Functional nanomachines: Recent advances in synthetic molecular machinery

A mini-review: As the top-down approach for miniaturisation of technology reaches its inherent limitations, robust strategies to build nanoscale machinery components, which have the ability to convert an input energy into motion, from the molecular level up, become increasingly important. Nature is certainly the most proficient in the control of molecular level motion; nevertheless, many successes have been enjoyed in the pursuit of mimicking key aspects of nature’s molecular machines, including two state switches, ion pumps, unidirectional rotary motors and molecular robots that can move molecular cargo. This mini-review outlines of some of the most impressive recent examples towards this end.     

Cucurbit[7]uril‐Dimethyllysine Recognition in a Model Protein

Here, we provide the first structural characterization of host–guest complexation between cucurbit[7]uril ( Q7 ) and dimethyllysine (KMe₂) in a model protein. Binding was dominated by complete encapsulation of the dimethylammonium functional group. While selectivity for the most sterically accessible dimethyllysine was observed both in solution and in the solid state, three different modes of Q7 ‐KMe₂ complexation were revealed by X‐ray crystallography. The crystal structures revealed also entrapped water molecules that solvated the ammonium group within the Q7 cavity. Remarkable Q7 ‐protein assemblies, including inter‐locked octahedral cages that comprise 24 protein trimers, occurred in the solid state. Cucurbituril clusters appear to be responsible for these assemblies, suggesting a strategy to generate controlled protein architectures.     

Ground state sigmatropic and electrocyclic rearrangements in some monoterpenes: The pyrolysis of α-pinene

Alloocimene 7, obtained via ocimene 6 by heating α-pinene 2, was further pyrolysed to a complex mixture of products derived primarily from antarafacial 1,7- and suprafacial 1,5-hydrogen migrations, and 6-eleetron disrotatory electrocyclizations.     

Supramolecular recognition forces: an examination of weak metal-metal interactions in host-guest formation

Molecular receptors consisting of two parallel-disposed terpy-M-Cl units (M = Pd2+, Pt2+) are used to form host-guest adducts with aromatic molecules and with neutral square-planar Pt2+ complexes. Host-guest formation is controlled by several factors including pi-pi interactions and, in some cases, weak Pt-Pt interactions between the host and the guest. This latter interaction was examined by comparing the host-guest stability of adducts formed by isoelectronic Pt2+ and Au3+ complexes with the Pt2+ receptor. Consistently, the former is more stable.     

Total synthesis of the ristocetin aglycon

The first total synthesis of the ristocetin aglycon is described employing a modular and highly convergent strategy. An effective 12-step (12% overall) synthesis of the ABCD ring system 3 from its amino acid subunits sequentially features an intramolecular aromatic nucleophilic substitution reaction for formation of the diaryl ether and closure of the 16-membered CD ring system (65%), a respectively diastereoselective (3:1, 86%) Suzuki coupling for installation of the AB biaryl linkage on which the atropisomer stereochemistry can be further thermally adjusted, and an effective macrolactamization (51%) for closure of the 12-membered AB ring system. A similarly effective 13-step (14% overall) synthesis of the 14-membered EFG ring system 4 was implemented employing a room-temperature intermolecular S(N)Ar reaction of an o-fluoronitroaromatic for formation of the FG diaryl ether (69%) and a key macrolactamization (92%) with formation of the amide linking residues 1 and 2. The two key fragments 3 and 4 were coupled, and the remaining 16-membered DE ring system was closed via diaryl ether formation to provide the ristocetin tetracyclic ring system (15 steps, 8% overall) enlisting an unusually facile (25 degrees C, 8 h, DMF, >/=95%) and diastereoselective (>/=15:1) aromatic nucleophilic substitution reaction that benefits from substrate preorganization.     

Transport of organic solutes through amorphous teflon AF films

Fluorous media have great potential for selective extraction (e.g., as applied to organic synthesis). Fluorous polymer films would have significant advantages in fluorous separations. Stable films of Teflon AF 2400 were cast from solution. Films appear defect-free (SEM; AFM). Rigid aromatic solutes are transported (from chloroform solution to chloroform receiving phase) in a size-dependent manner (log permeability is proportional to -0.0067 times critical volume). Benzene's permeability is about 2 orders of magnitude higher than in comparable gas-phase experiments. The films show selectivity for fluorinated solutes in comparison to the hydrogen-containing control. Transport rates are dependent on the solvent making up the source and receiving phases. The effect of solvent is, interestingly, not due to changes in partition ratio, but rather it is due to changes in the solute diffusion coefficient in the film. Solvents plasticize the films. A less volatile compound, -COOH-terminated poly(hexafluoropropylene oxide) (4), plasticizes the films (T(g) = -40 degrees C). Permeabilities are decreased in comparison to 4-free films apparently because of decreased diffusivity of solutes. The slope of dependence of log permeability on critical volume is not changed, however.     

Synthesis of click‐reactive HPMA copolymers using RAFT polymerization for drug delivery applications

This study describes a versatile strategy combining reversible addition fragmentation transfer (RAFT) polymerization and click chemistry to synthesize well‐defined, reactive copolymers of N‐(2‐hydroxypropyl)methacrylamide (HPMA) for drug delivery applications. A novel azide containing monomer N‐(3‐azidopropyl)methacrylamide (AzMA) was synthesized and copolymerized with HPMA using RAFT polymerization to provide p(HPMA‐co‐AzMA) copolymers with high control of molecular weight (～10–54 kDa) and polydispersity (≤1.06). The utility of the side‐chain azide functionality by Cu(I)‐catalyzed azide‐alkyne cycloaddition (CuAAC) was demonstrated by efficient conjugation (up to 92%) of phosphocholine, a near infrared dye, and poly(ethylene glycol) (PEG) with different substitution degrees, either alone or in combination. This study introduces a novel and versatile method to synthesize well‐defined click‐reactive HPMA copolymers for preparing a panel of bioconjugates with different functionalities needed to systemically evaluate and tune the biological performance of polymer‐based drug delivery. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013 , 51, 5091–5099     

A Reduced-Symmetry Heterobimetallic [PdPtL4]4+ Cage: Assembly,Guest Binding,and Stimulus-Induced Switching

A strategy is presented that enables the quantitative assembly of a heterobimetallic [PdPtL₄]⁴⁺ cage. The presence of two different metal ions (Pd^II and Pt^II) with differing labilities enables the cage to be opened and closed selectively at one end upon treatment with suitable stimuli. Combining an inert Pt^II tetrapyridylaldehyde complex with a suitably substituted pyridylamine and Pd^II ions led to the assembly of the cage. ¹H and DOSY NMR spectroscopy and ESI mass spectrometry data were consistent with the quantitative formation of the cage, and the heterobimetallic structure was confirmed using single-crystal X-ray crystallography. The structure of the host–guest adduct with a 2,6-diaminoanthraquinone guest molecule was determined. Addition of N,N′-dimethylaminopyridine (DMAP) resulted in the formation of the open-cage [PtL₄]²⁺ compound and [Pd(DMAP)₄]²⁺ complex. This process could then be reversed, with the reformation of the cage, upon addition of p-toluenesulfonic acid (TsOH).