Profesor Titular
Laboratorio de Química Medicinal y Orgánica
Instituto de Química y Bioquímica
Facultad de Ciencias
Universidad de Valparaíso
Docencia
Pregrado:
- Química Orgánica I (BMR213)
- Química Orgánica Ambiental (IAM212)
- Química Orgánica I, Laboratorio (LCBQ212)
- Laboratorio Químico (QIM101A)
- Química Orgánica II, Laboratorio (LCBQ222)
- Estructura de la Materia (ICB421)
Postgrado:
- Química Medicinal (QPG3326)
- Química Orgánica Avanzada
Oferta de Tesis a alumnos de Pregrado y Postgrado
“Diseño racional y síntesis de nuevos derivados heterocíclicos de tipo benzoimidazol-etanolamina con potencial actividad ß3 adrenérgica”
“Construcción de un modelo farmacofórico mediante la técnica 3D-QSAR para el desarrollo de nuevos ligandos ß3-adrenérgicos”
- Área: Química medicinal/Síntesis orgánica/ Estudios CoMFA (3D-QSAR)
- Tipo de Tesis: Experimental / Computacional
- Lugar: 5° Piso, Facultad de Ciencias. Departamento de Química y Bioquímica. Universidad de Valparaíso. Av. Gran Bretaña 1111.
- Requisitos personales: Responsabilidad, iniciativa y gusto por el trabajo en laboratorio o computacional
- Tiempo de ejecución: 1, 5- 2 semestres.
- Interesados contactarse con el profesor Jaime Mella: jaime.mella@uv.cl
Líneas de Investigación
Nuestro grupo se dedica a la formulación de estudios cuantitativos de relación estructura actividad (QSAR), con el fin de obtener modelos validados para el diseño de nuevos compuestos bioactivos (fármacos) que sean prometedores para el tratamiento de patologías humanas de relevancia.
En los estudios QSAR se busca correlacionar las propiedades fisicoquímicas de una serie de compuestos con sus actividades biológicas, con el fin de crear ecuaciones útiles para el diseño de nuevas moléculas (Figura 1), o para explicar retrospectivamente el comportamiento de los compuestos y sus mecanismos
de acción.
Figura 1. Esquema que representa la formulación de un estudio QSAR.
Actualmente hemos desarrollado y publicado modelos para varias patologías, mostramos algunas en la tabla siguiente.
Dentro de los métodos empleados, hemos utilizado técnicas clásicas de Hansch, análisis de Free-Wilson, hemos creado modelos combinados, utilizando descriptores cuánticos y topológicos, además de la generación de modelos 3D-QSAR (CoMFA, CoMSIA) que permiten una visualización simple y directa de los resultados a través de mapas de contorno. En la siguiente figura se muestra el resultado de mapas de contorno estéricos y electrostáticos obtenidos para heterociclos benzimidazoles estudiados por su capacidad de unión a los receptores de cannabinoides (Figura 2).
Figura 2. Mapas 3D-QSAR. Los resultados obtenidos para ligandos cannabinoides con afinidad CB1 y CB2 nos han permitido conocer los requisitos estructurales necesarios para conseguir selectividad para uno u otro tipo de receptor.
Áreas de Investigación / Especialidad
- Química Orgánica: Síntesis de Heterociclos: Benzimidazoles, benzofuranos, benzotiofenos.
- Química Medicina: Estudios de Relación Estructura-Actividad Cuantitativos (QSAR).
- Análisis de Free-Wilson, Análisis de Hansch, 3D-QSAR: CoMFA y CoMSIA.
- Estudios de binding contra radioligandos en receptores acoplados a proteína G (GPCRs)
Proyectos de Investigación
- FONDECYT Regular N° 1191330 (2019-2023) Synthesis of new brassinosteroid analogs with structural changes in the side chain. Evaluation of growth promoting effect and in silico structure-activity studies. (Co-investigador)
Publicaciones
- D. Cabezas, G. Mellado, N. Espinoza, JA. Gárate, C. Morales, A. Castro-Alvarez,MJ. Matos,M. Mellado, J. Mella. In silico approaches to develop new phenyl-pyrimidines as glycogen synthase kinase 3 (GSK-3) inhibitors with halogen-bonding capabilities: 3D-QSAR CoMFA/CoMSIA, molecular docking and molecular dynamics studies. Journal of Biomolecular Structure and Dynamics, 2023, https://doi.org/10.1080/07391102.2023.2172457
- M. Lorca, M. Faúndez, C. D. Pessoa-Mahana, G. Recabarren-Gajardo, B. Diethelm-Varela, D. Millán, I. Celik, M. Mellado, I. Araque, J. Mella, J. Romero-Parra. Design of benzimidazoles, benzoxazoles, benzothiazoles and thiazolopyridines as leukotriene A4 hydrolase inhibitors through 3D-QSAR, docking and molecular dynamics. J. Serb. Chem. Soc. 88 (1) 25–39 (2023) https://doi.org/10.2298/JSC220427068L
- Marcos Lorca, David Cabezas, Ileana Araque, Andrés Terán, Santiago Hernández, Marco Mellado, Luis Espinoza, Jaime Mella. Cancer and Brassinosteroids: mechanisms of action, SAR and future perspectives. Steroids, 2023 (190) 109153. https://doi.org/10.1016/j.steroids.2022.10915
- M. Paulino, C. Espinosa-Bustos, J. Bertrand, D. Cabezas, J. Mella, B. Dávila, H. Cerecetto, A. Ballesteros-Casallas and C.O. Salas. Development of 3D-QSAR and pharmacophoric models to design new anti-Trypanosoma cruzi agents based on 2-aryloxynaphthoquinone scaffold. 2022. SAR and QSAR in Environmental Research. 2022, Vol 33, No. 9, 701–728. https://doi.org/10.1080/1062936X.2022.2120069
- Jeanluc Bertrand, Hana Dostálová, Vladimír Kryštof, Radek Jorda, Thalía Delgado, Alejandro Castro-Alvarez, Jaime Mella, David Cabezas, Mario Faúndez, Christian Espinosa-Bustos and Cristian O. Salas. Design, Synthesis, In Silico Studies and Inhibitory Activity towards Bcr-Abl, BTK and FLT3-ITD of New 2,6,9-Trisubstituted Purine Derivatives as Potential Agents for the Treatment of Leukaemia. Pharmaceutics 2022, 14, 1294. https://doi.org/10.3390/pharmaceutics14061294
- Ulviye Acar Çevik, Ismail Celik, Jaime Mella, Marco Mellado, Yusuf Özkay, and Zafer Asım Kaplancıklı. Design, Synthesis, and Molecular Modeling Studies of a Novel Benzimidazole as an Aromatase Inhibitor. ACS Omega 2022, 7, 18, 16152–16163. https://doi.org/10.1021/acsomega.2c01497
- Meryem Erol, Ismail Celik, Begüm Nurpelin Sağlık, Arzu Karayel, MarcoMellado, Jaime Mella. Synthesis, Molecular Modeling, 3D-QSAR and Biological Evaluation Studies of New Benzimidazole Derivatives as Potential MAO-A and MAO-B Inhibitors. Journal of Molecular Structure. Available online 3 June 2022, 133444. In Press, Journal Pre-proof. https://doi.org/10.1016/j.molstruc.2022.133444
- Marco Mellado, Mauricio Reyna-Jeldes, Caroline Weinstein-Oppenheimer, Alejandra A. Covarrubias, Luis F. Aguilar, Claudio Coddou, Jaime Mella, Mauricio A. Cuellar. QSAR-driven synthesis of antiproliferative chalcones against SH-SY5Y cancer cells: Design, biological evaluation, and redesign. Arch Pharm (Weinheim) 2022 Apr 18;e2200042. doi: 10.1002/ardp.202200042. Online ahead of print.
- Marco Mellado, César González, Jaime Mella, Luis F. Aguilar, Ismail Celik, Fernanda Borges, Eugenio Uriarte, Giovanna DeloguDolores Viña Maria J. Matos. Coumarin-Resveratrol-Inspired Hybrids as Monoamine Oxidase B Inhibitors: 3-Phenylcoumarin versus trans-6-Styrylcoumarin. Molecules 2022, 27(3), 928; https://doi.org/10.3390/molecules27030928
- Arrieta-Rodríguez, L.; Espinoza-Rosales, D.; Vera, G.; Cho, Y.H.; Cabezas, D.; Vásquez-Velásquez, D.; Mella-Raipán, J.; Lagos, C.F.; Recabarren-Gajardo, G. Novel N-Arylsulfonylindoles Targeted as Ligands of the 5-HT6 Receptor. Insights on the Influence of C-5 Substitution on Ligand Affinity. Pharmaceuticals 2021, 14, 528. https://doi.org/10.3390/ph14060528
- Marco Mellado, César González, Jaime Mella, Luis F.Aguilar, Dolores Viña, Eugenio Uriarte, Mauricio Cuellar, Maria J.Matos. Combined 3D-QSAR and docking analysis for the design and synthesis of chalcones as potent and selective monoamine oxidase B inhibitors. Bioorg Chem, 2021 (108), 104689. https://doi.org/10.1016/j.bioorg.2021.104689
- C. Cerda-Cavieres, G. Quiroz, P. Iturriaga-Vásquez, J. Rodríguez-Lavado, J. Alarcón-Espósito, C. Saitz, C.D. Pessoa-Mahana, H. Chung, R. Araya-Maturana, J. Mella-Raipán, D. Cabezas, C. Ojeda-Gómez, M. Reyes-Parada, H. Pessoa-Mahana. Synthesis, Docking, 3-D-Qsar, and Biological Assays of Novel Indole Derivatives Targeting Serotonin Transporter, Dopamine D2 Receptor, and Mao-A Enzyme: In the Pursuit for Potential Multitarget Directed Ligands, Molecules. 25 (2020) 4614. https://doi.org/10.3390/molecules25204614.
- Marco Mellado, Jaime Mella, César González, Dolores Viña, Eugenio Uriarte, Maria J. Matos. 3-Arylcoumarins as highly potent and selective monoamine oxidase B inhibitors: Which chemical features matter? Bioorg Chem 2020, 101, 103964 (https://doi.org/10.1016/j.bioorg.2020.103964)
Jaime Mella, Javier Romero-Parra, and Gonzalo Recabarren-Gajardo. DARK Classics in Chemical Neuroscience: Heroin and Desomorphine. ACS Chem Neurosci 2020, 11, 23, 3905–3927 (https://doi.org/10.1021/acschemneuro.0c00262) - Rodríguez-Lavado, J., Gallardo-Garrido, C., Mallea, M., Bustos, V., Osorio, R., Hödar-Salazar, M., Chung, H., raya-Maturana, R., Lorca, M., Pessoa-Mahana, C. D., Mella-Raipán, J., Saitz, C., Jaque, P., Reyes-Parada, M., Iturriaga-Vásquez, P., and Pessoa-Mahana, H. Synthesis, in vitro evaluation and molecular docking of a new class of indolylpropyl benzamidopiperazines as dual AChE and SERT ligands for Alzheimer’s disease. Eur J Med Chem 2020, 198, 112368.
- C, O. S.; Zarate, A. M.; Krystof, V.; Mella, J.; Faundez, M.; Brea, J.; Loza, M. I.; Brito, I.; Hendrychova, D.; Jorda, R.; Cabrera, A. R.; Tapia, R. A.; Espinosa-Bustos, C., Promising 2,6,9-Trisubstituted Purine Derivatives for Anticancer Compounds: Synthesis, 3D-QSAR, and Preliminary Biological Assays. Int J Mol Sci 2020, 21(1), 161.
- Bertrand, J.; Dostalova, H.; Krystof, V.; Jorda, R.; Castro, A.; Mella, J.; Espinosa-Bustos, C.; Maria Zarate, A.; Salas, C. O., New 2,6,9-trisubstituted purine derivatives as Bcr-Abl and Btk inhibitors and as promising agents against leukemia. Bioorg Chem 2020(94), 103361.(https://doi.org/10.1016/j.bioorg.2019.103361).
- C, O. S.; Zarate, A. M.; Krystof, V.; Mella, J.; Faundez, M.; Brea, J.; Loza, M. I.; Brito, I.; Hendrychova, D.; Jorda, R.; Cabrera, A. R.; Tapia, R. A.; Espinosa-Bustos, C., Promising 2,6,9-Trisubstituted Purine Derivatives for Anticancer Compounds: Synthesis, 3D-QSAR, and Preliminary Biological Assays. Int J Mol Sci 2019, 21.
- González-Gutiérrez, J.P.; Pessoa-Mahana, H.A.; Iturriaga-Vásquez, P.E.; Reyes-Parada, M.I.; Guerra-Díaz, N.E.; Hodar-Salazar, M.; Viscarra, F.; Paillali, P.; Núñez-Vivanco, G.; Lorca-Carvajal, M.A.; Mella-Raipán, J.; Zúñiga, M.C. Synthesis of Novel Nicotinic Ligands with Multimodal Action: Targeting Acetylcholine α4β2, Dopamine and Serotonin Transporters. Molecules 2019, 24, 3808 (https://doi.org/10.3390/
molecules24203808). - Mellado, M., Espinoza, L., Madrid, A., Mella, J., Chávez-Weisser, E., Díaz, K., Cuellar, M. Design, synthesis, antifungal activity, and structure–activity relationship studies of chalcones and hybrid dihydrochromane–chalcones. Mol Divers (2019). (https://doi.org/10.1007/s11030-019-09967-y).
- Suarez-Rozas, C.; Simpson, S.; Fuentes-Retamal, S.; Catalan, M.; Ferreira, J.; Theoduloz, C.; Mella, J.; Cabezas, D.; Cassels, B. K.; Yanez, C.; Castro-Castillo, V., Antiproliferative and proapoptotic activities of aza-annulated naphthoquinone analogs. Toxicol In Vitro 2019, 54, 375-390.
- Lorca, M.; Valdes, Y.; Chung, H.; Romero-Parra, J.; Pessoa-Mahana, C. D.; Mella, J., Three-Dimensional Quantitative Structure-Activity Relationships (3D-QSAR) on a Series of Piperazine-Carboxamides Fatty Acid Amide Hydrolase (FAAH) Inhibitors as a Useful Tool for the Design of New Cannabinoid Ligands. Int J Mol Sci 2019, 20(10), 2510.
- Espinosa-Bustos, C.; Mella, J.; Soto-Delgado, J.; Salas, C. O., State of the art of Smo antagonists for cancer therapy: advances in the target receptor and new ligand structures. Future Med Chem 2019, 11, (6), 615-636.
- Mellado, M.; Madrid, A.; Reyna, M.; Weinstein-Oppenheimer, C.; Mella, J.; Salas, C. O.; Sánchez, E.; Cuellar, M., Synthesis of chalcones with antiproliferative activity on the SH-SY5Y neuroblastoma cell line: Quantitative Structure–Activity Relationship Models. Med. Chem. Res. 2018, 27, (11), 2414–2425.
- Mellado, M.; Madrid, A.; Martínez, Ú.; Mella, J.; Salas, C. O.; Cuellar, M., Hansch’s analysis application to chalcone synthesis by Claisen–Schmidt reaction based in DFT methodology. Chem. Pap. 2018, 72, (3), 703-709.
- Lorca, M.; Morales-Verdejo, C.; Vasquez-Velasquez, D.; Andrades-Lagos, J.; Campanini-Salinas, J.; Soto-Delgado, J.; Recabarren-Gajardo, G.; Mella, J., Structure-Activity Relationships Based on 3D-QSAR CoMFA/CoMSIA and Design of Aryloxypropanol-Amine Agonists with Selectivity for the Human beta3-Adrenergic Receptor and Anti-Obesity and Anti-Diabetic Profiles. Molecules 2018, 23, (5).
- Lopez-Lira, C.; Alzate-Morales, J. H.; Paulino, M.; Mella-Raipan, J.; Salas, C. O.; Tapia, R. A.; Soto-Delgado, J., Combined molecular modelling and 3D-QSAR study for understanding the inhibition of NQO1 by heterocyclic quinone derivatives. Chem. Biol. Drug. Des. 2018, 91, (1), 29-38.
- Campanini-Salinas, J.; Andrades-Lagos, J.; Mella-Raipan, J.; Vasquez-Velasquez, D., Novel classes of antibacterial drugs in clinical development, a hope in post antibiotic era. Curr Top Med Chem 2018.
- Campanini-Salinas, J.; Andrades-Lagos, J.; Gonzalez Rocha, G.; Choquesillo-Lazarte, D.; Bollo Dragnic, S.; Faundez, M.; Alarcon, P.; Silva, F.; Vidal, R.; Salas-Huenuleo, E.; Kogan, M.; Mella, J.; Recabarren Gajardo, G.; Vasquez-Velasquez, D., A New Kind of Quinonic-Antibiotic Useful Against Multidrug-Resistant S. aureus and E. faecium Infections. Molecules 2018, 23, (7).
- Cañete-Molina, Á.; Espinosa-Bustos, C.; González-Castro, M.; Faúndez, M.; Mella, J.; Tapia, R. A.; Cabrera, A. R.; Brito, I.; Aguirre, A.; Salas, C. O., Design, synthesis, cytotoxicity and 3D-QSAR analysis of new 3,6-disubstituted-1,2,4,5-tetrazine derivatives as potential antitumor agents. Arabian J. Chem. 2017 (http://doi.org/10.1016/j.arabjc.2017.04.002).
- Romero-Parra, J.; Chung, H.; Tapia, R. A.; Faundez, M.; Morales-Verdejo, C.; Lorca, M.; Lagos, C. F.; Di Marzo, V.; David Pessoa-Mahana, C.; Mella, J., Combined CoMFA and CoMSIA 3D-QSAR study of benzimidazole and benzothiophene derivatives with selective affinity for the CB2 cannabinoid receptor. Eur. J. Pharm. Sci. 2017, 101, 1-10.
- Mella, J.; Villegas, F.; Morales-Verdejo, C.; Lagos, C. F.; Recabarren-Gajardo, G., Structure-Activity Relationships Studies on Weakly Basic N-Arylsulfonylindoles with an Antagonistic Profile in the 5-HT6 Receptor. J. Mol. Struct. 2017, 1139, 362-370.
- Ferrer-Pertuz, K.; Espinoza, L.; Mella, J., Insights into the Structural Requirements of Potent Brassinosteroids as Vegetable Growth Promoters Using Second-Internode Elongation as Biological Activity: CoMFA and CoMSIA Studies. Int J Mol Sci 2017, 18, (12).
- Apablaza, G.; Montoya, L.; Morales-Verdejo, C.; Mellado, M.; Cuellar, M.; Lagos, C. F.; Soto-Delgado, J.; Chung, H.; Pessoa-Mahana, C. D.; Mella, J., 2D-QSAR and 3D-QSAR/CoMSIA Studies on a Series of (R)-2-((2-(1H-Indol-2-yl)ethyl)amino)-1-Phenylethan-1-ol with Human beta(3)-Adrenergic Activity. Molecules 2017, 22, (3).
- Vera, G.; Lagos, C. F.; Almendras, S.; Hebel, D.; Flores, F.; Valle-Corvalan, G.; Pessoa-Mahana, C. D.; Mella-Raipan, J.; Montecinos, R.; Recabarren-Gajardo, G., Extended N-Arylsulfonylindoles as 5-HT(6) Receptor Antagonists: Design, Synthesis & Biological Evaluation. Molecules 2016, 21, (8).
- Romero-Parra, J.; Mella-Raipan, J.; Palmieri, V.; Allara, M.; Torres, M. J.; Pessoa-Mahana, H.; Iturriaga-Vasquez, P.; Escobar, R.; Faundez, M.; Di Marzo, V.; Pessoa-Mahana, C. D., Synthesis, binding assays, cytotoxic activity and docking studies of benzimidazole and benzothiophene derivatives with selective affinity for the CB2 cannabinoid receptor. Eur. J. Med. Chem. 2016, 124, 17-35.
- Espinosa-Bustos, C.; Lagos, C. F.; Romero-Parra, J.; Zarate, A. M.; Mella-Raipan, J.; Pessoa-Mahana, H.; Recabarren-Gajardo, G.; Iturriaga-Vasquez, P.; Tapia, R. A.; Pessoa-Mahana, C. D., Design, synthesis, biological evaluation and binding mode modeling of benzimidazole derivatives targeting the cannabinoid receptor type 1. Arch. Pharm. 2015, 348, (2), 81-8.
- Andrades, J.; Campanini, J.; Vasquez, D.; Silvestri, C.; Morales, C.; Romero, J.; Mella, J., A combined CoMFA and CoMSIA 3D-QSAR study of benzamide type antibacterial inhibitors of the FtsZ protein in drug-resistant Staphylococcus aureus. Sar. Qsar. Environ. Res. 2015, 26, (11), 925-42.
- Mella-Raipan, J.; Hernandez-Pino, S.; Morales-Verdejo, C.; Pessoa-Mahana, D., 3D-QSAR/CoMFA-based structure-affinity/selectivity relationships of aminoalkylindoles in the cannabinoid CB1 and CB2 receptors. Molecules 2014, 19, (3), 2842-61.
- Mella-Raipan, J. A.; Lagos, C. F.; Recabarren-Gajardo, G.; Espinosa-Bustos, C.; Romero-Parra, J.; Pessoa-Mahana, H.; Iturriaga-Vasquez, P.; Pessoa-Mahana, C. D., Design, synthesis, binding and docking-based 3D-QSAR studies of 2-pyridylbenzimidazoles–a new family of high affinity CB1 cannabinoid ligands. Molecules 2013, 18, (4), 3972-4001.
- Pessoa-Mahana, H.; Nunez, C. U.; Araya-Maturana, R.; Barria, C. S.; Zapata-Torres, G.; Pessoa-Mahana, C. D.; Iturriaga-Vasquez, P.; Mella-Raipan, J.; Reyes-Parada, M.; Celis-Barros, C., Synthesis, 5-hydroxytryptamine1A receptor affinity and docking studies of 3-[3-(4-aryl-1-piperazinyl)-propyl]-1H-indole derivatives. Chem. Pharm. Bull. 2012, 60, (5), 632-8.
- Recabarren-Gajardo, G.; Gacitúa, M.; Murueva, I.; Romero, J.; Espinosa-Bustos, C.; Mella-Raipán, J.; Valle, M. A. d.; Pessoa-Mahana, C. D.; Tapia, R., Synthesis, characterization, and electrochemical studies of new 5- and 6-nitro N-acyl-1H-indazoles. J. Phys. Org. Chem. 2011, 24, 1179-1187.
- López-Alarcón, C.; Lissi, E.; Hoffmann, P.; Mella, J.; Pessoa-Mahana, C. D.; Speisky, H.; Möller, M.; Ferrer-Sueta, G.; Denicola, A., Interaction of 5-aminosalicylic acid with nitrous acid: formation of the diazonium derivative and nitric oxide release. Can. J. Chem. 2011, 89, 628-638.
- Alvarez-Figueroa, M. J.; Pessoa-Mahana, C. D.; Palavecino-Gonzalez, M. E.; Mella-Raipan, J.; Espinosa-Bustos, C.; Lagos-Munoz, M. E., Evaluation of the membrane permeability (PAMPA and skin) of benzimidazoles with potential cannabinoid activity and their relation with the Biopharmaceutics Classification System (BCS). Aaps. Pharmsci. 2011, 12, (2), 573-8.
- Romero, M.; Rojano, B.; Mella-Raipan, J.; Pessoa-Mahana, C. D.; Lissi, E.; Lopez-Alarcon, C., Antioxidant capacity of pure compounds and complex mixtures evaluated by the ORAC-pyrogallol red assay in the presence of Triton X-100 micelles. Molecules 2010, 15, (9), 6152-67.
- Pessoa-Mahana, D.; Núñez, A.; Espinosa, C.; Mella-Raipán, J.; Pessoa-Mahana, H., Synthesis of a Novel Series of 4-Arylpiperazinyl Derivatives Linked to a 2-(Pyridin-3-yl)-1H-benzimidazole as New Delavirdine Analogues. J. Braz. Chem. Soc. 2010, 21, (1), 63-70.
- Pessoa-Mahana, D.; Espinosa-Bustos, C.; Mella-Raipán, J.; Canales-Pacheco, J.; Pessoa-Mahana, H., Microwave-assisted synthesis and regioisomeric structural elucidation of novel benzimidazo[1,2d][1,4]benzodiazepinone derivatives. ARKIVOC 2009, 12, 131-140.
- Vásquez, D.; Lagos, C. F.; Mella-Raipán, J.; González, L.; Ebensperger, R.; Alvarez-Figueroa, M. J.; Sáez, E.; Pessoa-Mahana, H.; Araya-Secchp, R.; González-Wong, A.; Pérez-Acle, T.; Pessoa-Mahana, C. D., 1-Benzoyl-2-(2-nitrophenyl)-1h-benzimidazole derivatives: A novel approach to the development of new hiv-1 reverse transcriptase inhibitors. J. Chil. Chem. Soc. 2007, 52, (4), 1281-1287.