X-ray structure and computational study for N-acryloyl-L-valine, a versatile monomer for preparing smart drug delivery carriers Gabriella Tamasi a , Mario Casolaro b , Renzo Cini a,⇑ a Dipartimento di Chimica, Università di Siena, I-53100 Siena, Italy b Dipartimento Farmaco-Chimico Tecnologico, Università di Siena, I-53100 Siena, Italy highlights " Structural characterization of monomeric N-acryloyl-L-valine. " Solvent effects (computed) do not alter much the XRD structure. " Analysis of weak interactions on monomer gives rational for loading host molecules on hydrogels. article info Article history: Received 26 January 2012 Received in revised form 19 June 2012 Accepted 25 June 2012 Available online 3 July 2012 Keywords: Acryloyl valine X-ray structure Density functional Semi-empirical quantum mechanics Hydrogels abstract The title compound (NAV) has been synthesized by the acylation reaction of L-valine with acryloyl chlo- ride, in alkaline solution. The X-ray crystal and molecular structure was solved and refined in the P212121 space group and was characterized by an almost coplanar H 2 C@CHAC(@O)AN(AH)AC system, C@CACAN, C@CAC@O and (C@)CAC(@O)AN(AH)AC torsion angles being +anti periplanar (+ap)(trans, +172(1)°), Àsyn periplanar (Àsp, cys)(À8(1)°), and (Àap, trans)(À175(1)°). The carboxylic group plane is almost perpendicular to the amide plane (dihedral angle: 83(1)°) and the O@CAC(AH)AN(AH) torsion angle isÀsp, cys (À28(1)°). The CAO bond distance at amide is 1.240(3) Å, whereas the CAO bond dis- tances at carboxylic group are 1.200(3) and 1.303(3) Å, respectively allowing an easy assignment of pro- tonation site. The molecule has been theoretically analyzed via the methods of density functional theory DFT and semi-empirical quantum mechanics at PM3 level (SEQMPM3) in order to examine the conformational surface at the gas phase and in the presence of solvent molecules. The DFT computations at B3LYP/ 6-311++G ** are the most reliable ones among those performed in this work (SEQMPM3, and B3LYP/ 6-31G ** ) as the agreement between computed and XRD bond parameters is excellent. Even the conforma- tions are very reliable and the effect of the solvent was evaluated in a box of water molecules (at SEQMPM3) and through the PCM method at DFT for water, methanol, chloroform and other solvents. Ó 2012 Elsevier B.V. All rights reserved. 1. Introduction Poly-electrolytes as soluble polymers or their derivatives in the form of hydrogels have important applications in the field of bio- logical materials; such materials can be used for the reconstruction of living tissues like deteriorated bones and cartilages [1], skin, li- ver [2] or growing factors for specific localized structures [3,4]. An- other field of applications for hydrogels is as carriers and deliverers of pharmaceutical compounds once the materials are loaded with a drug or a mixture of bioactive molecules. The ideal situation is reached when the loadable material is able to absorb high amounts of the drugs via non-covalent (labile) linkages [5–7]. In this latter case the loaded material can in principle be implanted in the living tissue possibly close to the solid pathology towards which it slowly and constantly releases the active species. Once the carrier is not significantly erodible and/or it is biodegradable and not toxic, this way seems to be excellent to circumvent undesired side effects to vital organs by the pharmaceutical compounds. In the case the syn- thetic hydrogel is in the form of dispersed micro- or nano-particles these latter can in principle be vehiculated through the blood and lymphatic system and in this way be able to reach specific malig- nant pathologies [8]. Amino-acid containing molecules have been widely used as monomers to synthesize poly-electrolytes and then hydrogels as carriers of drugs in the past recent years because they impart promising properties such as proper conformational flexi- bility, chemical inertness, and because of their predictable biocom- patibility. Recent relevant works are listed in [9–13]. As examples 0022-2860/$ - see front matter Ó 2012 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.molstruc.2012.06.051 ⇑ Corresponding author. Tel.: +39 0577 234368; fax: +39 0577 234254. E-mail address: renzo.cini@unisi.it (R. Cini). Journal of Molecular Structure 1029 (2012) 98–105 Contents lists available at SciVerse ScienceDirect Journal of Molecular Structure journal homepage: www.elsevier.com/locate/molstruc