Editing Rotaxane (section)

== Synthesis ==
The earliest reported synthesis of a rotaxane in 1967 relied on the [[statistical probability]] that if two halves of a dumbbell-shaped molecule were reacted in the presence of a [[macrocycle]] that some small percentage would connect through the ring.<ref>{{cite journal |title= Synthesis of a stable complex of a macrocycle and a threaded chain |year= 1967 |journal= [[J. Am. Chem. Soc.]] |volume= 89 |issue= 22 |pages= 5723–5724 |doi= 10.1021/ja00998a052 |last1= Harrison |first1= Ian Thomas. |last2= Harrison |first2= Shuyen. |bibcode= 1967JAChS..89.5723H }}</ref> To obtain a reasonable quantity of rotaxane, the macrocycle was attached to a [[solid-phase synthesis|solid-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 utilizing [[hydrogen bond]]ing, metal coordination, [[hydrophobic effect|hydrophobic forces]], [[covalent bond]]s, or [[Coulomb force|coulombic interactions]]. The three most common strategies to synthesize rotaxane are "capping", "clipping", and "slipping",<ref>{{Cite book |author= Aricó, F. |title= Templates in Chemistry II |chapter= Templated Synthesis of Interlocked Molecules |year= 2005 |journal= Topics in Current Chemistry |volume= 249 |pages= 203–259 |doi= 10.1007/b104330|isbn= 978-3-540-23087-8 |hdl= 10278/33611 }}</ref> though others do exist.<ref>{{cite journal |title= Threading-Followed-by-Shrinking Protocol for the Synthesis of a [2]Rotaxane Incorporating a Pd(II)-Salophen Moiety |year= 2004 |journal= [[J. Am. Chem. Soc.]] |volume= 126 |issue= 51 |pages= 16740–16741 |doi= 10.1021/ja0464490 |pmid= 15612709|last1= Yoon |first1= I |last2= Narita |first2= M |last3= Shimizu |first3= T |last4= Asakawa |first4= M }}</ref><ref>{{cite journal|title= A novel synthesis of chiral rotaxanes via covalent bond formation |year= 2004 |journal= [[Chem. Commun.]] |issue= 51 |pages= 466–467 |doi= 10.1039/b314744d |pmid= 14765261 |last1= Kameta |first1= N |last2= Hiratani |first2= K |last3= Nagawa |first3= Y }}</ref> 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.<ref>{{cite journal|title= 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 |year= 2007 |journal= [[J. Am. Chem. Soc.]] |volume= 129 |pages= 11950–11963 |doi= 10.1021/ja073513f |pmid= 17845039 |issue= 39 |last1= Aucagne |first1= V |last2= Berna |first2= J |last3= Crowley |first3= J. D. |last4= Goldup |first4= S. M. |last5= Hänni |first5= K. D. |last6= Leigh |first6= D. A. |last7= Lusby |first7= P. J. |last8= Ronaldson |first8= V. E. |last9= Slawin |first9= A. M. |last10= Viterisi |first10= A |last11= Walker |first11= D. B. }}</ref>

[[File:DNA origami rotaxanes.jpg|thumb|(a) A rotaxane is formed from an open ring (R1) with a flexible hinge and a dumbbell-shaped [[DNA origami]] structure (D1). The hinge of the ring consists of a series of strand crossovers into which additional [[thymine]]s are inserted to provide higher flexibility. Ring and axis subunits are first connected and positioned with respect to each other using 18 [[nucleotide]] 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 averaged [[Transmission electron microscopy|TEM]] 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.<ref>{{cite journal|doi=10.1038/ncomms12414|pmid=27492061|pmc=4980458|title=Long-range movement of large mechanically interlocked DNA nanostructures|journal=Nature Communications|volume=7|pages=12414|year=2016|last1=List|first1=Jonathan|last2=Falgenhauer|first2=Elisabeth|last3=Kopperger|first3=Enzo|last4=Pardatscher|first4=Günther|last5=Simmel|first5=Friedrich C.|bibcode=2016NatCo...712414L}}</ref>]]

===Capping===
[[File:Rotaxanes-synthesis-methods.png|thumb|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.<ref>{{cite web|url=https://www.youtube.com/watch?v=7o_-RiMRO6Y|website=youtube.com|title=Rotaxane by capping|date=10 March 2017 }}</ref>

===Clipping===
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 a [[ring closing reaction]] around the dumbbell-shaped molecule, forming the rotaxane.<ref>{{cite web|last1=Romero|first1=Antonio|title=Rotaxane by capping 3d|url=https://www.youtube.com/watch?v=7o_-RiMRO6Y|website=Rotaxane by capping 3d|date=10 March 2017 |publisher=3D video}}</ref>

===Slipping===
The method of slipping is one which exploits the thermodynamic<ref name="BrunsStoddart2016">{{cite book|author1=Carson J. Bruns|author2=J. Fraser Stoddart|title=The Nature of the Mechanical Bond: From Molecules to Machines|url=https://books.google.com/books?id=xShUDQAAQBAJ&pg=PA271|date=7 November 2016|publisher=John Wiley & Sons|isbn=978-1-119-04400-0|pages=271–}}</ref> 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 ===
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.

==="Active template" methodology===
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).