Metallosupramolecular cages are an emerging, but as of yet relativity unexplored, drug delivery vector. Herein we show that discrete dipalladium(II) molecular cages of the formula [Pd₂L₄](X)₄ can be quantatively self-assembled from a simple tripyridyl ligand (2,6-bis(pyridin-3-ylethynyl)pyridine) and [Pd(CH₃CN)₄](X)₂ (X = BF₄ ⁻ or SbF₆ ⁻). The cages have been fully characterised using ¹H, ¹³C and DOSY NMR spectroscopy, elemental analysis, IR spectroscopy, and high resolution electrospray mass spectrometry (HR-ESMS). Additionally, the molecular structure of the [Pd₂L₄](SbF₆)₄ cage was confirmed unequivocally using X-ray diffraction. These [Pd₂L₄](X)₄ cages are stimuli-responsive and can be reversibly disassembled/reassembled upon the addition/removal of suitable competing ligands. The central cavities of the [Pd₂L₄](X)₄ cages are lined with four hydrogen bond accepting pyridine units which enable the encapsulation of two cisplatin molecules within the metallosupramolecular architecture through hydrogen bonding interactions between the cage and the amine ligands of the cisplatin guest. The structure of the [Pd₂L₄⊃(cisplatin)₂](BF₄)₄ host–guest adduct has been confirmed by ¹H NMR spectroscopy, HR-ESMS and X-ray crystallography. Additionally we have demonstrated that the cage–cisplatin host–guest adduct can be quantatively disassembled upon the addition of a competing ligand, releasing the cisplatin guest. This is the first crystallographically characterised example of a discrete metallosupramolecular cage encapsulating an FDA-approved inorganic drug molecule. This host–guest chemistry could open the way to relatively unexplored methods of drug delivery, which circumvent the malicious side effects and drug resistance associated with cisplatin and other anticancer therapeutics.

A family of thirteen tetranuclear heterometallic zinc(II)-lanthanide(III) complexes of the hexa-imine macrocycle (L^Pr)⁶⁻, with general formula Zn^II ₃Ln^III(L^Pr)(NO₃)₃·xsolvents (Ln = La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm or Yb), were prepared in a one-pot synthesis using a 3 : 1 : 3 : 3 reaction of zinc(II) acetate, the appropriate lanthanide(III) nitrate, the dialdehyde 1,4-diformyl-2,3-dihydroxybenzene (H₂L¹) and 1,3-diaminopropane. A hexanuclear homometallic zinc(II) macrocyclic complex [Zn₆(L^Pr)(OAc)₅(OH)(H₂O)]·3H₂O was obtained using a 2 : 0 : 1 : 1 ratio of the same reagents. A control experiment using a 1 : 0 : 1 : 1 ratio failed to generate the lanthanide-free [Zn₃(L^Pr)] macrocyclic complex. The reaction of H₂L¹ and zinc(II) acetate in a 1 : 1 ratio yielded the pentanuclear homometallic complex of the dialdehyde H₂L¹, [Zn₅(L¹)₅(H₂O)₆]·3H₂O. An X-ray crystal structure determination revealed [Zn₃ ^IIPr^III(L^Pr)(NO₃)₂(DMF)₃](NO₃)·0.9DMF has the large ten-coordinate lanthanide(III) ion bound in the central O₆ site with two bidentate nitrate anions completing the O₁₀ coordination sphere. The three square pyramidal zinc(II) ions are in the outer N₂O₂ sites with a fifth donor from DMF. Measurement of the magnetic properties of [Zn^II ₃Dy^III(L^Pr)(NO₃)₃(MeOH)₃]·4H₂O with a weak external dc field showed that it has a frequency-dependent out-of-phase component of ac susceptibility, indicative of slow relaxation of the magnetization (SMM behaviour). Likewise, the Er and Yb analogues are field-induced SMMs; the latter is only the second example of a Yb-based SMM. The neodymium, ytterbium and erbium complexes are luminescent in the solid phase, but only the ytterbium and neodymium complexes show strong lanthanide-centred luminescence in DMF solution.

The relevance of sub-picosecond protein motions to the catalytic event remains a topic of debate. Heavy enzymes (isotopically substituted) provide an experimental tool for bond-vibrational links to enzyme catalysis. A recent transition path sampling study with heavy purine nucleoside phosphorylase (PNP) characterized the experimentally observed mass-dependent slowing of barrier crossing (Antoniou, D.; Ge, X.; Schramm, V. L.; Schwartz, S. D. J. Phys. Chem. Lett.2012, 3, 3538). Here we computationally identify second-sphere amino acid residues predicted to influence the freedom of the catalytic site vibrational modes linked to heavy enzyme effects in PNP. We mutated heavy and light PNPs to increase the catalytic site vibrational freedom. Enzymatic barrier-crossing rates were converted from mass-dependent to mass-independent as a result of the mutations. The mutagenic uncoupling of femtosecond motions between catalytic site groups and reactants decreased transition state barrier crossing by 2 orders of magnitude, an indication of the femtosecond dynamic contributions to catalysis.