A Metallo-molecular Cage That Can Close the Apertures with

Mar 14, 2017 - Nishida , H.; Takada , N.; Yoshimura , M.; Sonoda , T.; Kobayashi , H. Bull. Chem. Soc. Jpn. 1984, 57, 2600– 2604 DOI: 10.1246/bcsj.5...
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A metallo-molecular cage that can close the apertures by coordination bonds Shigehisa Akine, Masato Miyashita, and Tatsuya Nabeshima J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.7b00840 • Publication Date (Web): 14 Mar 2017 Downloaded from http://pubs.acs.org on March 14, 2017

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A  metallo-­‐molecular  cage  that  can  close  the  apertures  by  coordina-­‐ tion  bonds     Shigehisa  Akine,*  a  Masato  Miyashita,b  and  Tatsuya  Nabeshima*  b     a

 Graduate  School  of  Natural  Science  and  Technology,  Kanazawa  University,  Kakuma-­‐machi,  Kanazawa  920-­‐1192,   b Japan;    Faculty  of  Pure  and  Applied  Sciences,  University  of  Tsukuba,  1-­‐1-­‐1  Tennodai,  Tsukuba,  Ibaraki  305-­‐8571,  Ja-­‐ pan     Supporting  Information  Placeholder ABSTRACT:   We   designed   a   novel   tricobalt(III)   metallo-­‐ molecular   cage   in   which   its   apertures   can   be   closed   with   bifunctional   ligands   via   coordination   bonds.   A   closed-­‐cage   complex   was   easily   formed   by   ligand   exchange   of   its   open-­‐ cage   analogue.   Guest   uptake/release   by   the   open-­‐cage   complex   was   sufficiently   fast   to   quickly   reach   guest-­‐binding   equilibrium,   while   that   by   the   closed-­‐cage   complex   was   extremely   slow   and   it   took   about   one   week   to   reach   equilibrium.  The  guest  uptake  was  retarded  by  at  least  2000   times  by  introduction  of  the  bifunctional  ligands  at  the  cage   apertures.  

Molecular   cages   have   attracted   much   attention   in   recent   years,  because  they  can  incorporate  smaller  molecules  in  the   1-­‐3 cavity  that  is  well  separated  from  the  outside  environment.   In   general,   molecular   cages   can   efficiently   wrap   guest   species   so   that   the   guest   uptake   and   release   are   slow   due   to   the   4 5 three-­‐dimensional   scaffold.   Carcerands   and   fullerenes   can   completely   imprison   the   guest   species;   the   incarcerated   guests  cannot  exit  the  cavity  without  destroying  the  capsular   structure.   In   fact,   whether   or   not   the   guest   species   are   en-­‐ trapped  permanently  depends  on  the  size  of  the  cage  portals   compared   to   the   guest   size.   Hemicarcerands,   which   have   a   larger   portal,   allow   some   guest   species   to   enter   and   exit   the   6 cavity.     While   complete   confinement   of   guest   species   is   of   interest   from   a   scientific   viewpoint,   nano-­‐sized   molecular   containers  that  can  close  their  aperture  depending  on  specif-­‐ ic  situations  would  be  advantageous  when  we  use  these  con-­‐ tainers   for   storing   and   transporting   functional   molecules   7 (Scheme  1a).    To  date,  some  gated   containers  have  been  de-­‐ veloped  for  controlling  the  guest  binding  processes  based  on   8 9 photo-­‐  and  redox  reactions.   We   focused   on   the   reversible   feature   of   metal–ligand   co-­‐ ordination   bonds,   which   allow   us   to   introduce   bifunctional   ligands  at  the  apertures  of  molecular  cages  to  control  enter-­‐ ing  of  the  guest  species  (Scheme  1b).    Since  the  bifunctional   ligands   have   to   be   introduced   without   destroying   the   cage   skeleton,   we   should   use   a   robust   cage   framework   that   can   remain   intact   under   the   conditions   for   coordination   bond   2 formation/cleavage.     In   this   context,   organic   cages   are   ad-­‐ vantageous   to   this   study   when   compared   to   coordination  

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cages.   The   tris(saloph)-­‐type   organic   cage   H6L,   which   we   previously  designed  for  the  synthesis  of  trinickel(II)  metallo-­‐ 11 host,   fulfills   the   requirement.     If   we   introduce   hexacoordi-­‐ 12 nate   metal   ions   into   its   saloph   tetradentate   sites,   we   can   introduce   two   additional   ligands   at   the   axial   positions   of   each   metal.     This   allows   us   to   introduce   a   bifunctional   ligand   at  each  aperture  of  the  molecular  cage  (Scheme  1c).    The  bi-­‐ functional   ligands   can   bridge   neighboring   metal   centers   to   close   the   aperture,   which   should   kinetically   suppress   the   guest  uptake.    We  now  report  a  novel  metallo-­‐molecular  cage   that   has   bifunctional   ligands   to   suppress   guest   molecules   passing  in  through  the  apertures.  

Scheme   1.   (a)   An   open   cage   that   can   close   the   aper-­‐ tures.   (b)   Concept   of   molecular   cage   that   can   close   the  aperture  by  coordination  of  bifunctional  ligands.   (c)  Design  of  metallo-­‐molecular  cage.  

  6 In   this   study,   we   used   the   low-­‐spin   d   cobalt(III)   ion,   which   generally   forms   hexacoordinate   inert   complexes   and   undergoes   very   slow   ligand   exchange.     This   would   enable  

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facile   introduction   of   the   diamine   ligand   that   is   firmly   fixed   at   the   apertures   of   the   molecular   cage   without   affecting   the   organic   cage   skeleton.     The   closed-­‐cage   trinuclear   complex   with   three   hda   (=   1,6-­‐hexanediamine)   ligands,   [LCo3(hda)3](OTf)3,   was   synthesized   in   92%   yield   by   the   complexation   of   H6L   with   cobalt(II)   acetate   in   air   in   the   1 presence   of   hda   ligand   (Scheme   2a;   Figures   S1–S3).   The   H   NMR   spectrum   showed   six   peaks   assignable   to   the   bridging   3+ hda   ligand   and   confirmed   the   1:3   stoichiometry   ([LCo3]   :   hda).     The   formation   of   discrete   species   [LCo3(hda)3](OTf)3   was   confirmed   by   ESI   mass   spectrometry   (m/z   =   709.8   for   3+ [LCo3(hda)3] ).     An   analogous   complex   [LCo3(oda)3](OTf)3,   which   have   three   longer   diamine   ligands   oda   (=   1,8-­‐ octanediamine),   was   similarly   synthesized   (Figures   S4,   S5).     However,   when   a   shorter   diamine   ligand   bda   (=   1,4-­‐ butanediamine)   was   used,   the   triply-­‐bridged   species   [LCo3(bda)3](OTf)3   was   not   obtained   (Figure   S6),   probably   because  the  bda  ligand  is  too  short  to  bridge  the  cobalt  ions   without  strain.    We  also  synthesized  the  open-­‐cage  analogue,   [LCo3(MeNH2)6](OTf)3,   in   a   similar   manner   in   87%   yield   as   the   control   compound   without   bifunctional   ligands   at   the   apertures   (Scheme   2b,   Figures   S7,   S8).   This   complex   has   six   methylamine  ligands  at  the  axial  positions  of  each  cobalt(III)   1 center.   The   structure   was   confirmed   by   H   NMR   spectro-­‐ scopy   and   mass   spectrometry   (ESI-­‐MS,   m/z   =   655.8   for   3+ [LCo3(MeNH2)6] ).  

membered  –(Co–NH2–(CH2)6–NH2)3–  macrocycle.    The  cavity   is   surrounded   by   two   pivotal   benzene   rings   in   parallel   (dis-­‐ tance  between  them  was  5.77  Å)  as  well  as  six  phenoxo  oxy-­‐ gen   atoms   forming   a   triangular   prism.     In   fact,   there   was   a   3+ water   molecule   in   the   cavity   of   [LCo3(hda)3]   in   the   crystal   structure.  

  3+

Figure   1.   Structure   of   [LCo3(hda)3]   in   the   crystal   of   [LCo3(hda)3](TFPB)3•2H2O•1.5MeOH.    (a,b)  ORTEP  drawings   (30%   probability   level).   The   methoxy   groups,   tert-­‐butyl   groups,   hydrogen   atoms,   and   the   minor   components   of   dis-­‐ ordered   atoms   are   omitted   for   clarity.   The   Co3(hda)3   27-­‐ membered   ring   is   colored   magenta.   (c,d)   Space   filling-­‐ models.   The   carbon   atoms   in   hda   ligands   are   colored   orange.   The   cross   section   view   is   shown   in   (d)   to   show   the   inside   cavity.  

Scheme   2.   Synthesis   and   structural   conversion   of   complexes.  

  It   is   noteworthy   that   the   aperture   of   this   open-­‐cage   com-­‐ 3+ plex  [LCo3(MeNH2)6]  can  be  easily  closed  by  a  reaction  with   the  bifunctional  ligands,  hda.  The  reaction  slowly  proceeded   with   the   concomitant   release   of   methylamine.     The   open-­‐ 3+ cage   complex   [LCo3(MeNH2)6]   was   almost   perfectly   con-­‐ 3+ verted  into  the  closed-­‐cage  complex,  [LCo3(hda)3]  (Scheme   1 2c),  which  was  confirmed  by   H  NMR  spectroscopy.   3+

The   X-­‐ray   crystallographic   analysis   of   [LCo3(hda)3]   re-­‐ vealed   a   cage-­‐like   structure   containing   three   octahedral   co-­‐ 13 balt(III)   ions.     Three   hda   ligands,   which   bridge   the   three   cobalt   ions,   are   effectively   blocking   the   apertures   to   give   a   closed-­‐cage   (Figure   1a,   c;   Figures   S19,   S20,   and   Table   S1).     Nevertheless,   there   should   remain   enough   space   for   guest   3+ inclusion  inside  the  cage  of  [LCo3(hda)3]  (Figure  1b,d)    The   three   cobalt(III)   ions   and   three   hda   ligands   constitute   a   27-­‐

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Prior   to   evaluating   the   effect   of  the   bifunctional   ligands   on   the   guest-­‐uptake   kinetics,   we   investigated   the   ion   recogni-­‐ tion   behavior   of   the   open-­‐cage   complex   + + + [LCo3(MeNH2)6](OTf)3  toward  alkali  metal  ions  (Na ,  K ,  Rb ,   + 14 1 Cs ;   TFPB   salts )   by   H   NMR   spectroscopy   (see   Figures   S13– + S17).     Upon   the   addition   of   Cs ,   a   new   set   of   signals   for   the   4+ inclusion   complex   [LCo3(MeNH2)6•Cs]   separately   appeared   3+ from   those   for   the   free   host   [LCo3(MeNH2)6] .     Obviously,   the  rate  of  guest  complexation  and  decomplexation  was  slow   1 on   the   H   NMR   timescale,   while   the   guest   inclusion   quickly   reached   equilibrium   on   the   laboratory   timescale   (within   5   min).     The   binding   constant   in   CD3OD   was   determined   to   be   –1 logKa  =  4.23  ±  0.06  (Ka  in  M )  (Table  1).    Based  on  these  data,   the   rate   constants   for   guest   binding   (k+,   k–)   were   roughly   –1 –1 –4 –1 estimated   as   follows:   k+   >   4   sec M ,   k–   >   2   ×   10   sec   (Scheme  3).  

Scheme  3.    

  In   fact,   we   had   expected   that   the   recognition   of   cationic   3+ guests  by  the  tricationic  host  [LCo3(MeNH2)6]  was  unfavor-­‐ able  due  to  a  strong  electrostatic  repulsion  between  the  posi-­‐ 4+ tive   charges.     However,   the   [LCo3(MeNH2)6•Cs]   complex   showed   an   unexpectedly   high   binding   constant,   which   was   + comparable  to  that  for  the  dibenzo-­‐24-­‐crown-­‐8/Cs  complex   15 under  similar  conditions.    This  strong  binding  between  the  

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cationic  species  can  be  explained  by  the  negatively  polarized   phenoxo   groups   that   can   bridge   two   or   more   metal   ions   as   16 17,18 seen  in  the  macrocyclic  and  helical  analogues.    The  trend   of  the  binding  constants  for  alkali  metal  ions  was  determined   + + + + to   be   Cs   >   Rb   >   K   >>   Na ,   clearly   indicating   the   preference   for   larger   ions.   The   selectivity   can   be   ascribed   to   the   rigid   host   framework,   which   is   well   preorganized   for   larger   ions   but  cannot  shrink  to  fit  smaller  guest  species.  

species   from   passing   in   and   out   through   the   apertures   (Scheme  1b)  as  expected  from  the  molecular  design.  

Table   1.   Association   constantsa   for   the   complexation   between  [LCo3(MeNH2)6](OTf)3  and  alkali  metal  ionsb.     –1

logKa  (M )  

Na+  

K+  

Rb+  

Cs+  

negligible  

2.89  ±  0.04  

3.70  ±  0.06  

4.23  ±  0.06  

a  Determined  by  NMR  spectroscopy  in  CD3OD  at  20  °C.  b   The   guests   were   added   as   a   TFPB   salt   (TFPB   =   tetrakis(3,5-­‐ bis(trifluoromethyl)phenyl)borate).   3+

+

Since  the  cage  framework  of  [LCo3]  showed  high  Rb  and   + Cs  affinities,  we  then  investigated  the  blocking  effect  of  the   diamine   ligands   in   the   closed-­‐cage   complex   [LCo3(hda)3](OTf)3   on   its   binding   kinetics   (see   Figures   S9– 1 S11).    The   H  NMR  spectrum  of  [LCo3(hda)3](OTf)3,  which  was   + recorded   1   h   after   the   addition   of   5   equiv   of   Cs ,   showed   only   + very   small   signals   (approximately   4%)   assignable   to   the   Cs   complex  (Figure  2a  i,  ii).    The  signal  slowly  grew  and  it  took   + approximately   50   h   for   the   40%   conversion   to   the   Cs   com-­‐ plex   (Figure   2b   i).     A   similar   slow   uptake   was   observed   for   + + Rb ,  but  the  conversion  to  the  Rb  complex  was  less  efficient   (Figure  2a  iii,  iv).    The  rate  constants  (k+,  k–)  for  the  second-­‐ order   equilibrium   reaction   of   the   guest   uptake   were   deter-­‐ mined   in   CD3OD   at   20   °C   from   the   analysis   of   the   time-­‐ course  of  the  mole  fractions  (Figure  2b,  Table  2).    It  is  note-­‐ worthy  that  the  uptake  rate  for  the  closed-­‐cage  complex  (k+  ~   –3 –1 –1 2   ×   10   M sec )   was   lower   by   at   least   2000   times   than   that   –1 –1 for   the   open-­‐cage   complex   (k+   >   4   M sec ).     The   guest   re-­‐ –6 –1 lease  of  the  closed-­‐cage  complex  (k–  ~  5  ×  10  sec )  was  also   significantly  retarded  compared  to  the  open-­‐cage  complex  (k–   –4 –1 ~  2  ×  10  sec ).    A  similar  deceleration  was  observed  for  the   + Rb  binding.       +

The  blocking  effect  of  the  hda  ligands  in  Cs  encapsulation   3+ by   [LCo3(hda)3]   was   also   evidenced   by   mass   spectrometry   (Figure   S18).   While   the   mass   spectrum   of   a   mixture   of   3+ + [LCo3(hda)3]   and   Cs   recorded   5   min   after   mixing   did   not   + show   any   peaks   for   Cs -­‐containing   species,   the   mass   spec-­‐ trum   after   24   h   exhibited   intense   peaks   at   m/z   =   565.5   for   4+ + [LCo3(hda)3•Cs] .     This   clearly   indicates   that   Cs   was   intro-­‐ + duced   into   an   environment   where   the   uptake/release   of   Cs   3+ by   [LCo3(hda)3]   was   significantly   retarded.   This   result   + strongly   suggests   the   encapsulation   of   Cs   into   the   cavity   of   3+ [LCo3(hda)3]   and   confirmed   the   blocking   effect   of   the   hda   + ligands  that  retard  uptake/release  of  Cs .    Probably,  the  guest   uptake/release  took  place  via  partial  dissociation  mechanism,   because  the  diamine  molecules  are  completely  occupying  the   + cage   portals.     The   Cs   ion   was   encapsulated   almost   at   the   center  of  the  cavity,  which  was  suggested  by  DFT  calculation.   It  is  noteworthy  that  the  dimension  of  the  cavity  did  not  sig-­‐ + nificantly   change   after   inclusion   of   Cs ,   indicating   that   the   3+ + cavity  of  [LCo3(hda)3]  is  well  preorganized  for  Cs  inclusion.     + Probably,   the   Cs   ion   binding   is   driven   by   cation-­‐π   interac-­‐ tions  with  the  two  pivotal  benzene  rings  as  well  as  the  coor-­‐ dination   of   the   phenoxo   groups.     Consequently,   the   bifunc-­‐ tional   ligands,   1,6-­‐hexanediamine,   efficiently   block   guest  

  1

Figure   2.  (a)   H  NMR  spectral  changes  of  [LCo3(hda)3](OTf)3   after   the   addition   of   metal   ions   at   20   °C   in   CD3OD,   [[LCo3(hda)3](OTf)3]  =  0.5  mM,  [MTFPB]  =  2.5  mM,  400  MHz.   Signals   indicated   by   black   circles   are   assigned   to   the   inclusion   complexes.   (b)   Changes   in   the   mole   fractions   of   3+ 4+ [LCo3(hda)3]  and  [LCo3(hda)3•M]  in  CD3OD  after  the  addi-­‐ + + tion  of  5  equiv  of  metal  ions:  (i)  Cs ,  (ii)  Rb .    

Table   2.   Rate   constants   and   association   constantsa   for   the   complexation   between   [LCo3(diamine)3]3+   (diamine  =  hda,  oda)  and  alkali  metal  ions  (Rb+,  Cs+).     guest   k+  (M–1sec–1)  

host   3+

+

k–  (sec–1)   –4

Ka  (M–1)   –5

[LCo3(hda)3]   Rb  

(8.0  ±  0.6)  ×  10  

[LCo3(hda)3]3+   Cs+  

(2.02  ±  0.05)  ×  10–3   (4.9  ±  0.2)  ×  10–6  

3+

+

[LCo3(oda)3]   Cs  

–3

(1.45  ±  0.04)  ×  10  

(1.20  ±  0.10)  ×  10  

67   410  

–5

(1.04  ±  0.07)  ×  10   140  

a  Determined  by  NMR  spectroscopy  in  CD3OD  at  20  °C.   Interestingly,   the   length   in   the   bridging   diamine   has   sig-­‐ nificant  influence  on  the  guest  binding  kinetics  and  binding   strength.     When   longer   bifunctional   ligand   oda   was   intro-­‐ duced,  the  guest  uptake  rate  decreased  by  ca.  30%  (Table  2;   Figure   S12).     It   is   noteworthy   that   the   association   constants   3+ + for   [LCo3(oda)3]   with   Cs   became   almost   1/3   of   that   for   3+ [LCo3(hda)3] .   Thus,   the   increased   number   of   methylene   groups  at  the  aperture  has  an  influence  on  the  uptake/release   rates  and  the  binding  constant.       In  conclusion,  we  have  designed  a  novel  metallo-­‐molecular   cage   to   which   we   can   introduce   bifunctional   ligands   at   the   3+ apertures.     Both   the   open-­‐cage   complex   [LCo3(MeNH2)6]   3+ + and   close-­‐cage   complex   [LCo3(hda)3]   showed   a   Cs -­‐ 3+ selectivity,   but   the   hda   ligands   in   [LCo3(hda)3]   effectively  

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block  the  guest  uptake  by  more  than  three  orders  of  magni-­‐ tude.   The   concept   of   the   open-­‐close   feature   in   this   system   would   be   applied   to   a   molecular   container   in   which   the   en-­‐ trapped   molecules   can   be   released   when   required.   Such   an   on-­‐demand  catch  and  release  of  guest  species  would  be  use-­‐ ful  for  molecular  functions  such  as  drug  delivery  and  chemi-­‐ cal  information  relay  systems.  

ASSOCIATED  CONTENT     Supporting  Information   Synthetic   procedure   and   the   characterization   data,   com-­‐ plexation   studies,   and   crystallographic   analysis   of   [LCo3(hda)3](TFPB)3.  This  material  is  available  free  of  charge   via  the  internet  at  http://pubs.acs.org.    

AUTHOR  INFORMATION   Corresponding  Author   [email protected]­‐u.ac.jp;  [email protected]  

ACKNOWLEDGMENT     This   work   was   supported   in   part   by   JSPS   KAKENHI   (Grant   Number   JP16H06510   (Coordination   Asymmetry)   and   JP26288022)   and   Kanazawa   University   CHOZEN   Project.   This  paper  is  dedicated  to  Professor  Takayuki  Kawashima  on   the  occasion  of  his  70th  birthday.  

REFERENCES   (1)  (a)  MacGillivray,  L.R.;  Atwood,  J.L.  Angew.  Chem.  Int.  Ed.  1999,   38,  1018–1033.  (b)  Steed,  J.  W.;  Atwood,  J.  L.  Supramolecular  Chemis-­‐ try,  Concept  and  Perspectives;  Wiley:  Chichester,  U.K.,  2000.   (2)   For   reviews   on   organic   cages,   see:   (a)   Holst,   J.R.;   Trewin,   A.;   Cooper,   A.I.   Nat.   Chem.   2010,   2,   915–920.   (b)   Mastalerz,   M.   Angew.   Chem.   Int.   Ed.  2010,  49,  5042–5053.  (c)  Cooper,  A.I.  Angew.   Chem.   Int.   Ed.   2011,   50,   996–998.   (d)   Nishiyabu,   R.;   Kubo,   Y.;   James,   T.D.;   Fossey,   J.S.   Chem.   Commun.   2011,   47,   1124–1150.   (e)   Zhang,   G.;   Mastalerz,   M.   Chem.   Soc.   Rev.   2014,   43,   1934–1947.   (f)   Huang,   S.-­‐L.;   Jin,  G.-­‐X.;  Luo,  H.-­‐K.;  Hor,  T.S.A.  Chem.   Asian   J.  2015,  10,  24-­‐42.  (g)   Evans,  J.D.;  Sumby,  C.J.;  Doonan,  C.J.  Chem.   Lett.  2015,  44,  582–588.   (h)  Briggs,  M.E.;  Cooper,  A.I.  Chem.  Mater.  2017,  29,  149–157.   (3)  For  reviews  on  coordination  cages,  see:  (a)  Stang,  P.J.;  Olenyuk,   B.  Acc.  Chem.  Res.  1997,  30,  502-­‐518.  (b)  Caulder,  D.L.;  Raymond,  K.N.   Acc.   Chem.   Res.   1999,   32,   975-­‐982.   (c)   Seidel,   S.R.;   Stang,   P.J.   Acc.   Chem.  Res.  2002,   35,  972-­‐983.  (d)  Fiedler,  D.;  Leung,  D.H.;  Bergman,   R.G.;  Raymond,  K.N.  Acc.   Chem.   Res.  2005,  38,  351-­‐360.  (e)  Fujita,  M.;   Tominaga,   M.;   Hori,   A.;   Therrien,   B.   Acc.   Chem.   Res.   2005,   38,   371-­‐ 380.   (f)   Koblenz,   T.S.;   Wassenaar,   J.;   Reek,   J.N.H.   Chem.   Soc.   Rev.   2008,  37,  247–262.  (g)  Dalgarno,  S.J.;  Power,  N.P.;  Atwood,  J.L.  Coord.   Chem.   Rev.   2008,   252,   825–841.   (h)   Tranchemontagne,   D.J.;   Ni,   Z.;   O’Keeffe,  M.;  Yaghi,  O.M. Angew.  Chem.  Int.  Ed.  2008,  47,  5136–5147.   (i)  Yoshizawa,  M.;  Klosterman,  J.K.;  Fujita,  M.  Angew.  Chem.  Int.  Ed.   2009,   48,   3418–3438.   (j)   Northrop,   B.H.;   Zheng,   Y.-­‐R.;   Chi,   K.-­‐W.;   Stang,   P.J.   Acc.   Chem.   Res.   2009,   42,   1554–1563.   (k)   Wiester,   M.J.;   Ulmann,  P.A.;  Mirkin,  C.A.  Angew.   Chem.   Int.   Ed.  2011,  50,  114–137.  (l)   Inokuma,  Y.;  Kawano,  M.;  Fujita,  M.  Nature   Chem.  2011,  3,  349–358.   (m)  Chakrabarty,  R.;  Mukherjee,  P.S.;  Stang,  P.J.  Chem.  Rev.  2011,  111,   6810–6918.  (n)  Cook,  T.R.;  Zheng,  Y.-­‐R.;  Stang,  P.J.  Chem.   Rev.  2013,   113,  734−777.  (o)  Smulders,  M.M.J.;  Riddell,  I.A.;  Browne,  C.;  Nitschke,   J.R.  Chem.   Soc.   Rev.  2013,  42,  1728-­‐1754.  (p)  Ward,  M.D.;  Raithby,  P.R.   Chem.   Soc.   Rev.  2013,  42,  1619-­‐1636.  (q)  Harris,  K.;  Fujita,  D.;  Fujita,  M.   Chem.   Commun.   2013,   49,   6703-­‐6712.   (r)   Han,   M.;   Engelhard,   D.M.;   Clever,  G.H.  Chem.  Soc.  Rev.,  2014,  43,  1848-­‐1860.  (s)  McConnell,  A.J.;   Wood,   C.S.;   Neelakandan,   P.P.;   Nitschke,   J.R.   Chem.   Rev.   2015,   115,   7729–7793.  

Page 4 of 11

(4)   (a)   Cram,   D.J.   Nature   1992,   356,   29-­‐36.   (b)   Cram,   D.J.;   Cram,   J.M.   Container   Molecules   and   Their   Guests.   Monographs   in   Su-­‐ pramolecular   Chemistry,  ed.  J.F.  Stoddart  (RSC,  Cambridge,  1994).  (c)   Jasat,  A.;  Sherman,  J.C.  Chem.  Rev.  1999,  99,  931-­‐967.   (5)  (a)  Murata,  M.;  Murata,  Y.;  Komatsu,  K.  Chem.   Commun.,  2008,   6083–6094.  (b)  Yamada,  M.;  Akasaka,  T.;  Nagase,  S.  Acc.  Chem.  Res.   2010,   43,   92-­‐102.   (c)   Gan,   L.;   Yang,   D.;   Zhang,   Q.;   Huang,   H.   Adv.   Mater.  2010,  22,  1498–1507.  (d)  Vougioukalakis,  G.C.;  Roubelakis,  M.   M.;   Orfanopoulos,   M.   Chem.   Soc.   Rev.   2010,   39,   817–844.   (e)   Ro-­‐ dríguez-­‐Fortea,  A.;  Balch,  A.L.;  Poblet,  J.M.  Chem.  Soc.  Rev.  2011,  40,   3551–3563.  (f)  Popov,  A.A.;  Yang,  S.;  Dunsch,  L.  Chem.  Rev.,  2013,  113,   5989−6113.   (6)  Warmuth,  R.;  Yoon,  J.  Acc.  Chem.  Res.  2001,  34,  95-­‐105.   (7)  (a)  Rieth,  S.;  Hermann,  K.;  Wang,  B.-­‐Y.;  Badjić,  J.D.  Chem.  Soc.   Rev.  2011,  40,  1609–1622.  (b)  Liu,  F.;  Wang,  H.;  Houk,  K.N.  Sci.  China   Chem.   2011,   54,   2038-­‐2044.   (c)   Liu,   F.;   Wang,   H.;   Houk,   K.N.   Curr.   Org.  Chem.  2013,  17,  1470-­‐1480.  (d)  Liu,  F.;  Helgeson,  R.C.;  Houk,  K.N.   Acc.  Chem.  Res.  2014,  47,  2168-­‐2176.  (e)  Hermann,  K.;  Ruan,  Y.;  Har-­‐ din,  A.M.;  Hadad,  C.M.;  Badjić,  J.D.  Chem.  Soc.  Rev.  2015,  44,  500-­‐514.   (8)  (a)  Piatnitski,  E.L.;  Deshayes,  K.D.  Angew.  Chem.  Int.  Ed.  1998,   37,  970-­‐972.  (b)  Wang,  H.;  Liu,  F.;  Helgeson,  R.C.;  Houk,  K.N.  Angew.   Chem.  Int.  Ed.  2013,  52,  655–659.   (9)   (a)   Nabeshima,   T.;   Furusawa,   H.;   Yano,   Y.   Angew.   Chem.   Int.   Ed.  1994,  33,  1750-­‐1751.  (b)  Helgeson,  R.C.;  Hayden,  A.E.;  Houk,  K.N.  J.   Org.  Chem.  2010,  75,  570–575.   (10)  For  a  metallo-­‐molecular  cage  with  guanidinium  caps,  see:  (a)   Zarra,   S.;   Smulders,   M.M.J.;   Lefebvre,   Q.;   Clegg,   J.K.;   Nitschke,   J.R.   Angew.   Chem.   Int.   Ed.  2012,  51,  6882–6885.  (b)  Zarra,  S.;  Wood,  D.M.;   Roberts,  D.A.;  Nitschke,  J.R.  Chem.  Soc.  Rev.  2015,  44,  419-­‐432.     (11)   (a)   Akine,   S.;   Miyashita,   M.;   Piao,   S.;   Nabeshima,   T.   Inorg.   Chem.  Front.  2014,  1,  53–57.  For  a  related  complex,  see:  (b)  Akine,  S.;   Piao,   S.;   Miyashita,   M.;   Nabeshima,   T.   Tetrahedron   Lett.   2013,   54,   6541–6544.   (12)  (a)  Bigotto,  A.;  Costa,  G.;  Mestroni,  G.;  Pellizer,  G.;  Puxeddu,   A.;   Reisenhofer,   E.;   Stefani,   L.;   Tauzher,   G.   Inorg.   Chim.   Acta   1970,   41-­‐49.   (b)   Shimakoshi,   H.;   Takemoto,   H.;   Aritome,   I.;   Hisaeda,   Y.   Tetrahedron  Lett.  2002,  43,  4809–4812.  (c)  Shimakoshi,  H.;  Takemoto,   T.;  Aritome,  I.;  Hisaeda,  Y.  Inorg.  Chem.  2005,  44,  9134–9136.   (13)   Crystallographic   data   for   [LCo3(hda)3](TFPB)3•2H2O•   1.5MeOH:   (C217.5H196B3Co3F72N12O15.5   =   4803.08),   triclinic,   space   group   – P1,   a   =   19.2543(4)   Å,   b   =   20.7309(4)   Å,   c   =   29.5488(6)   Å,   α   =   85.8030(10)   deg,   β   =   82.6610(10)   deg,   γ   =   74.2470(10)   deg,   V   =   3 –1 11249.5(4)  Å ,  Z  =  2,  T  =  120  K,  Dcalcd  =  1.418  g  cm ,  µ(Mo  Kα)  =  0.340   –1 mm ,  81717  reflections,  50235  unique  (Rint  =  0.0430),  R1  =  0.0791  (I  >   2σ(I)),  wR2  =  0.2166  (all  data).   (14)  Nishida,  H.;  Takada,  N.;  Yoshimura,  M.;  Sonoda,  T.;  Kobaya-­‐ shi,  H.  Bull.  Chem.  Soc.  Jpn.  1984,  57,  2600–2604.   (15)  Takeda,  Y.;  Yano,  H.  Bull.  Chem.  Soc.  Jpn.  1980,  53,  1720–1722.   (16)   (a)   Akine,   S.;   Sunaga,   S.;   Taniguchi,   T.;   Miyazaki,   H.;   Na-­‐ beshima,  T.  Inorg.   Chem.  2007,  46,  2959-­‐2961.(b)  Akine,  S.;  Utsuno,   F.;  Nabeshima,  T.  Chem.   Commun.  2010,  46,  1029-­‐1031.  (c)  Akine,  S.;   Utsuno,   F.;   Piao,   S.;   Orita,   H.;   Tsuzuki,   S.;   Nabeshima,   T.   Inorg.   Chem.  2016,  55,  810–821.   (17)  (a)  Akine,  S.;  Taniguchi,  T.;  Nabeshima,  T.  Angew.  Chem.  Int.   Ed.   2002,   41,   4670-­‐4673.   (b)   Akine,   S.;   Taniguchi,   T.;   Saiki,   T.;   Na-­‐ beshima,  T.  J.  Am.  Chem.  Soc.  2005,  127,  540-­‐541.  (c)  Akine,  S.;  Tani-­‐ guchi,  T.;  Nabeshima,  T.  J.  Am.  Chem.  Soc.  2006,  128,  15765-­‐15774.  (d)   Akine,  S.;  Sairenji,  S.;  Taniguchi,  T.;  Nabeshima,  T.  J.  Am.  Chem.  Soc.   2013,  135,  12948–12951.   (18)   For   reviews,   see:   (a)   Akine,   S.;   Nabeshima,   T.   Dalton   Trans.   2009,   10395-­‐10408.   (b)   Akine,   S.   J.   Inclusion   Phenom.   Macrocycl.   Chem.   2012,   72,   25-­‐54.   (c)   Akine,   S.   Patai's   Chemistry   of   Functional   Groups  edited  by  Marek,  I,  John  Wiley  and  Sons,  Ltd:  Chichester,  UK   2016.  doi:10.1002/9780470682531.PAT0909.    

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Graphical abstract Graphical abstract 40x19mm (600 x 600 DPI)

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Figure 1 Figure 1 69x58mm (600 x 600 DPI)

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Figure 2 Figure 2 106x135mm (600 x 600 DPI)

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Scheme 1 Scheme 1 86x92mm (600 x 600 DPI)

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Scheme 2 Scheme 2 67x55mm (600 x 600 DPI)

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Scheme 3 Scheme 3 9x1mm (600 x 600 DPI)

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