Arotaxane (from Latin rota'wheel' and axis'axle') is amechanically interlocked molecular architecture consisting of adumbbell-shaped molecule which is threaded through amacrocycle (see graphical representation). The two components of a rotaxane are kinetically trapped since the ends of the dumbbell (often calledstoppers) are larger than the internal diameter of the ring and preventdissociation (unthreading) of the components since this would require significant distortion of thecovalent bonds.
Much of the research concerning rotaxanes and other mechanically interlocked molecular architectures, such ascatenanes, has been focused on their efficientsynthesis or their utilization as artificialmolecular machines. However, examples of rotaxane substructure have been found in naturally occurringpeptides, including:cystine knot peptides,cyclotides or lasso-peptides such as microcin J25.
The earliest reported synthesis of a rotaxane in 1967 relied on thestatistical probability that if two halves of a dumbbell-shaped molecule were reacted in the presence of amacrocycle that some small percentage would connect through the ring.[2] To obtain a reasonable quantity of rotaxane, the macrocycle was attached to asolid-phase support and treated with both halves of the dumbbell 70 times and then severed from the support to give a 6% yield. However, the synthesis of rotaxanes has advanced significantly and efficient yields can be obtained by preorganizing the components utilizinghydrogen bonding, metal coordination,hydrophobic forces,covalent bonds, orcoulombic interactions. The three most common strategies to synthesize rotaxane are "capping", "clipping", and "slipping",[3] though others do exist.[4][5] Recently, Leigh and co-workers described a new pathway to mechanically interlocked architectures involving a transition-metal center that can catalyse a reaction through the cavity of a macrocycle.[6]
(a) A rotaxane is formed from an open ring (R1) with a flexible hinge and a dumbbell-shapedDNA origami structure (D1). The hinge of the ring consists of a series of strand crossovers into which additionalthymines are inserted to provide higher flexibility. Ring and axis subunits are first connected and positioned with respect to each other using 18nucleotide long, complementary sticky ends 33 nm away from the center of the axis (blue regions). The ring is then closed around the dumbbell axis using closing strands (red), followed by the addition of release strands that separate dumbbell from ring via toehold-mediated strand displacement. (b) 3D models and corresponding averagedTEM images of the ring and dumbbell structure. (c) TEM images of the completely assembled rotaxanes (R1D1). (d) 3D models, averaged and single-particle TEM images of R2 and D2, subunits of an alternative rotaxane design containing bent structural elements. The TEM images of the ring structure correspond to the closed (top) and open (bottom) configurations. (e) 3D representation and TEM images of the fully assembled R2D2 rotaxane. Scale bar, 50 nm.[7]
Rotaxane synthesis can be carried out via a "capping," "clipping, "slipping" or "active template" mechanism
Synthesis via the capping method relies strongly upon a thermodynamically driven template effect; that is, the "thread" is held within the "macrocycle" by non-covalent interactions, for example rotaxinations with cyclodextrin macrocycles involve exploitation of the hydrophobic effect. This dynamic complex or pseudorotaxane is then converted to the rotaxane by reacting the ends of the threaded guest with large groups, preventing disassociation.[8]
The clipping method is similar to the capping reaction except that in this case the dumbbell shaped molecule is complete and is bound to a partial macrocycle. The partial macrocycle then undergoes aring closing reaction around the dumbbell-shaped molecule, forming the rotaxane.[9]
The method of slipping is one which exploits the thermodynamic[10] stability of the rotaxane. If the end groups of the dumbbell are an appropriate size it will be able to reversibly thread through the macrocycle at higher temperatures. By cooling the dynamic complex, it becomes kinetically trapped as a rotaxane at the lower temperature.
Snapping involves two separate parts of the thread, both containing a bulky group. one part of the thread is then threaded to the macrocycle, forming a semi rotaxane, and end is closed of by the other part of the thread forming the rotaxane.
Leigh and co-workers recently began to explore a strategy in which template ions could also play an active role in promoting the crucial final covalent bond forming reaction that captures the interlocked structure (i.e., the metal has a dual function, acting as a template for entwining the precursors and catalyzing covalent bond formation between the reactants).
Animation of a pH-controlled molecular rotaxane shuttle
Rotaxane-based molecular machines have been of initial interest for their potential use inmolecular electronics as logicmolecular switching elements and asmolecular shuttles.[12][13] Thesemolecular machines are usually based on the movement of themacrocycle on the dumbbell. Themacrocycle can rotate around the axis of the dumbbell like a wheel and axle or it can slide along its axis from one site to another. Controlling the position of themacrocycle allows the rotaxane to function as a molecular switch, with each possible location of the macrocycle corresponding to a different state. These rotaxane machines can be manipulated both by chemical[14] and photochemical inputs.[15] Rotaxane based systems have also been shown to function as molecular muscles.[16][17] In 2009, there was a report of a "domino effect" from one extremity to the other in a Glycorotaxane Molecular Machine. In this case, the4C1 or1C4 chair-like conformation of the mannopyranoside stopper can be controlled, depending on the localization of the macrocycle.[18] In 2012, unique pseudo-macrocycles consisting of double-lasso molecular machines (also called rotamacrocycles) were reported in Chem. Sci. These structures can be tightened or loosened depending on pH. A controllable jump rope movement was also observed in these new molecular machines.[19]
Potential application as long-lasting dyes is based on the enhanced stability of the inner portion of the dumbbell-shaped molecule.[20][21] Studies withcyclodextrin-protected rotaxaneazo dyes established this characteristic. More reactivesquaraine dyes have also been shown to have enhanced stability by preventingnucleophilic attack of the inner squarainemoiety.[22] The enhanced stability of rotaxane dyes is attributed to the insulating effect of themacrocycle, which is able to block interactions with other molecules.
In a nanorecording application,[23] a certain rotaxane is deposited as aLangmuir–Blodgett film onITO-coated glass. When a positivevoltage is applied with the tip of ascanning tunneling microscope probe, the rotaxane rings in the tip area switch to a different part of the dumbbell and the resulting newconformation makes the molecules stick out 0.3nanometer from the surface. This height difference is sufficient for amemory dot. It is not yet known how to erase such a nanorecording film.
Accepted nomenclature is to designate the number of components of the rotaxane in brackets as a prefix.[24] Therefore, the a rotaxane consisting of a single dumbbell-shaped axial molecule with a single macrocycle around its shaft is called a [2]rotaxane, and twocyanostar molecules around the central phosphate group of dialkylphosphate is a [3]rotaxane.
^Yoon, I; Narita, M; Shimizu, T; Asakawa, M (2004). "Threading-Followed-by-Shrinking Protocol for the Synthesis of a [2]Rotaxane Incorporating a Pd(II)-Salophen Moiety".J. Am. Chem. Soc.126 (51):16740–16741.doi:10.1021/ja0464490.PMID15612709.
^Aucagne, V; Berna, J; Crowley, J. D.; Goldup, S. M.; Hänni, K. D.; Leigh, D. A.; Lusby, P. J.; Ronaldson, V. E.; Slawin, A. M.; Viterisi, A; Walker, D. B. (2007). "Catalytic "active-metal" template synthesis of [2]rotaxanes, [3]rotaxanes, and molecular shuttles, and some observations on the mechanism of the Cu(I)-catalyzed azide-alkyne 1,3-cycloaddition".J. Am. Chem. Soc.129 (39):11950–11963.doi:10.1021/ja073513f.PMID17845039.
^Stanier, Carol A.; o'Connell, Michael J.; Anderson, Harry L.; Clegg, William (2001). "Synthesis of fluorescent stilbene and tolan rotaxanes by Suzuki coupling".Chem. Commun. (5):493–494.doi:10.1039/b010015n.
^Schalley, C. A.; Beizai, K; Vögtle, F (2001). "On the Way to Rotaxane-Based Molecular Motors: Studies in Molecular Mobility and Topological Chirality".Acc. Chem. Res.34 (6):465–476.doi:10.1021/ar000179i.PMID11412083.
^Sauvage, J. P. (1999). "Transition Metal-Containing Rotaxanes and Catenanes in Motion: Toward Molecular Machines and Motors".ChemInform.30 (4): no.doi:10.1002/chin.199904221.
^Coutrot, F.; Busseron, E. (2009). "Controlling the Chair Conformation of a Mannopyranose in a Large-Amplitude [2]Rotaxane Molecular Machine".Chem. Eur. J.15 (21):5186–5190.doi:10.1002/chem.200900076.PMID19229918.
^Romuald, Camille; Ardá, Ana; Clavel, Caroline; Jiménez-Barbero, Jesús; Coutrot, Frédéric (2012). "Tightening or loosening a pH-sensitive double-lasso molecular machine readily synthesized from an ends-activated [c2]daisy chain".Chem. Sci.3 (6):1851–1857.doi:10.1039/C2SC20072D.hdl:10261/60415.
^Buston, Jonathan E. H.; Young, James R.; Anderson, Harry L. (2000). "Rotaxane-encapsulated cyanine dyes: enhanced fluorescence efficiency and photostability".Chem. Commun. (11):905–906.doi:10.1039/b001812k.
