Binding mechanism of the farnesoid X receptor marine antagonist suvanine reveals a strategy to forestall drug modulation on nuclear receptors. Design, synthesis, and biological evaluation of novel ligands

Journal of Medicinal Chemistry

Volumn 56, Issue 11, 2013, Pages 4701-4717

  Di Leva, Francesco Saverio ^a   Festa, Carmen ^b   D'Amore, Claudio ^c   De Marino, Simona ^b   Renga, Barbara ^c   D'Auria, Maria Valeria ^b   Novellino, Ettore ^b   Limongelli, Vittorio ^b   Zampella, Angela ^b   Fiorucci, Stefano ^c  

^a ISTITUTO ITALIANO DI TECNOLOGIA   (Italy)

^b UNIVERSITY OF NAPLES FEDERICO II   (Italy)

^c UNIVERSITY OF PERUGIA   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

BILE ACID; CELL NUCLEUS RECEPTOR; FARNESOID X RECEPTOR; LIGAND; NUCLEAR RECEPTOR COREPRESSOR; SESTERTERPENE; STEROID RECEPTOR COACTIVATOR 1; SUVANINE; UNCLASSIFIED DRUG;

ANIMAL CELL; ARTICLE; CONFORMATIONAL TRANSITION; DRUG DESIGN; DRUG SYNTHESIS; FETUS; LIGHT; MODULATION; MOLECULAR DOCKING; NONHUMAN; PROTEIN BINDING;

ANIMALS; BINDING SITES; CHENODEOXYCHOLIC ACID; CO-REPRESSOR PROTEINS; GENES, REPORTER; HEP G2 CELLS; HUMANS; LIGANDS; LUCIFERASES; MEMBRANE TRANSPORT PROTEINS; MOLECULAR DOCKING SIMULATION; MOLECULAR DYNAMICS SIMULATION; NUCLEAR RECEPTOR COACTIVATOR 1; PORIFERA; PROMOTER REGIONS, GENETIC; PROTEIN CONFORMATION; RECEPTORS, CYTOPLASMIC AND NUCLEAR; SESTERTERPENES; STRUCTURE-ACTIVITY RELATIONSHIP; TRANSCRIPTIONAL ACTIVATION;

EID: 84879060437     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm400419e     Document Type: Article

References (71)

1. Mangelsdorf, D. J.; Thummel, C.; Beato, M.; Herrlich, P.; Schütz, G.; Umesono, K.; Blumberg, B.; Kastner, P.; Mark, M.; Chambon, P.; Evans, R. M. The nuclear receptor superfamily: the second decade Cell 1995, 83, 835-839
2. Zubay, G. L.; Parson, W. W.; Vance, D. E. Principles of Biochemistry; Wm. C. Brown Communications, Inc., Dubuque, IA, 1995.
3. Giguere, V. Orphan nuclear receptors: from gene to function Endocr. Rev. 1999, 20, 689-724
4. Moras, D.; Gronemeyer, H. The nuclear receptor ligand-binding domain: structure and function Curr. Opin. Cell. Biol. 1998, 10, 384-391 (Pubitemid 28287050)
5. Glass, C. K.; Rosenfeld, M. G. The coregulator exchange in transcriptional functions of nuclear receptors Genes Dev. 2000, 14, 121-141 (Pubitemid 30070977)
6. Glass, C. K.; Rose, D. W.; Rosenfeld, M. G. Nuclear receptor coactivators Curr. Opin. Cell Biol. 1997, 9, 222-232 (Pubitemid 27135990)
7. Matias, P. M.; Donner, P.; Coelho, R.; Thomaz, M.; Peixoto, C.; Macedo, S.; Otto, N.; Joschko, S.; Scholz, P.; Wegg, A.; Bäsler, S.; Schäfer, M.; Egner, U.; Carrondo, M. A. Structural evidence for ligand specificity in the binding domain of the human androgen receptor. Implications for pathogenic gene mutations J. Biol. Chem. 2000, 275, 26164-26171
8. Mueller-Fahrnow, A.; Egner, U. Ligand-binding domain of estrogen receptors Curr. Opin. Biotechnol. 1999, 10, 550-556
9. Brzozowski, A. M.; Pike, A. C.; Dauter, Z.; Hubbard, R. E.; Bonn, T.; Engström, O.; Ohman, L.; Greene, G. L.; Gustafsson, J. A.; Carlquist, M. Molecular basis of agonism and antagonism in the oestrogen receptor Nature 1997, 389, 753-758 (Pubitemid 27458965)
10. Wurtz, J. M.; Bourguet, W.; Renaud, J. P.; Vivat, V.; Chambon, P.; Moras, D.; Gronemeyer, H. A canonical structure for the ligand-binding domain of nuclear receptors Nature Struct. Biol. 1996, 3, 87-94
11. Makishima, M.; Okamoto, A. Y.; Repa, J. J.; Tu, H.; Learned, R. M.; Luk, A.; Hull, M. V.; Lustig, K. D.; Mangelsdorf, D. J.; Shan, B. Identification of a nuclear receptor for bile acids Science 1999, 284, 1362-1365 (Pubitemid 29289663)
12. Parks, D. J.; Blanchard, S. G.; Bledsoe, R. K.; Chandra, G.; Consler, T. G.; Kliewer, S. A.; Stimmel, J. B.; Willson, T. M.; Zavacki, A. M.; Moore, D. D.; Lehmann, J. M. Bile acids: natural ligands for an orphan nuclear receptor Science 1999, 284, 1365-1368 (Pubitemid 29289664)
13. Moore, D. D.; Kato, S.; Xie, W.; Mangelsdorf, D. J.; Schmidt, D. R.; Xiao, R.; Kliewer, S. A. The NR1H and NR1I receptors: constitutive androstane receptor, pregnane X receptor, farnesoid X receptor α, farnesoid X receptor β, liver X receptor α, liver X receptor β, and vitamin D receptor Pharmacol. Rev. 2006, 58, 742-759 (Pubitemid 44833743)
14. Jonker, J. W.; Liddle, C.; Downes, M. FXR and PXR: potential therapeutic targets in cholestasis J. Steroid Biochem. Mol. Biol. 2012, 130, 147-158
15. Rizzo, G.; Renga, B.; Antonelli, E.; Passeri, D.; Pellicciari, R.; Fiorucci, S. The methyl transferase PRMT1 functions as co-activator of farnesoid X receptor (FXR)/9- cis retinoid X receptor and regulates transcription of FXR responsive genes Mol. Pharmacol. 2005, 68, 551-558 (Pubitemid 41058318)
16. Fiorucci, S.; Rizzo, G.; Donini, A.; Distrutti, E.; Santucci, L. Targeting FXR for liver and metabolic disorders Trends Mol. Med. 2007, 13, 298-309 (Pubitemid 47017005)
17. Fiorucci, S.; Mencarelli, A.; Distrutti, E.; Palladino, G.; Cipriani, S. Targeting farnesoid-X-receptor: from medicinal chemistry to disease treatment Curr. Med. Chem. 2010, 17, 139-159
18. Renga, B.; Migliorati, M.; Mencarelli, A.; Cipriani, S.; D'Amore, C.; Distrutti, E.; Fiorucci, S. Farnesoid X receptor suppresses constitutive androstane receptor activity at the multidrug resistance protein-4 promoter Biochim. Biophys. Acta 2011, 1809, 157-165
19. D'Auria, M. V.; Sepe, V.; Zampella, A. Natural ligands for nuclear receptors: biology and potential therapeutic applications Curr. Top. Med. Chem. 2012, 12, 637-669
20. Urizar, N. L.; Liverman, A. B.; Dodds, D. T.; Silva, F. V.; Ordentlich, P.; Yan, Y.; Gonzalez, F. J.; Heyman, R. A.; Mangelsdorf, D. J.; Moore, D. D. A natural product that lowers cholesterol as an antagonist ligand for FXR Science 2002, 296, 1703-1706 (Pubitemid 34579172)
21. Wu, J.; Xia, C.; Meier, J.; Li, S.; Hu, X.; Lala, D. S. The hypolipidemic natural product guggulsterone acts as an antagonist of the bile acid receptor Mol. Endocrinol. 2002, 16, 1590-1597 (Pubitemid 34743677)
22. Nozawa, H. Xanthohumol, the chalcone from beer hops (Humulus lupulus L.), is the ligand for farnesoid X receptor and ameliorates lipid and glucose metabolism in KK-Ay mice Biochem. Biophys. Res. Commun. 2005, 336, 754-761 (Pubitemid 41338333)
23. Burris, T. P.; Montrose, C.; Houck, K. A.; Osborne, H. E.; Bocchinfuso, W. P.; Yaden, B. C.; Cheng, C. C.; Zink, R. W.; Barr, R. J.; Hepler, C. D.; Krishnan, V.; Bullock, H. A.; Burris, L. L.; Galvin, R. J.; Bramlett, K.; Stayrook, K. R. The hypolipidemic natural product guggulsterone is a promiscuous steroid receptor ligand Mol. Pharmacol. 2005, 67, 948-954 (Pubitemid 40365342)
24. Fiorucci, S.; Distrutti, E.; Bifulco, G.; D'Auria, M. V.; Zampella, A. Marine sponge steroids as nuclear receptor ligands Trends Pharmacol. Sci. 2012, 33, 591-601
25. Carlson, E. E. Natural products as chemical probes ACS Chem. Biol. 2010, 5, 639-653
26. Sepe, V.; Bifulco, G.; Renga, B.; D'Amore, C.; Fiorucci, S.; Zampella, A. Discovery of sulfated sterols from marine invertebrates as a new class of marine natural antagonists of farnesoid-X-receptor J. Med. Chem. 2011, 54, 1314-1320
27. Festa, C.; De Marino, S.; D'Auria, M. V.; Bifulco, G.; Renga, B.; Fiorucci, S.; Petek, S.; Zampella, A. Solomonsterols A and B from Theonella swinhoei. The first example of C-24 and C-23 sulfated sterols from a marine source endowed with a PXR agonistic activity J. Med. Chem. 2011, 54, 401-405
28. De Marino, S.; Ummarino, R.; D'Auria, M. V.; Chini, M. G.; Bifulco, G.; Renga, B.; D'Amore, C.; Fiorucci, S.; Debitus, C.; Zampella, A. Theonellasterols and conicasterols from Theonella swinhoei. Novel marine natural ligands for human nuclear receptors J. Med. Chem. 2011, 54, 3065-3075
29. De Marino, S.; Sepe, V.; D'Auria, M. V.; Bifulco, G.; Renga, B.; Petek, S.; Fiorucci, S.; Zampella, A. Towards new ligands of nuclear receptors. Discovery of malaitasterol A, an unique bis-secosterol from marine sponge Theonella swinhoei Org. Biomol. Chem. 2011, 9, 4856-4862
30. Renga, B.; Mencarelli, A.; D'Amore, C.; Cipriani, S.; D'Auria, M. V.; Sepe, V.; Chini, M. G.; Monti, M. C.; Bifulco, G.; Zampella, A.; Fiorucci, S. Discovery that theonellasterol a marine sponge sterol is a highly selective FXR antagonist that protects against liver injury in cholestasis PLoS One 2012, 7, e30443
31. Manes, L. V.; Naylor, S.; Crews, P.; Bakus, G. J. Suvanine, a novel sesterterpene from an Ircinia marine sponge J. Org. Chem. 1985, 50, 284-286
32. Manes, L. V.; Crews, P.; Kernan, M. R.; Faulkner, D. J.; Fronczek, F. R.; Gandour, R. D. Chemistry and revised structure of suvanine J. Org. Chem. 1988, 53, 570-575
33. Pellicciari, R.; Fiorucci, S.; Camaioni, E.; Clerici, C.; Costantino, G.; Maloney, P. R.; Morelli, A.; Parks, D. J.; Willson, T. M. 6α-Ethyl- chenodeoxycholic acid (6-ECDCA), a potent and selective FXR agonist endowed with anticholestatic activity J. Med. Chem. 2002, 45, 3569-3572 (Pubitemid 34856095)
34. De Marino, S.; Festa, C.; D'Auria, M. V.; Bourguet-Kondracki, M.-L.; Petek, S.; Debitus, C.; Andrés, R. M.; Terencio, M. C.; Payá, M.; Zampella, A. Coscinolactams A and B: new nitrogen-containing sesterterpenoids from the marine sponge Coscinoderma mathewsi exerting anti-inflammatory properties Tetrahedron 2009, 65, 2905-2909
35. Downes, M.; Verdecia, M. A.; Roecker, A. J.; Hughes, R.; Hogenesch, J. B.; Kast-Woelbern, H. R.; Bowman, M. E.; Ferrer, J. L.; Anisfeld, A. M.; Edwards, P. A.; Rosenfeld, J. M.; Alvarez, J. G.; Noel, J. P.; Nicolaou, K. C.; Evans, R. M. A chemical, genetic, and structural analysis of the nuclear bile acid receptor FXR Mol. Cell 2003, 11, 1079-1092 (Pubitemid 36566328)
36. Mi, L. Z.; Devarakonda, S.; Harp, J. M.; Han, Q.; Pellicciari, R.; Willson, T. M.; Khorasanizadeh, S.; Rastinejad, F. Structural basis for bile acid binding and activation of the nuclear receptor FXR Mol. Cell 2003, 11, 1093-1100 (Pubitemid 36566329)
37. Soisson, S. M.; Parthasarathy, G.; Adams, A. D.; Sahoo, S.; Sitlani, A.; Sparrow, C.; Cui, J.; Becker, J. W. Identification of a potent synthetic FXR agonist with an unexpected mode of binding and activation Proc. Natl. Acad. Sci. U..S. A. 2008, 105, 5337-5342 (Pubitemid 351753864)
38. Akwabi-Ameyaw, A.; Bass, J. Y.; Caldwell, R. D.; Caravella, J. A.; Chen, L.; Creech, K. L.; Deaton, D. N.; Jones, S. A.; Kaldor, I.; Liu, Y.; Madauss, K. P.; Marr, H. B.; McFadyen, R. B.; Miller, A. B.; Navas, F., III; Parks, D. J.; Spearing, P. K.; Todd, D.; Williams, S. P.; Wisely, G. B. Conformationally constrained farnesoid X receptor (FXR) agonists: naphthoic acid-based analogs of GW 4064 Bioorg. Med. Chem. Lett. 2008, 18, 4339-4343
39. Bass, J. Y.; Caldwell, R. D.; Caravella, J. A.; Chen, L.; Creech, K. L.; Deaton, D. N.; Madauss, K. P.; Marr, H. B.; McFadyen, R. B.; Miller, A. B.; Parks, D. J.; Todd, D.; Williams, S. P.; Wisely, G. B. Substituted isoxazole analogs of farnesoid X receptor (FXR) agonist GW4064 Bioorg. Med. Chem. Lett. 2008, 19, 2969-2973
40. Akwabi-Ameyaw, A.; Bass, J. Y.; Caldwell, R. D.; Caravella, J. A.; Chen, L.; Creech, K. L.; Deaton, D. N.; Madauss, K. P.; Marr, H. B.; McFadyen, R. B.; Miller, A. B.; Navas, F., III; Parks, D. J.; Spearing, P. K.; Todd, D.; Williams, S. P.; Wisely, G. B. FXR agonist activity of conformationally constrained analogs of GW 4064 Bioorg. Med. Chem. Lett. 2009, 19, 4733-4739
41. Flatt, B.; Martin, R.; Wang, T.-L.; Mahaney, P.; Murphy, B.; Gu, X.-H.; Foster, P.; Li, J.; Pircher, P.; Petrowski, M.; Schulman, I.; Westin, S.; Wrobel, J.; Yan, G.; Bischoff, E.; Daige, C.; Mohan, R. Discovery of XL335 (WAY-362450), a highly potent, selective, and orally active agonist of the farnesoid X receptor (FXR) J. Med. Chem. 2009, 52, 904-907
42. Lundquist, J. T., IV; Harnish, D. C.; Kim, C. Y.; Mehlmann, J. F.; Unwalla, R. J.; Phipps, K. M.; Crawley, M. L.; Commons, T.; Green, D. M.; Xu, W.; Hum, W.-T.; Eta, J. E.; Feingold, I.; Patel, V.; Evans, M. J.; Lai, K.; Borges-Marcucci, L.; Mahaney, P. E.; Wrobel, J. E. Improvement of physiochemical properties of the tetrahydroazepinoindole series of farnesoid X receptor (FXR) agonists: beneficial modulation of lipids in primates J. Med. Chem. 2010, 53, 1774-1787
43. Richter, H. G. F.; Benson, G. M.; Blum, D.; Chaput, E.; Feng, S.; Gardes, C.; Grether, U.; Hartman, P.; Kuhn, B.; Martin, R. E.; Plancher, J.-M.; Rudolph, M. G.; Schuler, F.; Taylor, S.; Bleicher, K. H. Discovery of novel and orally active FXR agonists for the potential treatment of dyslipidemia and diabetes Bioorg. Med. Chem. Lett. 2011, 21, 191-194
44. Bass, J. Y.; Caravella, J. A.; Chen, L.; Creech, K. L.; Deaton, D. N.; Madauss, K. P.; Marr, H. B.; McFadyen, R. B.; Miller, A. B.; Mills, W. Y.; Navas, F., III; Parks, D. J.; Smalley, T. L., Jr.; Spearing, P. K.; Todd, D.; Williams, S. P.; Wisely, G. B. Conformationally constrained farnesoid X receptor (FXR) agonists: heteroaryl replacements of the naphthalene Bioorg. Med. Chem. Lett. 2011, 21, 1206-1213
45. Akwabi-Ameyaw, A.; Caravella, J. A.; Chen, L.; Creech, K. L.; Deaton, D. N.; Madauss, K. P.; Marr, H. B.; Miller, A. B.; Navas, F., III; Parks, D. J.; Spearing, P. K.; Todd, D.; Williams, S. P.; Wisely, G. B. Conformationally constrained farnesoid X receptor (FXR) agonists: alternative replacements of the stilbene Bioorg. Med. Chem. Lett. 2011, 21, 6154-6160
46. Huey, R.; Morris, G. M.; Olson, A. J.; Goodsell, D. S. A semiempirical free energy force field with charge-based desolvation J. Comput. Chem. 2007, 28, 1145-1152 (Pubitemid 46506716)
47. Limongelli, V.; Marinelli, L.; Cosconati, S.; La Motta, C.; Sartini, S.; Mugnaini, L.; Da Settimo, F.; Novellino, E.; Parrinello, M. Sampling protein motion and solvent effect during ligand binding Proc. Natl. Acad. Sci. U. S. A. 2012, 109, 1467-1472
48. Costantino, G.; Entrena-Guadix, A.; Macchiarulo, A.; Gioiello, A.; Pellicciari, R. Molecular dynamics simulation of the ligand binding domain of farnesoid X receptor. Insights into helix-12 stability and coactivator peptide stabilization in response to agonist binding J. Med. Chem. 2005, 48, 3251-3259 (Pubitemid 40628045)
49. Nolte, R. T.; Wisely, G. B.; Westin, S.; Cobb, J. E.; Lambert, M. H.; Kurokawa, R.; Rosenfeld, M. G.; Willson, T. M.; Glass, C. K.; Milburn, M. V. Ligand binding and co-activator assembly of the peroxisome proliferator- activated receptor-γ Nature 1998, 395, 137-143 (Pubitemid 28425645)
50. Perissi, V.; Staszewski, L. M.; McInerney, E. M.; Kurokawa, R.; Krones, A.; Rose, D. W.; Lambert, M. H.; Milburn, M. V.; Glass, C. K.; Rosenfeld, M. G. Molecular determinants of nuclear receptor-corepressor interaction Genes Dev. 1999, 13, 3198-3208 (Pubitemid 30030442)
51. Xu, H. E.; Lambert, M. H.; Montana, V. G.; Plunket, K. D.; Moore, L. B.; Collins, J. L.; Oplinger, J. A.; Kliewer, S. A.; Gampe, R. T., Jr.; McKee, D. D.; Moore, J. T.; Willson, T. M. Structural determinants of ligand binding selectivity between the peroxisome proliferator activated receptors Proc. Natl. Acad. Sci. U. S. A. 2001, 98, 13919-13924 (Pubitemid 33115999)
52. Feng, W.; Ribeiro, R. C.; Wagner, R. L.; Nguyen, H.; Apriletti, J. W.; Fletterick, R. J.; Baxter, J. D.; Kushner, P. J.; West, B. L. Hormone-dependent coactivator binding to a hydrophobic cleft on nuclear receptors Science 1998, 280, 1747-1749 (Pubitemid 28283497)
53. Henttu, P. M.; Kalkhoven, E.; Parker, M. G. AF-2 activity and recruitment of steroid receptor coactivator 1 to the estrogen receptor depend on a lysine residue conserved in nuclear receptors Mol. Cell. Biol. 1997, 17, 1832-1839 (Pubitemid 27133268)
54. Shiau, A. K.; Barstad, D.; Loria, P. M.; Cheng, L.; Kushner, P. J.; Agard, D. A.; Greene, G. L. The structural basis of estrogen receptor/coactivator recognition and the antagonism of this interaction by tamoxifen Cell 1998, 95, 927-937 (Pubitemid 29019045)
55. Kalgutkar, A. S.; Gardner, I.; Obach, R. S.; Shaffer, C. L.; Callegari, E.; Henne, K. R.; Mutlib, A. E.; Dalvie, D. K.; Lee, J. S.; Nakai, Y.; O'Donnell, J. P.; Boer, J.; Harriman, S. P. A comprehensive listing of bioactivation pathways of organic functional groups Curr. Drug. Metab. 2005, 161-225 (Pubitemid 40753853)
56. Kimura, J.; Hyosu, M. Two new sesterterpenes from the marine sponge Coscinoderma mathewsi Chem. Lett. 1999, 61-62
57. Bae, J.; Jeon, J. E.; Lee, Y. J.; Lee, H. S.; Sim, C. J.; Oh, K. B.; Shin, J. Sesterterpenes from the tropical sponge Coscinoderma sp J. Nat. Prod. 2011, 74, 1805-1811
58. Prime, version 3.1; Schrödinger, LLC: New York, 2012.
59. Wagner, B. L.; Pollio, G.; Giangrande, P.; Webster, J. C.; Breslin, M.; Mais, D. E.; Cook, C. E.; Vedeckis, W. V.; Cidlowski, J. A.; McDonnell, D. P. The novel progesterone receptor antagonists RTI 3021-012 and RTI 3021-022 exhibit complex glucocorticoid receptor antagonist activities: implications for the development of dissociated antiprogestins Endocrinology 1999, 140, 1449-1458 (Pubitemid 29104252)
60. Link, J. T.; Sorensen, B.; Patel, J.; Grynfarb, M.; Goos-Nilsson, A.; Wang, J.; Fung, S.; Wilcox, D.; Zinker, B.; Nguyen, P.; Hickman, B.; Schmidt, J. M.; Swanson, S.; Tian, Z.; Reisch, T. J.; Rotert, G.; Du, J.; Lane, B.; von Geldern, T. W.; Jacobson, P. B. Antidiabetic activity of passive nonsteroidal glucocorticoid receptor modulators J. Med. Chem. 2005, 48, 5295-5304 (Pubitemid 41113915)
61. Schoch, G. A.; D'Arcy, B.; Stihle, M.; Burger, D.; Bär, D.; Benz, J.; Thoma, R.; Ruf, A. Molecular switch in the glucocorticoid receptor: active and passive antagonist conformations J. Mol. Biol. 2010, 395, 568-577
62. Maestro, version 9.3; Schrödinger, LLC: New York, 2012.
63. Jorgensen, W. L.; Maxwell, D. S.; Tirado-Rives, J. Development and testing of the OPLS all-atom force field on conformational energetics and properties of organic liquids J. Am. Chem. Soc. 1996, 118, 11225-11236 (Pubitemid 26399746)
64. MacroModel, version 9.9; Schrödinger, LLC: New York, 2012.
65. Ligprep, version 2.5; Schrödinger, LLC: New York, 2012.
66. Epik, version 2.3; Schrödinger, LLC: New York, 2012.
67. Lindorff-Larsen, K.; Piana, S.; Palmo, K.; Maragakis, P.; Klepeis, J. L.; Dror, R. O.; Shaw, D. E. Improved side-chain torsion potentials for the Amber ff99SB protein force field Proteins 2010, 78, 1950-1958
68. Jorgensen, W. L.; Chandrasekhar, J.; Madura, J. D.; Impey, R. W.; Klein, M. L. Comparison of simple potential functions for simulating liquid water J. Chem. Phys. 1983, 79, 926-935
69. Bayly, C. I.; Cieplak, P.; Cornell, W. D.; Kollman, P. A. A well-behaved electrostatic potential based method using charge restraints for determining atom-centered charges: The RESP Model J. Phys. Chem. 1993, 97, 10269-10280
70. Gaussian09; Gaussian, Inc.: Wallingford, CT, 2009.
71. Wang, J.; Wang, W.; Kollman, P. A.; Case, D. A. Automatic atom type and bond type perception in molecular mechanics J. Mol. Graphics Modell. 2006, 25, 247-260 Compounds: From Discovery to Sustainable Production and Industrial Applications