Part 1: Experimental and theoretical studies of 2-cyano-2-isonitroso- N-piperidynylacetamide (HPiPCO), 2-cyano-2-isonitroso- N-morpholylacetamide (HMCO) and their Pt- and Pd-complexes Jessica Ratcliff a , Janina Kuduk-Jaworska b,⇑ , Henryk Chojnacki c , Victor Nemykin d , Nikolay Gerasimchuk a,⇑ a Department of Chemistry, Missouri State University, Temple Hall 431, Springfield, MO 65897, USA b Faculty of Chemistry, Wrocław University, F. Joliot-Curie 14, 50-383 Wroclaw, Poland c Institute of Physical and Theoretical Chemistry, Wroclaw University of Technology, Wyb. Wyspianskiego 27, 50-370 Wroclaw, Poland d Department of Chemistry and Biochemistry, University of Minnesota, Duluth, MN 55812, USA article info Article history: Received 11 September 2011 Received in revised form 15 November 2011 Accepted 3 December 2011 Available online 29 December 2011 Keywords: In vitro cytotoxicity Platinum(II) Palladium(II) Cyanoximes abstract The reaction between substituted cyan-acetamides NC–CH 2 –C(O)X (X = N-piperidyne or N-morpholyl residues) and gaseous methylnitrite CH 3 ONO in isopropanol at room temperature in the presence of a base within minutes leads to colorless cyanoximes 2-cyano-2-isonitroso-N-piperidynylacetamide (fur- ther as HPiPCO), and 2-cyano-2-isonitroso-N-morpholylacetamide (HMCO) in 70–90% yield. The depro- tonation of HPiPCO and HMCO with a base such as NaOEt affords anionic Na-salts, bright-yellow in color originated from n ? p / transitions in the nitroso-chromophore. Anionic cyanoximates react with aqueous solutions of K 2 MCl 4 (M = Pd, Pt) to form yellow-orange PdL 2 and dark blue-green polymeric [PtL 2 ] n (L = PiPCO  , MCO  ), which upon treatment with DMSO or DMF breaks down to pale-yellow mono- meric PtL 2 . Synthesized metal complexes were characterized by spectroscopic methods (IR, UV–Vis), measurement of the electric conductivity and the X-ray analysis. Both PdL 2 and PtL 2 exhibit non-electro- lyte behavior in DMSO and DMF. Crystal structures of Pd(PiPCO) 2 and Pt(PiPCO) 2 were determined and revealed the formation of the cis-complexes with nearly planar geometry around the metal core and an adoption of the cis-anti configuration by anions, in contrast to the trans–anti geometry in structures of uncomplexed HPiPCO and HMCO. Ab initio calculations were performed for all six compounds: two cyanoxime ligands and four Pd and Pt metal complexes. A very satisfactory agreement between the cal- culated and experimental values of geometrical parameters of all evaluated compounds was attained. The electron densities, energies of HOMO and LUMO orbitals and molecular electrostatic potentials were cal- culated as well. Ó 2011 Elsevier B.V. All rights reserved. 1. Introduction Although the history of successful application of platinum complexes in oncology (the chemotherapy) began three decades ago, the complexes of platinum(II) and platinum(IV) continue to serve as an abundant source of cytotoxic compounds. An early hit, cisplatin, and the follow-on drugs carboplatin and oxalilplatin, are still among the most frequently administered anticancer drugs of the cisplatin family. They account for the treatment of 40–80% of all cancer patients [1]. However, there has been limited progress in the discovery of new active members of the cisplatin drug family, particularly those with a broader or different spectrum of activity, an ability to overcome the intrinsic or acquired resistance of cancerous cells, and lesser side effects. In contrast, there are significant achievements in the development of active non-classical compounds, such as trans-platinum complexes [2], multinuclear complexes [3], and both Pt(II) and Pt(IV) complexes with non- traditional ligands including polypeptides [4]. In line with the idea of further exploration of new, non-traditional platinum complexes, a few years ago we found several cytotoxic bivalent Pd and Pt com- plexes with deprotonated MCO  and PiPCO  ligands that possess in vitro activity comparable to cisplatin [5]. These square-planar Pd and Pt complexes represent the first examples of a new group of active oxime-based bis-chelates. However, prior to current studies, no high-yield preparations of Pd,Pt-cyanoximates were developed, no direct structural information about these complexes was avail- able, and their electronic structure was not known as well. In the first part of this work we present: (a) developed experi- mental procedures for the synthesis of complexes; (b) data of the 0020-1693/$ - see front matter Ó 2011 Elsevier B.V. All rights reserved. doi:10.1016/j.ica.2011.12.005 ⇑ Corresponding authors. Tel.: +1 417 836 5165 (N. Gerasimchuk). E-mail addresses: janina.kuduk@gmail.com (J. Kuduk-Jaworska), NNGerasimchuk@ MissouriState.edu (N. Gerasimchuk). Inorganica Chimica Acta 385 (2012) 1–20 Contents lists available at SciVerse ScienceDirect Inorganica Chimica Acta journal homepage: www.elsevier.com/locate/ica