Polyoxometalates for (Bio-)conjugation.

Ken Princen a , Anna M. Kaczmareka, Rik Van Deuna, Annemieke Madderb, Kristof Van Heckea

aDepartment of Inorganic and Physical Chemistry, Ghent University,Krijgslaan 281-S3, B-9000, Ghent, Belgium

bDepartment of Organic and Macromolecular Chemistry, Ghent University, Krijgslaan 281-S4, B-9000 Ghent, Belgium

ken.princen@ugent.be

Polyoxometalates (POMs) conserve an enormous class of polynuclear oxo-bridged early transition metal compounds with a rich topology and versatile chemical and physical properties.1 The comprehension of the relationships between the different cluster types can be bewildering. A general classification divides POMs into isopolyanions ([HxMyOz]n−) and heteropolyanions ([XxMmOy]q−, X = heteroatoms, more specifically the additionally complexed cations, e.g., a first-row transition metal). The isopolyanions are less stable than the heteropolyanions.2

In 2000, Lorenzo-Louis et al. published a cornerstone review about Anderson clusters (Fig. 1),3 from that moment on extensive field work has been done on this POM archetype. New research areas in biology are highlighted since it is becoming one of the go-to POMs for biological applications based on recent results in nanomaterials, macromolecular crystallography, tumor inhibiting and antiviral studies. In regard to the ability to connect particular organic ligands to inorganic POMs allows to produce POMs with specific organic functionalities and thus the generation of hybrid compounds is key to expanding those topics.4 -7

The Anderson polyoxoanion (Fig. 1, (a)) comprises of six edge-sharing MO6 (MoO6 or WO6) octahedra enclosing a central, edge-sharing heteroatom of octahedral geometry XO6 leading to a planar arrangement (Fig. 1, (b)). Anderson POMs (now abbreviated as POMs) have a vast number of physical, chemical and biological properties that all are greatly influenced by the heteroatom, counter cations and organic functionalization. Decoration of POMs with organic moieties opens new pathways for

Fig. 1 Ball-and-stick (a) and polyhedral representation (b) of the Anderson POM [XM6O24]n− shown as a top view and a side view consisting of the heteroatom (grey sphere, grey octahedron, X = e.g., a first-row transition metal), the addenda atoms (green spheres, green octahedra, M = WVI or MoVI) and the different types of oxygen atoms (red spheres) that make up the structure; triple bridged (μ3)

the synthesis of tailor-made POMs. POMs of the B-type, unlike the A-type, have six protons attached to μ3-O atoms (Fig. 1, (a)) which can be interchanged by diverse tris-ligands (RC(CH2OH)3, R = e.g., -NH2, -OH, -CH2OH), and subsequent manipulations with imine and amide bonds either before or after attachment to the POM). When these manipulations are done before grafting it onto the POM, this is termed as pre-functionalization. On the other hand, simple tris-ligands can be further complexed after POM attachment by organic reactions, called post-functionalization.

In our research endeavors were made by synthesizing the following POMs: (K5.5H1.5)[SbW6O24].6H2O, (Na3)[CrMo6O24H6].8H2O, [(n-C4H9)4N]4[Mo8O26], tris(hydroxymethyl)aminomethane-functionalized (Fig. 2 (a) single and (b) double sided) POMs (C16H36N)3{Cr(OH)3Mo6O18[(OCH2)3CNH2]}·12H2O and [N(C4H9)4]3[MnMo6O18{(OCH2)3CCH2OH}2], chloride-functionalized POM (Fig. 2, (c)) (C16H36N)3[MnMo6O18((OCH2)3C3H3NOCl)2] and azide-functionalized POM (Fig. 2, (d)) (C16H36N)3-[MnMo6O18((OCH2)3C3H3N4O)2]. The resulting compounds were structurally characterized by single crystal X-ray diffraction, elucidating new crystal structures. Envisaging a conjugation reaction with a suitable and functional compound (e.g. organic chromophore, cell-penetrating peptide, etc.).

1. M. T. Pope, A. Muller, Angew. Chem., Int. Ed. Engl, 30, 34 (1991).2. A. Blazevic, A. Rompel, Coordination Chemistry Reviews, 307, 42 (2016).3. P. A. Lorenzo-Luis, P. Gili, Recent Res Dev Inorg Chem, 2, 185 (2000).4. P. Gouzerh, A. Proust, Chemical Reviews 98, 77 (1998).5. C. Yvon, A. J. Surman, M. Hutin, J. Alex, B. O. Smith, D.-L. Long, L. Cronin,

Angewandte Chemie International Edition 53, 3336 (2014).6. S. Vanhaecht, J. Jacobs, L. Van Meervelt, T. N. Parac-Vogt, Dalton Trans. 44, 19059

(2015).7. G. Geisberger, E. B. Gyenge, D. Hinger, P. Bosiger, C. Maake, G. R. Patzke, Dalton

Trans. 42, 9914 (2013).

Fig. 2 Functionalized POMs: (a) single sided tris(hydroxymethyl)aminomethane (C16H36N)3{Cr(OH)3Mo6O18[(OCH2)3CNH2]}·12H2O, (b) double sided tris(hydroxymethyl)aminomethane [N(C4H9)4]3[MnMo6O18{(OCH2)3CCH2OH}2], (c) chloride-functionalized POM (C16H36N)3[MnMo6O18((OCH2)3C3H3NOCl)2], (d) azide-functionalized POM (C16H36N)3-[MnMo6O18((OCH2)3C3H3N4O)2]