Z. Kristallogr. 2016; 231(11): 663–672 *Corresponding authors: James L. Wardell, Instituto de Tecnologia em Fármacos – Farmanguinhos, FioCruz –, Fundação Oswaldo Cruz, R. Sizenando Nabuco, 100, Manguinhos, 21041-250 Rio de Janeiro, RJ, Brazil; and Department of Chemistry, Aberdeen University of Aberdeen, AB 24 3UE, Scotland, E-mail: j.wardell@abdn.ac.uk; and Edward R.T. Tiekink, Research Centre for Chemical Crystallography, Faculty of Science and Technology, Sunway University, 47500 Bandar Sunway, Selangor Darul Ehsan, Malaysia, E-mail: edwardt@sunway.edu.my Walcimar T. Vellasco Junior: Instituto de Tecnologia em Fármacos – Farmanguinhos, FioCruz –, Fundação Oswaldo Cruz, R. Sizenando Nabuco, 100, Manguinhos, 21041-250 Rio de Janeiro, RJ, Brazil; and Departamento de Química Orgânica, Universidade Federal Fluminense, Instituto de Química, Outeiro de São João Batista, Centro, Niterói, 24020-141, Rio de Janeiro, Brazil Claudia R.B. Gomes: Instituto de Tecnologia em Fármacos – Farmanguinhos, FioCruz –, Fundação Oswaldo Cruz, R. Sizenando Nabuco, 100, Manguinhos, 21041-250 Rio de Janeiro, RJ, Brazil Thatyana R.A. Vasconcelos: Departamento de Química Orgânica, Universidade Federal Fluminense, Instituto de Química, Outeiro de São João Batista, Centro, Niterói, 24020-141, Rio de Janeiro, Brazil Alberto Otero-de-la-Roza: Department of Chemistry, University of British Columbia, Okanagan, 3247 University Way, Kelowna, British Columbia V1V 1V7, Canada Mukesh M. Jotani: Department of Physics, Bhavan’s Sheth R. A. College of Science, Ahmedabad, Gujarat 380001, India Walcimar T. Vellasco Junior, Claudia R.B. Gomes, Thatyana R.A. Vasconcelos, James L. Wardell*, Alberto Otero-de-la-Roza, Mukesh M. Jotani and Edward R.T. Tiekink* Crystallographic and computational study of t-butyl N-[3-hydroxy-1-phenyl-4-(pyridin- 2-ylsulfanyl)butan-2-yl]carbamate and its pyrimidin-2-yl analogue DOI 10.1515/zkri-2016-1990 Received July 17, 2016; accepted August 23, 2016; published online September 27, 2016 Abstract: The crystal structure analysis of the biologically- relevant title compound (1) shows the carbonyl-O2 and amide-H atoms to be anti, and perpendicular relationships between the carbamate residue and the pyridyl ring [dihe- dral angle = 84.60(10)°] and between the carbamate and aryl ring [74.84(11)°]; the rings are approximately co-planar [12.07(17)°]. An intramolecular hydroxyl-O–H···N(pyridyl) hydrogen bond that closes a S(7) loop is noted. Of interest is the observation that this hydrogen bond is not found in the structure of the pyrimidinyl analogue (2) which was characterised as a monohydrate, i.e. 2·H 2 O, in an earlier study. Density-functional theory calculations show the observed conformation in 1 is 2.0 kcal/mol more stable than the conformation where the intramolecular hydro- gen bond is absent. This energy difference reduces to ca 0.5 kcal/mol in the case of 2. The differences in molecu- lar conformations found for 1 and 2 are therefore ascribed to the dictates of overall molecular packing, in particular due to the influence of lattice water in 2·H 2 O. Keywords: conformation; crystal structure analysis; DFT; 2-Hydroxyethylamine cores; X-ray diffraction. Introduction Compounds having 2-hydroxyethylamine cores have useful biological activities as aspartyl protease enzymes inhibitors, [1, 2], as inhibitors of BACE-1 to combat Alzhei- mer’s disease [3], as anti-malarial agents [4–8], as anti- bacterial agents [7], and in the treatment of leishmaniasis/ HIV-1 co-infections [9]. In continuation of our structural studies on these and related compounds [10, 11], herein the crystal structure of the title compound, 1 (Figure 1) is described. During the analysis of the molecular structure of 1 it was apparent that an intramolecular hydroxyl- O–H···N(pyridyl) hydrogen bond had formed. This was unexpected as in the previously reported pyrimidin-2-yl analogue, 2, isolated as a monohydrate, no such hydrogen bond was formed [10]. While the absence of an intramo- lecular hydroxyl-O–H…N(pyrimidinyl) hydrogen bond in 2 might be related to the influence of a solvent molecule of water incorporated in the crystal lattice, the different behaviour was not anticipated as both compounds were prepared and recrystallised under very similar conditions [10]. Accordingly, it was thought of interest to complement the X-ray structural studies with quantum chemical calcu- lations in order to understand the different crystallisation outcomes/molecular conformations. The results of this investigation are reported herein.