**1. Introduction**

The formation of enclosed cages, capable of gues<sup>t</sup> encapsulation, has been a mainstay of the supramolecular field since the early work on carcerands by Cram [1]. There has been particular attention given to the use of metal ions as structural agents in the formation of coordination cages, with their relatively predictable coordination geometries allowing for a good degree of control over the self-assembling synthesis [2–8]. The use of cages as agents for gues<sup>t</sup> discrimination is prevalent in the literature, with the internal cavities providing excellent size and shape discrimination between analytes. Such discrimination should lend itself well to separations of racemic mixtures and there is growing literature regarding the synthesis of chiral self-assembled cages [9–12].

There have been a number of different approaches towards chiral coordination cages reported in the literature, although far fewer than reports of achiral (or racemic) systems. Tetrahedralmetallo-supramolecular cages, with metal ions situated at the corners of the cage, can have tris-chelated octahedral metal centres that, by definition, have either Λ or Δ chirality with local C3 symmetry [13–15]. In the absence of any templating effect there is nothing to direct the chirality to a specific handedness and a mixture of cages with multiple diastereoisomers may result. Whilst this can provide a route to chiral cages using achiral precursors, it is clearly not the most desirable synthetic strategy, as the resolution of these complexes can be challenging. Similar approaches can be employed to make cages with other geometries, such as cubes and octahedra, with similar issues associated with the chirality of tris-chelate metal centres [16–20]. Rather than local chirality around metal centres, it is desirable that the chirality is communicated to the overall cage, including the interior cavity. Strategies towards this include the use of chiral ligands to connect the metals together [21–23] or using supplementary non-bridging chiral ligands that cap the metal centres [24–26]. The major synthetic difficulty of these routes is the

requirement for the ligands to be enantiomerically pure. There is also the issue that peripheral chiral groups, whilst reducing the symmetry of the cage as a whole, may not impact the interior space. One particularly relevant methodology has been to incorporate chiral functionalities at the ends of bis-chelate ligands, such that the molecular chirality dictates the Δ/Λ chirality around the resulting tris-chelated metal and therefore gives bulk enantiopurity in the cages [27–31]. Chiral coordination cages have recently been demonstrated to show enantioselective recognition [15,24], enantio- and chemo-selective catalysis [23,25], and recognition by fluorescence or luminescence methods [12]. Most pertinent to this current work are examples of using amino-acid based ligands to form chiral metallosupramolecular species containing copper paddlewheels, such as triangles and face-capped octahedra [32–34].

Recently we showed that it is possible to form charge-neutral, helical complexes of the form Cu4L4 containing two copper paddlewheel motifs and four dicarboxylate ligands containing amino acids, as shown in Figure 1 [35]. A similar, smaller cage complex was reported around the same time by Chen et al. [36], and many achiral analogues are known [37–42]. Subsequently we have explored how changing the nature of the dicarboxylate affects the type and size of cage that can be obtained. Using a more rigid naphthalenediimide-based ligand we, and others, isolated Cu12L12 octahedra [43,44] and, by using a more rotationally unrestricted biphenyl core, we obtained Cu8L8 "double-walled" squares [45]. It is also possible to isolate discrete catenanes using similar ligands [46], which are analogous to motifs observed in extended networks [47–50].

**Figure 1.** The previously reported chiral diacid (H2LeuBPSD) and its Cu4L4 cage complex alongside a schematic of the generic formulation of these helical cages, in which the cores of the ligands can be altered in attempts to construct analogous cages.

Herein we report the synthesis and structure of two enantiopure cages constructed using dicarboxylate ligands with different core groups, shown in Scheme 1. It is found that a longer, more curved ligand (**L1**2−) is able to form an analogue of the original Cu4L4 cage, whereas a shorter and less flexible ligand (**L2**2−) clearly shows strain and is unable to form a fully closed cage complex.

**Scheme 1.** Synthetic methodology for the two chiral diacids that have been used to synthesise cage complexes; the extended species **H2L1** and the shorter **H2L2**.

### **2. Materials and Methods**
