Halogen bonding and host-guest chemistry between N-alkylammonium resorcinarene halides, diiodoperfluorobutane and neutral guests

This is a sel -a chi ed e sion o an o iginal a icle. This e sion may di e om he o iginal in pagina ion and ypog aphic de ails. Au ho (s): Ti le: Yea : Ve sion: Copy igh : Righ s: Righ s u l: Please ci e he o iginal e sion: CC BY 4.0 h ps://c ea i ecommons.o g/licenses/by/4.0/ Halogen bonding and hos -gues chemis y be ween N-alkylammonium eso cina ene halides, diiodope luo obu ane and neu al gues s © 2019 Pan e al.; licensee Beils ein-Ins i u . Published e sion Pan, Fang ang; Dash i, Mohadeseh; Reynolds, Michael R.; Rissanen, Ka i; T an , John F.; Beyeh, Ngong Kodiah Pan, F., Dash i, M., Reynolds, M. R., Rissanen, K., T an , J. F., & Beyeh, N. K. (2019). Halogen bonding and hos -gues chemis y be ween N-alkylammonium eso cina ene halides, diiodope luo obu ane and neu al gues s. Beils ein Jou nal o O ganic Chemis y, 2019(15), 947-954. h ps://doi.o g/10.3762/bjoc.15.91 2019 947 Halogen bonding and hos –gues chemis y be ween N-alkylammonium eso cina ene halides, diiodope luo obu ane and neu al gues s Fang ang Pan*1, Mohadeseh Dash i2, Michael R. Reynolds2, Ka i Rissanen3, John F. T an *2 and Ngong Kodiah Beyeh*4 Full Resea ch Pape Open Access Add ess: 1College o Chemis y, Key Labo a o y o Pes icide & Chemical Biology o Minis y o Educa ion, Hubei In e na ional Scien i ic and Technological Coope a ion Base o Pes icide and G een Syn hesis, Cen al China No mal Uni e si y, Luoyu Road 152, Wuhan, Hubei P o ince, 430079, People's Republic o China, 2Uni e si y o Windso , Depa men o Chemis y and Biochemis y, Windso , On a io, 401 Sunse A enue, N9B 3P4, Canada, 3Uni e si y o Jy askyla, Depa men o Chemis y, PO Box 35, Jy äskylä, FIN-40014, Finland and 4Oakland Uni e si y, Depa men o Chemis y, 146 Lib a y D i e, Roches e , Michigan, 48309-4479, USA Email: Fang ang Pan* - [email p o ec ed]; John F. T an * - [email p o ec ed]; Ngong Kodiah Beyeh* - [email p o ec ed] * Co esponding au ho Keywo ds: capsule; dime ic assemblies; halogen bonding; hos –gues chemis y; eso cina ene sal s; X- ay c ys allog aphy Beils ein J. O g. Chem. 2019, 15, 947–954. doi:10.3762/bjoc.15.91 Recei ed: 04 Feb ua y 2019 Accep ed: 03 Ap il 2019 Published: 18 Ap il 2019 This a icle is pa o he hema ic issue "No el mac ocycles – and old ones doing new icks". Gues Edi o : W. Jiang © 2019 Pan e al.; licensee Beils ein-Ins i u . License and e ms: see end o documen . Abs ac Single c ys al X- ay s uc u es o halogen-bonded assemblies o med be ween hos N-hexylammonium eso cina ene b omide (1) o N-cyclohexylammonium eso cina ene chlo ide (2), and 1,4-diiodooc a luo obu ane and accompanying small sol en gues s (me h- anol, ace oni ile and wa e ) a e p esen ed. The gues s’ inclusion a ec s he geome y o he ca i y o he ecep o s 1 and 2, while he di alen halogen bond dono 1,4-diiodooc a luo obu ane de e mines he o e all na u e o he halogen bond assembly. The c ys al la ice o 1 con ains wo s uc u ally di e en dime ic assemblies A and B, o mally esul ing in he mix u e o a capsula dime and a dime ic pseudo-capsule. 1H and 19F NMR analyses suppo s he exis ence o hese halogen-bonded complexes and en- hanced gues inclusion in solu ion. 947 In oduc ion The cons uc ion o speci ic sup amolecula assemblies based on he di ec ional non-co alen bonding has been a cen al goal o sup amolecula chemis y and ma e ials science [1-3]. New sys ems bo h help us o be e unde s and he na u e and impe us behind he sel -assembly o hese ascina ing sys ems, while also p o iding new ma e ials ha can p o ide he basis Beils ein J. O g. Chem. 2019, 15, 947–954. 948 o a wide numbe o applica ions [4,5]. Halogen bonding (XB), as a ype o di ec ional non-co alen in e ac ion, is ega ded as he “long los b o he ” o hyd ogen bonding (HB) [6,7]. Al- hough XB in many aspec s is e y simila o HB, and in mos cases no as s ong as classical HB, he cha ac e o XB, such as hyd ophobici y, adjus abili y, o so ness, allows hese in e ac- ions o be used in aqueous o pola en i onmen s whe e HB-based sys ems a e less iable [8-12]. Howe e , we lack he analy ical ools o di ec ly examine and de e mine he p ecise s uc u e o XB assemblies in solu ion [13-15]. In he solid- s a e, X- ay di ac ion has p o en an inc edibly e ec i e ool o obse ing p i ileged con o ma ions and s uc u es [15-19]. F om he c ys allog aphic in o ma ion we can ex ac he poly- mo phism, high Z’- alue, wining, and diso de ha p o ide insigh in o he dynamics o p enuclea ion assembly, nuclea ion, and c ys al g ow h, which, in u n, p o ide in o ma ion ega ding he na u e o assemblies in solu ion [20-25]. In pa ic- ula , a high Z’- alue s uc u e is some imes ega ded as a “ ossil” o he solu e in solu ion, since he symme y indepen- den molecules ha e a g ea deal o in luence on he way in which he c ys als o m [26]. Twinning and diso de a e gene - ally seen as an undesi able complica ion in de e mining s uc- u es; howe e , he na u e and ex en o he diso de con ains signi ican in o ma ion ega ding he dynamics and con o ma- ional sampling o he molecules [19,24,27]. Desi aju e al. em- ploying subs i u ional diso de , achie ed he co-c ys alliza ion o six componen s [28]. As o posi ional diso de , i gene ally indica es he same molecule o assembly can adop mo e han one a ou able con o ma ion. F om his pe spec i e, diso de can be conside ed as a special case o a co-c ys al o high Z’- alue s uc u e. Diso de is no inhe en ly a ea u e o a poo s uc u e, diso de ins ead indica es he complexi y o he dynamic solu ion s a e. Sol ing i , howe e , emains a chal- lenge. N-Alkylammonium eso cina ene halides (NARXs) ha e been ex ensi ely s udied in ou g oups as mul iden a e halogen bond accep o s [29-34]. We ha e p e iously shown ha N-alkyl- ammonium eso cina ene b omides (NARB s) can o m a ious halogen-bonded assemblies wi h he classical o ganic halogen bond dono 1,4-diiodooc a luo obu ane (DIOFB) depending on he sol en , he p esence o po en ial gues s, and he leng h o he alkyl chain [30,31]. In ou p e ious epo , he basic con o - ma ion o he hos N-hexylammonium eso cina ene b omide (Hex-NARB ) was d i en by he inco po a ion o a 1,4-dioxane gues molecule [32], and he in e -ca i and b idging o DIOFB. The ela i ely long N-hexylammonium g oups endow he cons uc s wi h signi ican lexibili y. Thus, di e en s uc u es o he same XB accep o –dono pai could be ob ained by simply changing he sol en . The sol en does no appea o be c i ical o he halogen bonded assembly, and his aised he ques ion as o whe he c ys als a ising om sol en mix- u es could be use ul in p obing he sol a ion in e ac ions in solu ion. In he cu en s udy, we examine he ole o he inclusion gues in de e mining he inal XB s uc u es. Ins ead o adding 1,4- dioxane as a gues , we use me hanol and ace oni ile as bo h sol en and as po en ial inclusion gues s (Figu e 1). The lexi- bili y impa ed o he hos due o he lack o a de ined inclusion gues in hese sys ems is conside able and led o many amo - phous sys ems, as expec ed. Howe e , wo samples we e suc- cess ully c ys allized and s uc u ally cha ac e ized by single X- ay c ys allog aphy: MeOH-MeCN@1&DIOFB and Wa e @2&DIOFB. These wo s uc u es, besides illus a ing he po en ial o halogen bonding o o ganizing complex capsula sys ems, shed ligh on he impo ance o lexibili y in a ec ing he sel -assembled sys ems. Figu e 1: Te a alen XB accep o , Hex-NARB 1, Cy-NARCl 2, di a- len XB dono DIOFB, and gues s MeCN, MeOH and wa e . Resul s and Discussion Single c ys al X- ay di ac ion The endo-inclusion o gues s by NARXs g ea ly in luences he geome y o he sys em and di ec ly a ec s he o ien a ion o he uppe im a ms. This is pa icula ly ue o he NARX de- i a i es wi h long chain uppe im subs i uen s. We ha e p e i- ously obse ed ha e en wi h he mos sui able inclusion gues (1,4-dioxane), he la ice sol en molecules, ega dless o hei pola i y, inse be ween wo N-hexyl a ms using an OH/CH···B − hyd ogen bond (Figu e 2) [32]. To be e unde - s and whe he his is undamen al o hese sys ems, o a esul o he en o ced geome y caused by he included gues , we ha e ex ended his s udy in his cu en epo by excluding he 1,4- dioxane molecule as ob ious inclusion gues s. The newly isola ed c ys al, MeOH-MeCN@1&DIOFB, is o med as a 2:2 (1:DIOFB) halogen-bonded species encapsu- Beils ein J. O g. Chem. 2019, 15, 947–954. 949 Figu e 2: The p e iously epo ed halogen-bonded complexes CHCl3@1&DIOFB (a), and MeOH@1&DIOFB (b). (c)The i o 1,4-dioxane wi hin he ca i y o 1 [32]. la ing app oxima ely equimola amoun s o MeCN and MeOH in he ca i y o he eso cina enes. Signi ican diso de is p esen in his ca i y, iz, hal MeCN and hal MeOH we e assigned as diso de in he ca i y o 1. Acco ding o he p e i- ously epo ed s uc u e, when 1,4-dioxane was he inclusion gues , he olume o he ca i y is abo e 170 Å3, much la ge han ha o MeCN and MeOH, which a e ca. 41 and 53 Å3, e- spec i ely [35]. Hence, he eso cina ene has o de o m o adap o he small gues s by maximizing he con ac s be ween he hos and gues (Figu e 3). In de ail, in he MeCN occupied sys ems, he N a om is s abilized by an NH···N hyd ogen bond and a weak pnic ogen bond o a B − coun e ion wi h an RNB o 0.96 (Suppo ing In o ma ion File 1, Figu e S2). MeOH-s abilized sys ems ins ead employ weak NH···O and OH···N hyd ogen bonds (Suppo ing In o ma ion File 1, Figu e S2). In bo h cases, he elec on- ich en i onmen o he ca i y p o ides a nega i e elec os a ic su ace o in e ac ions wi h he elec oposi i e me hyl g oups o ei he MeCN o MeOH causing he o ien a- ion o be simila in bo h cases. De o ma ion o he eso - cina ene is a esul o he small sol en size leading o a de- c ease in in e nal ca i y olume o he ecep o . The calcula ed space sizes a e 79.45 Å3 in MeOH@1 and 101.17 Å3 in MeCN@1 ( p obe = 1.2 Å) [34]. The de o ma ion also shi s he ela i e posi ions o he N-alkyl “a ms” and he halide anions, which addi ionally change he ela i e o ien a ion o DIOFB XB dono s when di ec ional halogen bonding o ms. Two DIOFB linked wo MeOH-MeCN@1 complexes, simila o ha obse ed wi h ou p e ious chlo o o m-in ol ed 2:2 halogen- bonded complex [31]. In he p esen assembly, no sol en mole- cules a e ound in he encapsula ed olume ou lined by he wo DIOFB molecules and so he wo ca i ands could be assigned. The absence o he gues molecules, and he esul ing emp y space, induces diso de o bo h he hexyl g oups on he uppe - im o he ca i and, and he DIOFB molecules. Two p e e ed con o ma ions o hese sys ems we e iden i ied wi h a a io o ca. 3:1 (Figu e 3, Figu es S1 and S3 in Suppo ing In o ma ion File 1). Due o he cen e o in e sion, he wo con o ma ions show di e en dime iza ion modes (Suppo ing In o ma ion File 1, Figu e S3). In 1&DIOFB_A, he wo hex-NARB s a e linked by wo DIOFB molecules ia ou B ···I halogen bonds wi h a e age RXB o 0.86. The wo pa icipa ing b omide anions a e on adjacen “a ms”; he emaining wo B − coun e ions a e co e ed by he ben hexyl “a ms”. In 1&DIOFB_B, he wo DIOFB molecules link he wo hex-NARB s using he diame i- cally opposed B − anions. The a e age RXB o hese XBs is 0.98. In his second con o me , a space was c ea ed be ween he hos s, hus he hexyl g oups bend inwa ds o ill he space. The ela i ely s ong halogen bonds in 1&DIOFB_A pa ially accoun o i s la ge popula ion occupancy han 1&DIOFB_B. In bo h modes, he e is no sol en -accessible space be ween he dime ized eso cina ene sal s. The halogen bond dono s connec he wo eso cina ene like a solid ube, only c ea ing isola ed Beils ein J. O g. Chem. 2019, 15, 947–954. 950 Figu e 3: The wo dime iza ion modes in he MeOH-MeCN@1&DIOFB complex. In bo h modes, he ca i ies a e shown as anspa en yellow cloud. po es in he ca i y o he eso cina ene. No e ha he wo modes a e p esen simul aneously in he c ys al la ice, hus, he s uc u e o mally con ains a ound 75% halogen bonded dime , and 25% halogen bonded capsule. Addi ionally, he con o ma- ion di e ence could e eal he mo ion o he molecules in solu- ion, and he e apo a ion o he sol en molecules du ing c ys al g ow h. Wa ing o he hexyl g oups also a ec s one o he p opyl g oups in he lowe im o he eso cina ene. As a esul , he wo con o me s A and B also di e en ia e om each o he in he lowe im. A simila s udy was also ex ended o ano he eso cina ene chlo ide sal , Cy-NARCl 2. The ob ained c ys al showed he assembly as Wa e @2&DIOFB, o ming a 1:2 (2:DIOFB) halogen bonded chain (Figu e 4). In his case, he ca i and encapsula ed wo wa e molecules in he ca i y. The wa e mol- ecules we e posi ioned a he same le el as he (HNH···Cl−)4 HB ci cle. The O···Cl− dis ances o 3.13(3) and 3.22(4) Å sugges OH···Cl− hyd ogen bonds. Meanwhile, an OH···O hyd ogen bond should also exis be ween he wo wa e mole- cules wi h he O···O dis ance o 3.01(5) Å. I is su p ising o ind ha he eso cina ene ca i y below hese wa e molecules is emp y. I seems he elec onega i e su ace o he ca i y epels he wa e molecules and pushes hem up (Figu e 4). Besides he hyd ogen bonds, each Cl− anion also dona es elec- on densi y o one DIOFB molecule ia a halogen bond wi h an a e age RXB o 0.88. The ou DIOFB molecules bound wi h 2 can be classi ied in o wo g oups by i ue o hei di ec ion- ali y. Each g oup links o ano he eso cina ene chlo ide sal h ough an XB. The XB in e ac ions consequen ly o ganize he ca i ands along he c ys allog aphic c axis. This binding mode is di e en om all he o he epo ed halogen bonded assem- blies obse ed o NARXs. We accoun o he s agge ed connec ion in Wa e @2&DIOFB by he wis o he eso - cina ene amewo k ha esul s in he absence o a geome y- suppo ing inclusion gues . The p esence o he halogen bond dono s co e s he ca i y o he eso cina ene and c ea es a po e wi h olume o ca. 114.51 Å3 ( p obe = 1.2 Å). The wo encap- sula ed wa e molecules only ake up 33.9% o his po e, much lowe han he 55% ha would be expec ed based on Rebek’s ule [36]. NMR spec oscopy Sol en in e e ence is a key limi ing ac o in obse ing halogen bonds in solu ion. Despi e his limi a ion, NMR spec- oscopy is one o he mos powe ul ools o obse ing and s udying XB sys ems in solu ion [37-41]. The b omide anions o he NARB s a e hyd ogen-bonded o he hyd ogens o he Beils ein J. O g. Chem. 2019, 15, 947–954. 951 Figu e 4: (a) The halogen bonding (blue b oken lines), hyd ogen bonding ( ed b oken lines) and he hos –gues e ec (wa e molecules in CPK, and he ca i y space in anspa en yellow cloud) in Wa e @2&DIOFB; (b) The halogen bonded polyme . Wa e molecules in CPK mode and all he o he in ball-and-s ick ype. Figu e 5: 19F NMR in CDCl3 a 298 K o : a) DIOFB (10 mM); b) 1:2 mix u e o DIOFB and 1; 1:2:1 mix u e o DIOFB, 1, and c) MeCN, d) MeOH. The dashed lines gi e an indica ion o he signal changes in ppm, esul ing om he o ma ion o XBs. The dashed lines gi e an indica ion o he signal changes in ppm. ammonium g oups and o he phenolic hyd oxy g oups. Halides such as chlo ide and b omides can ha e high coo dina ion numbe s and as such can simul aneously be in ol ed in bo h HB and XB o o m o de ed assemblies [32,33]. When he al eady hyd ogen-bonded halides in NARXs a e in ol ed in XB, changes in he 1H NMR chemical shi s o he –OH and –NH2 p o ons o he NARXs a e expec ed [32,33]. Addi ional- ly, NARXs a e also known o coope a i ely bind small gues molecules such as mono- and diamides [42,43]. Consequen ly, we used 1H and 19F NMR spec oscopy o s udy he XB assem- blies o med be ween Hex-NARB 1 and 1,4-diiodooc a luo- obu ane (5) in he p esence o he sol en gues s (MeOH and MeCN) in chlo o o m. Fo his s udy, we p epa ed samples in- cluding he pu e componen s as well as h ee expe imen al mix- u es: a 1:2 mix u e o N-hexyl NARB 1 and XB dono DIOFB; and a 1:2:2 mix u e o hos , XB-dono , and ei he me hanol o ace oni ile. The 1H and 19F NMR spec a o all hese samples we e eco ded a 298 K and analyzed. In he 19F NMR analyses, he luo ine signals o he XB dono DIOFB we e moni o ed. In all cases, mino up ield shi s o he luo ines on he e minal ca bons we e obse ed (0.12 ppm in 1·DIOFB, 0.13 ppm in 1·DIOFB·MeOH and 1·DIOFB·MeCN, Figu e 5). Minimal changes (<0.03 ppm) we e obse ed o he Beils ein J. O g. Chem. 2019, 15, 947–954. 952 Figu e 6: 1H NMR in CDCl3 a 298 K o : a) 1 (10 mM), b) 1:2 mix u e o 1 and DIOFB, c) 1:2:1 mix u e o 1, DIOFB and MeOH, d) 1:1 mix u e o 1 and MeOH, and e) MeOH (10 mM). The dashed lines gi e an indica ion o he signal changes in ppm. The as e isk ep esen s he esidual CDCl3 sol en . luo ine a oms a ached o he in e nal ca bon a oms. This s ongly sugges s ha a simila XB in ol ing he iodine a oms o DIOFB exis s in solu ion bo h wi h and wi hou he gues s (Figu e 5). To complemen he di ec e idence om 19F NMR, 1H NMR showed small changes o he –OH and –NH2 signals o 1, a i- bu ed o he o ma ion o HB and XB in solu ion (Figu e 5 and Figu e S4 in Suppo ing In o ma ion File 1). In he p esence o he gues s (MeOH and MeCN), 1H NMR e eal signi ican complexa ion-induced shielding o he gues p o ons om sam- ples 1·DIOFB·MeOH and 1·DIOFB·MeCN. The e was a signi i- can inc ease in he shielding o he gues signals when com- pa ed o he hos :gues mix u es (1·MeOH and 1·MeCN). Taking he MeOH gues as an example, in he p esence o he XB dono DIOFB, he me hyl p o ons o MeOH mo e 0.27 ppm down ield compa ed o a mo e limi ed 0.12 ppm shi in he absence o he XB dono DIOFB (Figu e 6). In he halogen bonded assembly be ween DIOFB and 1, he DIOFB blocks he “side windows” o he NARX hus inc easing he dep h o he ca i y. As such he bound gues su e s an inc ease in he aniso opy in luence om he hos ’s a oma ic ings, in- c easing he shielding. Conclusion In conclusion, we p esen XB assemblies be ween Hex-NARB and Cy-NARCl as e a alen XB accep o s, a di alen XB dono DIOFB, and small o ganic gues sol en s (MeOH, MeCN and wa e ). In he assemblies, bo h XB and HB a e wo king in andem and conce edly o o m ne wo ks o non-co alen in e - ac ions s abilizing he dime ic and capsula s uc u es in he solid s a e. The inclusion gues s a ec he geome y o he ca i y o he hex-NARB and cy-NARCl, hus a ec ing he halogen bonding connec ion in he inal assemblies. In he com- plex MeOH-MeCN@1&DIOFB, because o he c ys allo- g aphic diso de , wo halogen bonded dime iza ion modes we e ound in he c ys al la ice. In he complex o Wa e @2&DIOFB, wo wa e molecules ac as inclusion gues s, aking up only 33.9% o he ca i y, hus he squeezed eso cina ene chlo ide p e e s o be polyme ized ia halogen bonds wi h DIOFB. The 1H NMR s udies in chlo o o m o Hex-NARB and DIOFB clea ly con i m he exis ence o XB in solu ion h ough easonable shi changes o he 19F signals o –CF2I and small chemical shi changes o he –OH and –NH2 signals. Gues binding was con i med om he inc ease shielding o he gues signals. These esul s adds o he li e a- u e o small o ganic gues compounds bound by N-alkylammo- nium eso cina ene halide ecep o s syne gis ically ia HB and XB in e ac ions. Suppo ing In o ma ion Suppo ing In o ma ion File 1 Expe imen al de ails, 1H and 19F NMR solu ion da a and X- ay c ys allog aphic de ails. [h ps://www.beils ein-jou nals.o g/bjoc/con en / supplemen a y/1860-5397-15-91-S1.pd ] Acknowledgemen s The au ho s g a e ully acknowledge he inancial suppo om Cen al China No mal Uni e si y, China, he Uni e si y o Windso , ON, Canada, he Uni e si y o Jy askyla, Finland, and Oakland Uni e si y, MI, USA. This wo k was suppo ed by he P og am o In oducing Talen s o Discipline o Uni e si- ies o China (111 p og am, B17019), he Na ional Na u al Beils ein J. O g. Chem. 2019, 15, 947–954. 953 Science Founda ion o China (NSFC, F.P.: g an no. 21602071), and he Fundamen al Resea ch Funds o he Cen al Uni e si- ies (F.P.: g an no. CCNU17QN006). ORCID® iDs Fang ang Pan - h ps://o cid.o g/0000-0002-3091-6795 Mohadeseh Dash i - h ps://o cid.o g/0000-0001-8200-1602 Michael R. Reynolds - h ps://o cid.o g/0000-0002-8723-930X Ka i Rissanen - h ps://o cid.o g/0000-0002-7282-8419 John F. T an - h ps://o cid.o g/0000-0002-4780-4968 Ngong Kodiah Beyeh - h ps://o cid.o g/0000-0003-3935-1812 Re e ences 1. Whi esides, G.; Ma hias, J.; Se o, C. Science 1991, 254, 1312–1319. doi:10.1126/science.1962191 2. Lehn, J.-M. Angew. Chem., In . Ed. Engl. 1988, 27, 89–112. doi:10.1002/anie.198800891 3. Chang, S. K.; Hamil on, A. D. J. Am. Chem. Soc. 1988, 110, 1318–1319. doi:10.1021/ja00212a065 4. 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