gels Review Carbocycle-Based Organogelators: Influence of Chirality and Structural Features on Their Supramolecular Arrangements and Properties Rosa M. Ortuño Departament de Química, Universitat Autònoma de Barcelona, 08193 Cerdanyola del Vallès, Spain; rosa.ortuno@uab.es Abstract: The rational design and engineer of organogel-based smart materials and stimuli-responsive materials with tuned properties requires the control of the non-covalent forces driving the hierarchical self-assembly. Chirality, as well as cis/trans relative configuration, also plays a crucial role promoting the morphology and characteristics of the aggregates. Cycloalkane derivatives can provide chiral chemical platforms allowing the incorporation of functional groups and hydrophobic structural units able for a convenient molecular stacking leading to gels. Restriction of the conformational freedom imposed by the ring strain is also a contributing issue that can be modulated by the inclusion of flexible segments. In addition, donor/acceptor moieties can also be incorporated favoring the interactions with light or with charged species. This review offers a perspective on the abilities and properties of carbocycle-based organogelators starting from simple cycloalkane derivatives, which were the key to establish the basis for an effective self-assembling, to sophisticated polycyclic  compounds with manifold properties and applications.  Citation: Ortuño, R.M. Keywords: low-molecular-weight organogelators; cycloalkanes; cholesterol-based organogelators; Carbocycle-Based Organogelators: chirality; stimuli-responsive materials; self-healing gels Influence of Chirality and Structural Features on Their Supramolecular Arrangements and Properties. Gels 2021, 7, 54. https://doi.org/10.3390/ 1. Introduction gels7020054 Nowadays, the applications of organogels as soft materials are huge in several areas. They include rationally designed gels for use in drug formulation and development [1], Academic Editor: Jean-Michel Guenet drug release [2], medical applications [3], encapsulation and controlled flavor and fragrance release [4], pollutants removal [5], supramolecular electronics [6], materials for bioinspired Received: 30 March 2021 Accepted: 26 April 2021 catalysis [7], selective agents for anion recognition [8,9], materials for eco-friendly oil Published: 1 May 2021 spill recovery [10–12] and products with manifold properties such as tissue regeneration materials, biosensors, cosmetics and lubricants, among other applications [13–15]. Publisher’s Note: MDPI stays neutral The design of low-molecular-weight organogelators (LMWOGs) with specific proper- with regard to jurisdictional claims in ties and targeted functions has been a real challenge for a highly active research field during published maps and institutional affil- the last 20 years and remains far from generalization [16–18]. The control of the driving iations. forces involved in self-assembling of organogelator molecules, i.e., hydrogen bonding and other non-covalent interactions such as van der Waals, π–π, dipolar and Coulomb interactions, is crucial to achieve hierarchically ordered architectures. In addition, chirality plays a key role in the formation of aggregates [19,20]. In addition, precise correlation of Copyright: © 2021 by the author. the non-covalent interactions with bulk properties and corresponding functions allows to Licensee MDPI, Basel, Switzerland. engineer smart materials [21] and multi-stimuli responsive materials [22–26]. This article is an open access article Carbocyclic rings can act as chemical platforms bearing suitable functional groups, distributed under the terms and such as amide, urea or amino acid, which are able to form hydrogen bonds, as well as conditions of the Creative Commons long alkyl chains or aromatic systems favoring molecular stacking. Furthermore, in these Attribution (CC BY) license (https:// molecules, chirality, in conjunction with conformational restriction due to the ring strain, is creativecommons.org/licenses/by/ a powerful tool to promote and direct the aforementioned interactions leading to aggregates 4.0/). with specific characteristics. Gels 2021, 7, 54. https://doi.org/10.3390/gels7020054 https://www.mdpi.com/journal/gels long alkyl chains or aromatic systems favoring molecular stacking. Furthermore, in these molecules, chirality, in conjunction with conformational restriction due to the ring strain, is a powerful tool to promote and direct the aforementioned interactions leading to aggre- gates with specific characteristics. Gels 2021, 7, 54 In this review, a perspective from highly relevant forerunner works till very 2 of 24recent results that deal with the gelling ability and self-assembling of carbocycle-based organo- gelators is afforded. The role of the chirality in the monomers and in the aggregates is emphasized. Special In this review, attention has a perspective been from paidrelevant highly to compounds containing forerunner simple works till cycloalkane very recent rings, mainly cyclohexane or cyclobutane derivatives. Cholesterol-based organogelators results that deal with the gelling ability and self-assembling of carbocycle-based organogela- are also tors discussed is afforded. Thebecause role of of thetheir versatility chirality allowing toand in the monomers design and in the prepare tailor-made aggregates is em- phasized. Specialwith organogelators attention has been interesting paid to compounds containing simple cycloalkane properties. rings, mainly cyclohexane or cyclobutane derivatives. Cholesterol-based organogelators are also discussedDerivatives 2. Cyclohexane because of their versatility allowing to design and prepare tailor-made organogelators with interesting properties. In this section, the gelling abilities of bisamide and bisurea derivatives are extensively commented 2. Cyclohexane because they have been used by several authors to shed light on the role of Derivatives balanced In thishydrogen section, thebonding and van gelling abilities of der Waalsand bisamide interactions as the driving bisurea derivatives force to pro- are extensively commented because they have been used by several authors to shed light on the role of and duce gels. Attention is paid to the relationship between the chirality of the monomers that of the balanced aggregates. hydrogen bondingTheand influence van der of the interactions Waals substituents, placed as the on force driving the cyclohexane to produce ring and of gels. the side-chain Attention is paid tolength is also considered. the relationship between the chirality of the monomers and that of the aggregates. The influence of the substituents, placed on the cyclohexane ring and of the 2.1.side-chain length is Dialkyl Bisamide andalso considered. Organogelators Bisurea-Based The simplest 2.1. Dialkyl Bisamidegelators are derivatives and Bisurea-Based of trans-1,2-diaminocyclohexane or trans-cyclo- Organogelators hexane-1,2-dicarboxylic acid. Both present a C2 axis of symmetry and are commercial The simplest gelators are derivatives of trans-1,2-diaminocyclohexane or trans-cyclohexane- products available 1,2-dicarboxylic acid.inBoth the two enantiomerically present pure forms. a C2 axis of symmetry and are commercial products In a pioneer work, Hanabusa et al. available in the two enantiomerically pure forms. described the synthesis and study of LMWOGs 1– 3 (Figure 1) [27].work, In a pioneer Compound Hanabusa 1 was et al.prepared describedby thethe reaction synthesis andofstudy (1R,2R)-1,2-diaminocy- of LMWOGs clohexane 1–3 (Figure and lauroyl 1) [27]. chloride Compound in the 1 was presence prepared by of thetriethylamine. Derivatives 2 and 3 were reaction of (1R,2R)-1,2-diaminocy- prepared in clohexane anda similar way. Compound lauroyl chloride 1 wasofable in the presence to gelate a Derivatives triethylamine. variety of solvents of diverse 2 and 3 were prepared in a similar polarity and way. Compound functionality, 1 wasmethanol, such hexane, able to gelate a variety ethyl ofacetone, acetate, solvents of diverse acetonitrile, di- polarity and functionality, such hexane, methanol, ethyl acetate, acetone, oxane, toluene and N,N-dimethylformamide, affording gels that were stable at 25 °C for acetonitrile, dioxane, six months.toluene and N,N-dimethylformamide, A similar behavior was observed for affording gels that were the enantiomer stable at 25 ◦the 2. Interestingly, C race- for six months. A similar behavior was observed for the enantiomer 2. Interestingly, mate only formed unstable gels that were converted to cocrystals after several hours. In the racemate only formed unstable gels that were converted to cocrystals after several hours. turn, the achiral cis-derivative 3, prepared from cis-cyclohexane-1,2-dicarboxylic acid, In turn, the achiral cis-derivative 3, prepared from cis-cyclohexane-1,2-dicarboxylic acid, formed no gels with any of the liquids tested. Gelation was dependent of the length of the formed no gels with any of the liquids tested. Gelation was dependent of the length of the hydrophobicside hydrophobic sidechain chaininin1 since 1 since gels gels failfail to form to form whenwhen the alkyl the alkyl tail shortened tail was was shortened to to four carbons. four carbons. Figure1.1.Cyclohexane-containing Figure Cyclohexane-containing bisamides based bisamides on cyclohexane-1,2-diamine. based on cyclohexane-1,2-diamine. Gels from acetonitrile were investigated by Transmission Electron Microscopy (TEM) Gels from acetonitrile were investigated by Transmission Electron Microscopy (TEM) revealing nano-sized helical fibers. The helicity was right-handed for (R,R)-1 and left- revealing nano-sized helical fibers. The helicity was right-handed for (R,R)-1 and left- handed for its enantiomer, (S,S)-2. As a result of Molecular Modeling (MD) studies, handed for its enantiomer, (S,S)-2. As a result of Molecular Modeling (MD) studies, au- authors suggested that such structures are induced by the formation of two intermolecular thors suggested hydrogen that such bonds between structures each molecule.are induced Thus, by the formation the two-equatorial of twoand amide-NH intermolecular amide- hydrogen CO bonds could direct between each themselves molecule. antiparallel Thus, to each theand other two-equatorial perpendicularamide-NH and amide- to the cyclohexyl CO could direct themselves antiparallel to each other and perpendicular to ring promoting the formation of an extended molecular tape (Figure 2). Although hydrogen the cyclohexyl ring promoting bonding betweenthe formation amide groups inofconsecutive an extended molecular molecules hastape also (Figure 2). Although been proposed by otherhydro- authors in laterbetween gen bonding studies to explain amide the self-assembling groups in consecutive mode of related molecules systems has (see below), also been proposed by such otheraauthors cyclohexane stacking in later has to studies notexplain been supported neither by experimental the self-assembling evidence mode of related nor (see systems by recent computational studies. Gels 2021, 7, x FOR PEER REVIEW 3 of 25 Gels 2021, 7, x FOR PEER REVIEW 3 of 25 Gels 2021, 7, 54 below), such a cyclohexane stacking has not been supported neither by experimental 3 of 24 evi- below), such a cyclohexane stacking has not been supported neither by experimental evi- dence nor by recent computational studies. dence nor by recent computational studies. Figure 2. Suggested model to explain the helicoidal aggregates from 1. Adapted with permission Figure Figure 2. Suggested from modeltotoexplain Suggested model Wiley [27]. explainthe the helicoidal helicoidal aggregates aggregates from from 1. Adapted 1. Adapted withwith permission permission from from Wiley [27]. Wiley [27]. Later, Later,amphiphilic amphiphilic cationic compounds 44and andtheir theirenantiomers enantiomers were investigated. Later, amphiphiliccationic cationic compounds compounds 4 and their were enantiomers investigated. were investigated. They formed self-assembled rods in ethanol as verified by Scanning Electron Microscopy They formed self-assembled rods in ethanol as verified by Scanning Electron Microscopy They formed self-assembled rods in ethanol as verified by Scanning Electron Microscopy (SEM) and (SEM) andTEM TEM(Figure (Figure 3a) 3a) [28]. (SEM) and TEM (Figure 3a) [28]. Figure 3. Structure Figure of amphiphilic 3. Structure of amphiphilicorganogelators 4aand organogelators 4a and4b4b and and SEMSEM images images of (a)of (a) self-assembled self-assembled 3a in ethanol; 3a in ethanol; (b) tan- (b) tantalum Figure talum 3. Structure oxide of amphiphilic right-handed fibers organogelators obtained 4a and 4b and SEM images of ACS (a) self-assembled 3a in ethanol; (b) tan- oxide right-handed fibers obtained from from 4b. Adapted 4b. Adapted with permission with permission from ACS from[28,29]. [28,29]. talum oxide right-handed fibers obtained from 4b. Adapted with permission from ACS [28,29]. These These super-structures were super-structures were used usedas astemplates templatesfor the for thepreparation preparationof tubular helical of tubular helical fiber These super-structures materials of transition were metal (Ti, used Ta, V) as templates oxides. The for the helices of preparation metal oxides of tubular were always helical fiber materials of transition metal (Ti, Ta, V) oxides. The helices of metal oxides were al- fiber materials left-handed in theof sol-gel transition systemmetal of the(Ti, Ta, V) oxides. The (R,R)-enantiomer, helices3b) 4b (Figure ofand metal oxides were al- right-handed ways left-handed in the sol-gel system of the (R,R)-enantiomer, 4b (Figure 3b) and right- ways in the left-handed in the sol-gel system case of the (S,S)-enantiomer [29]. of the (R,R)-enantiomer, 4b (Figure 3b) and right- handed in the case of the (S,S)-enantiomer [29]. handed Theinpreparation the case of of thehelically structured [29]. (S,S)-enantiomer silica by a sol-gel transcription in chiral The preparation of helically structured silica by a sol-gel transcription in chiral or- organogel systems including The preparation bisamide of helically and bisurea structured derivatives silica wastranscription by a sol-gel reported by Shinkai in chiral or- ganogel et al. systems [30,31]. including Figure 4 shows bisamide the and bisurea of (R,R)-enantiomers derivatives cationic was reported amphiphile 5 and by Shinkai bisurea 6. et et ganogel systems including bisamide and bisurea derivatives was reported by Shinkai al. Bisamides [30,31]. Figure 4 shows and 2 (Figure the (R,R)-enantiomers 1) the were(R,R)-enantiomers also used as gelatorsof cationic amphiphile 5 and bisurea 6. al. [30,31]. 1Figure 4 shows ofincationic that work. amphiphile 5 and bisurea 6. Bisamides 1 andgelators Cationic 2 (Figure 1) 7were 5 and werealso worseused thanasrelated gelators in that work. bisamides and bisureas since they Bisamides 1 and 2 (Figure 1) were also used as gelators in that work. were soluble in protic solvents like alcohols and acetic acid or strongly polar aprotic dimethylsulfoxide (DMSO). They gelated aprotic acetone, acetonitrile, tetrahydrofuran (THF), DMF or cyclohexane but were insoluble in n-hexane. In turn, bisureas 6 and 8 behaved similarly to bisamides 1 and 2. However, they were insoluble in acetone and acetonitrile. (R) NH-C-C10H 20N(CH3 )3 Br (R) NH-C-NHC 11 H23 O O 5 6 GelsGels 2021, 7, x7,FOR 2021, 54 PEER REVIEW 4 of 24 4 O O (S) (S) NH-C-C10H20N(CH3)3 Br NH-C-NHC 11 H23 O O (S) NH-C-C 10H 20 N(CH 3)3 (R) Br NH-C-NHC 11 H23 (S) (R) NH-C-C H N(CH ) Br NH-C-NHC 11 H23 O 10 20 3 3 O 7 8 (R) NH-C-C 10 H 20N(CH 3 )3 Br (R) NH-C-NHC 11 H23 O Figure 4. Enantiomeric O cationic gelators 5 and 7 and urea-based neutral gelators 6 and 8. 5 6 Cationic gelators 5 and 7 were worse than related bisamides and bisureas sin O O were (S) soluble in protic solvents like alcohols (S) and acetic acid or strongly polar apr NH-C-C H20N(CH3)3 Br NH-C-NHC 11 H23 methylsulfoxide10 (DMSO). They gelated aprotic acetone, acetonitrile, tetrahydr (THF), DMF or cyclohexane but were insoluble in n-hexane. In turn, bisureas 6 an (S) NH-C-C H N(CH 3)3 Br (S) NH-C-NHC 11 H23 haved similarly10to 20 bisamides 1 and 2. However, they were insoluble in acetone an O O tonitrile. 7 8 Since the presence of the cationic charge in the organogel fibers was as an ind Enantiomeric cationic gelators 5 and 75and andurea-based neutral gelators Figure Figure sable 4.4. featureEnantiomeric to efficient cationic sol-gelgelators 7 andmixtures transcription, urea-based 1 + 65,and ofneutral +8.6, 2 6+ and 5gelators 8. 7 + 7 and applied Since asthegelators presence in order of the to maintain cationic charge in thethe high gelation organogel fibers was ability and moderate c as an indispensable charge Cationic feature to density. gelators 5 SEM pictures efficient sol-gel and 7 were worse of mixtures transcription, xerogelsofofthan related 1 +these bisamides 5, 5 + 6,mixtures 2 + 7 and 7(1:1 and wt %) + 8 were bisureas from since applied aceto were as soluble gelators in in order protic to solvents maintain the like high alcohols gelation and ability acetic and showed nanosized helical fibers for the aggregates. The helicity was left-handed acid moderateor strongly cationic polar charge aproti methylsulfoxide (DMSO). They gelated aprotic (1:1 wtacetone, for 2acetonitrile, tetrahydrof density. SEM pictures of xerogels of these mixtures %) from acetonitrile showed mixture 1 + 5 (R enantiomer) and always right-handed + 7 (S enantiomer). Co nanosized helical fibers for the aggregates. The helicity was left-handed (THF), DMF or cyclohexane but were insoluble in n-hexane. In turn, bisureas 6 and for the mixture wise, + 5 (Rforenantiomer) xerogel samples ofright-handed 2 + 5 (1:1 wt for %) 2 + 7obtained fromContrariwise, ethanol, helicity was 1haved similarly toand always bisamides 1 and 2. However, (Sthey enantiomer). were insoluble for in acetone and handed for the of xerogel samples R 2enantiomers and left-handed + 5 (1:1 wt %) obtained from ethanol,forhelicity the S enantiomers. was right-handed These for result tonitrile. R enantiomers S enantiomers. intheagreement with andthe left-handed sign of forthethe Cotton These results effect observed in were in agreement the Circular Dichroism with theSince signthe presence of the of the Cotton effect cationic observed in charge in the the Circular organogel Dichroism (CD)fibers spectrawas as an indis of these spectra of these xerogels (Figure 5). sable feature xerogels (Figureto 5).efficient sol-gel transcription, mixtures of 1 + 5, 5 + 6, 2 + 7 and 7 + 8 applied as gelators in order to maintain the high gelation ability and moderate cat charge density. SEM pictures of xerogels of these mixtures (1:1 wt %) from aceton showed nanosized helical fibers for the aggregates. The helicity was left-handed fo mixture 1 + 5 (R enantiomer) and always right-handed for 2 + 7 (S enantiomer). Con wise, for xerogel samples of 2 + 5 (1:1 wt %) obtained from ethanol, helicity was r handed for the R enantiomers and left-handed for the S enantiomers. These results in agreement with the sign of the Cotton effect observed in the Circular Dichroism spectra of these xerogels (Figure 5). 5. CD Figure 5. Figure CDspectra spectraof 1of+15 + (1:1 wt %) 5 (1:1 wtand + 7 (1:1 %)2 and 2 +wt7 %) (1:1organogels obtained from wt %) organogels acetonitrile: obtained from aceto ◦ − 3 − 1 25 C, total gelator concentration: 4.18 × 10 mol−3L . Adapted with permission from Wiley [31]. 25 °C, total gelator concentration: 4.18 × 10 mol L . Adapted with permission from Wiley −1 The transcription of the chiral, helical structures of the organogels into silica gel was The transcription achieved of the chiral, by sol-gel polycondensation of helical structures tetraethoxysilane of theInorganogels (TEOS). all cases, theinto left- silica g achieved by sol-gel polycondensation of tetraethoxysilane (TEOS). In allorcases, th and right-handed structures of the silica could be created by transcription of the left- right-handed and structures right-handed of the organogel structures of the systems. silica could be created by transcription of the Some years later, van Esch et al., investigated on the balanced influence of hydrogen right-handed structures of the organogel systems. bonding and van der Waals interactions on the gelation of cyclohexane-based bisamide and bisurea derivatives later, Some years vanprepared [32]. They Esch etcompounds al., investigated 9 and 10on the balanced bearing alkyl tails ofinfluence different of hyd Figure (Figure bonding lengths 5.and CD spectra van 6) and of der 1Waals their+gelation 5 (1:1interactions wtbehavior %) and with 2 +on 7 different (1:1 thewtgelation %) organogels solventsof was obtained from acetonit cyclohexane-based explored. bis 25 °C, total gelator concentration: 4.18 × 10−3 mol L−1. Adapted with permission from Wiley [31 and bisurea derivatives [32]. They prepared compounds 9 and 10 bearing alkyl different lengths (Figure 6) and their gelation behavior with different solvents w The transcription of the chiral, helical structures of the organogels into silica gel plored. achieved by sol-gel polycondensation of tetraethoxysilane (TEOS). In all cases, the and right-handed structures of the silica could be created by transcription of the le right-handed structures of the organogel systems. Some years later, van Esch et al., investigated on the balanced influence of hydr bonding and van der Waals interactions on the gelation of cyclohexane-based bisa Gels 2021, 7, x 7,FOR Gels 2021, 54 PEER REVIEW 5 of 24 Figure 6. Cyclohexane-based bisamide and bisurea organogelators bearing alkyl chains of ent lengths. For the bisamide with a C2-alkyl tail, the formation of intermolecular hydroge and interactions of the cyclohexyl rings were expected to be the major driving f Figure6. 6. gelation, Figure Cyclohexane-based because the van Cyclohexane-based derbisamide bisamide Waals and bisurea organogelators interactions and bisurea cannot organogelators alkylbearing contribute bearing inofalkyl chains adiffer-chains of significant ent ent lengths. lengths. Indeed, gelation was not observed in protic solvents capable to interfere with hy bondingFor thebut it gelated bisamide with aapolar C2 -alkylsolvents and wasofsoluble tail, the formation in alcohols intermolecular hydrogenandbonds DMSO. In c compounds and For the interactionswithbisamide with of theCcyclohexyl 5–C13 alkyl a C 2-alkyl tail, the formation of intermolecular hydroge tailswere rings formed expected gelstowith be theeither apolar force major driving or polar for solve can not interfere with hydrogen bonding, i.e., ethyl acetate. With C15– anddriving and interactions gelation, because the of van the der cyclohexyl Waals rings interactions were cannot expected contribute in to a be the significantmajor manner. C17– bis gelation, Indeed, because gelation was the van not observedder Waals in proticinteractions solvents capable gelation also occurred in protic polar solvents, such as isopropanol, in addition, tcannot contribute to interfere in a with hydrogen significant bonding Indeed, but it gelatedwas gelation apolarnotsolvents observed and wasin soluble solvents protic in alcoholscapable and DMSO. to In contrast, with h interfere compounds with C5 –C13 alkyl tails formed gels with either apolar or polar solvents that (cgc) w polar and apolar solvents tested. Their critical gelation concentration bonding enough but itwt (<0.5 gelated with%) apolar to classify solvents them and i.e.,asethyl was soluble in–conclusion, supergelators. acetate. With CIn alcohols and theDMSO. elongatioIn can not interfere hydrogen bonding, 15 and C17 – bisamides, compounds gelation alkyl tail with Cin5–C alsoinoccurred bisamide 13 alkyl protic polar tails organogelators formed solvents, ledsuch toas gels withcgc,either isopropanol, lower apolar in addition, mainly toor in polar allpolar the solve solvents, can not polar this and interfere effectapolar solvents was less with hydrogen tested. pronounced bonding, Their critical in apolar i.e.,concentration gelation ethyl acetate. solvents. (cgc)With was lowC15enough – and C17– bis (<0.5 wt gelation %) to classify also occurred them as supergelators. in protic polar In conclusion, solvents, the elongation of the alkyl tail Bisurea-based in bisamide organogelators gelators led to were lower cgc,lessmainly soluble insuch in polarapolar as isopropanol, solvents,solvents whereasthan inbisamides. addition, this effect t polar ing andtail of the apolar length solvents allowed tested. the formationTheir criticalof gels gelation either in concentration apolar and polar (cgc) solvw was less pronounced in apolar solvents. enough n = 10–18. (<0.5 wt C16–tail Bisurea-based %) to bisurea gelators classify were seemed them less soluble as to have supergelators. the solvents in apolar optimalthan In conclusion, length and showed bisamides. the elongatio Increas- the lo alkyl ing of tail the in tail bisamide length allowedorganogelators the values being also classified as supergelator. formation led of to gels lower either in cgc, mainly apolar and in polar polar solvents, solvents this for n =effect 10–18.was As abeing lessconclusion C16 –tail general pronounced bisurea seemed to inhave of this apolar work,solvents. the optimal length and showed the lowest it was demonstrated that for these orga cgc values Bisurea-based also classified gelators as supergelator. were less soluble in role apolar solvents than whereas bisamides. tors,Asvan der Waals a general conclusioninteractions of this work, play it wasa dominant demonstrated thatinfor polar thesesolvents organogelators, hy ing bonding van of the der Waals tail length interactions interactions allowed dominate the play a dominant formation in apolar roleones. of in polar gels These either results solvents in apolar and pointhydrogen- whereas polar out the signific solv n = bonding10–18. C 16–taildominate interactions bisurea seemed in apolar of solvent in driving the assembly of the gel fibers. to ones. have These the optimal results point length out the and showed significant role the lo values of solvent The being in also classified driving regioisomeric the assembly as supergelator.bisamides 11 and 12 (Figure 7), that is of the cyclohexane-based gel fibers. The As regioisomeric a general cyclohexane-based conclusion of thisbisamides work,acid, 11 and it was 12 (Figure 7), that demonstrated is, deriva- that for these tivesofof tives thethe cyclohexane-1,2-dicarboxylic cyclohexane-1,2-dicarboxylic acid, related to 1,related to 1,also 3 and 9, have 3 and been9, have examined also org bee tors, ined van der as LMWOGs Waals interactions [33]. play a dominant role in polar solvents whereas hy as LMWOGs [33]. bonding interactions dominate in apolar ones. These results point out the signifi of solvent O in driving the assembly of O the gel fibers. The (R) regioisomeric C-NH-(CH 2)15CH3 cyclohexane-based (R) C-NH-(CH bisamides 2)15CH3 11 and 12 (Figure 7), that is tives of the cyclohexane-1,2-dicarboxylic acid, related to 1, 3 and 9, have also bee ined(R)asC-NH-(CH LMWOGs) [33]. CH (S) C-NH-(CH ) CH 2 15 3 2 15 3 O O O O 11 (R) C-NH-(CH ) CH (R) 12 2 15 3 C-NH-(CH2)15CH3 Figure Cyclohexane-containing Figure7. 7. bisamides Cyclohexane-containing based on based bisamides cyclohexane-1,2-dicarboxylic acid. on cyclohexane-1,2-dicarboxylic acid. (R) C-NH-(CH2)15CH3 compounds were synthesized byC-NH-(CH 2)15CH3 peptide coupling protocols. (S) These means of standard These Both were compounds Oinsoluble were in solvents synthesized with byconstants highOdielectric means of (ε) standard but chiralitypeptide played acouplin cols. Bothrole significant were insoluble 11in the ability toingelate solvents with solvents high 12with ε