.03E+03 0.00E+00 0.00E+00 0.00E+00
F2 -9.54E+02 1.11E+03 0.00E+00 0.00E+00
H3 -3.48E+01 -2.94E+01 8.99E+02 0.00E+00
F4 -2.13E+01 -8.29E+01 -8.17E+02 9.67E+02
12 lbo-dimer-C-b3lyp.txt sto3g
H1 F2 H3 F4
H1 2.74E+00 0.00E+00 0.00E+00 0.00E+00
F2 -7.34E-01 1.08E+01 0.00E+00 0.00E+00
H3 -4.79E-03 -1.07E-01 2.87E+00 0.00E+00
F4 8.01E-05 1.82E-03 -7.55E-01 1.08E+01
22 lbo-dimer-B-b3lyp.txt 3-21g*
H1 F2 H3 F4
H1 6.81E+00 0.00E+00 0.00E+00 0.00E+00
F2 -2.75E+00 2.16E+01 0.00E+00 0.00E+00
H3 -6.38E-02 -9.15E-01 8.33E+00 0.00E+00
F4 1.44E-03 4.95E-02 -3.36E+00 2.13E+01
38 lbo-dimer-D-b3lyp.txt cc-pVDZ
H1 F2 H3 F4
H1 3.20E+01 0.00E+00 0.00E+00 0.00E+00
F2 -2.15E+01 5.10E+01 0.00E+00 0.00E+00
H3 -4.34E-01 -1.54E+00 3.16E+01 0.00E+00
F4 1.79E-02 1.02E-01 -1.96E+01 4.75E+01
40 lbo-dimer-b3lyp.txt 6-31G(d,p)
H1 F2 H3 F4
H1 3.49E+01 0.00E+00 0.00E+00 0.00E+00
F2 -2.48E+01 5.75E+01 0.00E+00 0.00E+00
H3 -1.02E-01 -3.43E+00 4.56E+01 0.00E+00
F4 1.21E-03 7.55E-01 -3.21E+01 6.13E+01
48 lbo-dimer-A-b3lyp.txt 6-311G(d,p)
H1 F2 H3 F4
H1 4.80E+01 0.00E+00 0.00E+00 0.00E+00
F2 -3.58E+01 7.42E+01 0.00E+00 0.00E+00
H3 -2.67E-01 -2.97E+00 4.98E+01 0.00E+00
F4 1.15E-02 5.96E-01 -3.46E+01 6.99E+01
64 lbo-dimer-E-b3lyp.txt aug-cc-pVDZ
H1 F2 H3 F4
H1 1.02E+03 0.00E+00 0.00E+00 0.00E+00
F2 -9.47E+02 1.09E+03 0.00E+00 0.00E+00
H3 -3.39E+01 -2.52E+01 8.79E+02 0.00E+00
F4 -1.96E+01 -7.47E+01 -8.02E+02 9.42E+02
• HF• MP2• CI• B3LYP• M062X
• STO3G (12)• 3-21G* (22)• cc-pVDZ (38)• 6-31G(d,p) (40)• 6-311G(d,p) (48)• aug-cc-pVDZ (64)
![Page 48: Computer Aided Design of Molecular Recognition Agents](https://reader030.vdocument.in/reader030/viewer/2022020218/5597631d1a28abe0778b47c5/html5/thumbnails/48.jpg)
-30
-25
-20
-15
-10
-5
0
10 20 30 40 50 60 70
LBO
Number of basis functions
LBO H(2)...F(3)
H-F
B3LYP
M06-2X
MP2
CI
![Page 49: Computer Aided Design of Molecular Recognition Agents](https://reader030.vdocument.in/reader030/viewer/2022020218/5597631d1a28abe0778b47c5/html5/thumbnails/49.jpg)
-30
-25
-20
-15
-10
-5
0
5
10 20 30 40 50 60 70
BO
ND
IND
EX (
WIB
ERG
& L
BO
)
Number of basis functions
LBO vs Wiberg BI - H(2)...F(3)
LBO HF
LBO B3LYP
LBO M06-2X
LBO MP2
LBO CI
WBG HF
WBG B3LYP
WBG M06-2X
WBG MP2
WBG CI
Queda mucho trabajo por hacer…
![Page 50: Computer Aided Design of Molecular Recognition Agents](https://reader030.vdocument.in/reader030/viewer/2022020218/5597631d1a28abe0778b47c5/html5/thumbnails/50.jpg)
Agradecimientos• Financiamiento e Infraestructura
• Instituto de Química
• DGAPA (IACOD; PAPIIT)• CONACyT (CB2012-01)• DGTIC (Kan Balam; NES)
• Colaboradores Prof. Dr. Chad Mirkin (Northwestern U.)
Dr. José Mendez Arroyo
Prof. Alireza Badiei (U. de Teherán, Irán) Dr. Pezhman Zarabadi-Poor
Dr. Eddie López-Honorato (CINVESTAV – Unidad Saltillo) Dr. Rodrigo Galindo Murillo (Utah U; AMBER)
• Estudiantes Q. María Eugenia Sandoval Salinas Howard Yoav Díaz Salazar Luís Enrique Aguilar Rodríguez Guillermo Caballero M. en C. Monserrat Enríquez
![Page 51: Computer Aided Design of Molecular Recognition Agents](https://reader030.vdocument.in/reader030/viewer/2022020218/5597631d1a28abe0778b47c5/html5/thumbnails/51.jpg)
Gracias por su atención