Giant oligomeric porous cage-based molecules

Giant oligomeric porous cage-based molecules† Alba Cort´ es-Mart´ ınez, ab Cornelia von Baeckmann, ab Laura Hern´ andez-L´ opez, ab Arnau Carn´ e-S´ anchez * ab and Daniel Maspoch * abc Most reported porous materials are either extended networks or monomeric discrete cavities; indeed, porous structures of intermediate size have scarcely been explored. Herein, we present the stepwise linkage of discrete porous metal–organic cages or polyhedra (MOPs) into oligomeric structures with afinite number of MOP units. The synthesis of these new oligomeric porous molecules entails the preparation of 1-connected (1-c) MOPs with only one available azide reactive site on their surface. The azide-terminated 1-c MOP is linked through copper(I)-catalysed azide–alkyne cycloaddition click chemistry with additional alkyne-terminated 1-c MOPs, 4-c clusters, or 24-c MOPs to yield three classes of giant oligomeric molecules: dimeric, tetrameric, or satellite-like, respectively. Importantly, all the giant molecules that we synthesised are soluble in water and permanently porous in the solid state. Introduction The overwhelming majority of known porous materials are either small (<5 nm) discrete cages (i.e. coordination and covalent cages), 1–5 or innite networks (i.e. metaland covalentorganic frameworks). 6–9 The chemical and dimensional (between 5 nm and 20 nm) space between these two classes has not been largely explored, due to the inherent synthetic and analytical challenges (Scheme 1). 10–12 Specically, using bottomup approaches to assemble large porous discrete cages is not trivial. 13 Another challenge lies in stopping the polymerisation reaction of extended networks at the oligomeric regime, which is not thermodynamically favoured, thus leading to polydisperse and metastable materials. 14,15 Moreover, the downsizing of crystalline porous networks below the 20 nm threshold oen entails the accumulation of defects that are detrimental to their characterisation and function. 16,17 To overcome these challenges, one can take inspiration from the stepwise synthesis of giant organic 18–22 and metal– organic 23–25 molecules, in which each growing step proceeds through thermodynamic control. In the case of porous materials, this strategy entails the oligomerization of single pore units into giant multi-pore molecules. Pioneer studies have shown the viability of the pore oligomerization approach by either interlocking 26–29 or linking a dened number of cages 30–32 Scheme 1 Illustrated scale of the regimes of reported porous materials. a Catalan Institute of Nanoscience and Nanotechnology (ICN2), CSIC and The Barcelona Institute of Science and Technology, Campus UAB, Bellaterra, 08193 Barcelona, Spain. E-mail: [email protected]; daniel.maspo[email protected] b Departament de Qu´ ımica, Facultat de Ci` encies, Universitat Aut` onoma de Barcelona (UAB), Cerdanyola del Vall` es, 08193 Barcelona, Spain c ICREA, Pg. Llu´ ıs Companys 23, 08010 Barcelona, Spain †Electronic supplementary information (ESI) available. See DOI: https://doi.org/10.1039/d4sc01974a Cite this: Chem. Sci.,2024,15, 7992 All publication charges for this article have been paid for by the Royal Society of Chemistry Received 25th March 2024 Accepted 29th April 2024 DOI: 10.1039/d4sc01974a rsc.li/chemical-science 7992 |Chem. Sci.,2024,15, 7992–7998 © 2024 The Author(s). Published by the Royal Society of Chemistry Chemical Science EDGE ARTICLE Open Access Article. Published on 30 April 2024. Downloaded on 1/3/2025 1:42:55 PM. This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. View Article Online View Journal | View Issue into multi-cage molecules. However, to the best of our knowledge, the permanent porosity of this giant molecules has not yet been demonstrated. Herein we report the stepwise synthesis of permanently porous oligomeric molecules by the concatenation of a dened, nite number of metal–organic cages or polyhedra (MOPs). The resultant giant oligomeric porous molecules merge the properties that arise from linking pore-units (i.e. extrinsic porosity and inter-cavity cooperativity) 33,34 to the those typically observed in molecules, such as dened molecular weight, stoichiometric reactivity, and solubility in liquids, including water. 21–23,35 In our synthetic route to oligomeric porous molecules, the building blocks are robust Rh(II)-based MOPs (Rh-MOPs). 36 RhMOPs can have up to 24 covalent reactive sites on their external surfaces, stemming from the 5-position of the 1,3-benzendicarboxylate (BDC) derivative used in their synthesis. 37 Consequently, the high connectivity of Rh-MOPs complicates the control of their polymerisation into well-dened oligomeric structures rather than extended networks. 38–41 To address this challenge, we aimed to create Rh-MOPs with only one reactive site on their surface. By employing protecting groups, we selectively masked the reactivity of 23 of the 24 reactive sites to yield 1connected (1-c) Rh-MOPs. 42 Next, using orthogonal chemistry, we assembled these 1-c MOPs with other 1-c MOPs or with 4-c clusters or 24-c Rh-MOPs to yield giant oligomeric molecules of three types: dimeric, tetrameric, or satellite-like (Fig. 1). Results and discussion Synthesis of 1-connected Rh-MOPs We began the synthesis of 1-c Rh-MOP from a Rh-MOP in which all of its 24 peripheral carboxylic acid groups were protected with 2-(trimethylsilyl)ethyl (TSE) groups. One of the 24 TSE groups was selectively cleaved by treating the fully protected RhMOP with 1.5 mol eq. (per MOP) of the deprotecting agent tetrabutylammonium uoride (TBAF). This reaction afforded a new Rh-MOP having only one available surface carboxylic group with the formula (COOTSE-BDC) 23 (BTC) 1 Rh 24 (where BTC =1,3,5-benzenetricarboxylate; and COOTSE-BDC 24 =5-((2- (trimethylsilyl)ethoxy)carbonyl)-1,3-benzendicarboxylate). The integrity and formula of the 1-c Rh-MOP (hereaer, (COOH) 1 - RhMOP) was conrmed by Matrix-Assisted Laser Desorption/ Ionisation-Time-Of-Flight (MALDI-TOF) mass spectroscopy, which showed a peak centered at 9770 m/zthat corresponds to the expected molecular formula of [(COOTSE-BDC) 23 (BTC) 1 Rh 24 +H + ] + $2H 2 O (expected mass of 9776 g mol −1 ) (Fig. 2a and S4†). Analysis of the 1 H-NMR spectrum of the acid digested (COOH) 1 - RhMOP conrmed the expected ratio between the aromatic and the aliphatic protons of the protected ligand, thus conrming the removal of one protecting group (Fig. S3†). Furthermore, Diffusion-Ordered Spectroscopy (DOSY) NMR analysis of the (COOH) 1 -RhMOP in CDCl 3 revealed the same diffusion coefficient of 1.9 ×10 −10 m 2 s −1 for both aliphatic and aromatic Fig. 1 (Top) Schematic of the synthesis of 1-c MOPs terminated with azide or alkyne groups, and their subsequent linkage to other MOPs or clusters through click chemistry to form oligomeric porous dimeric, tetrameric or satellite-like molecules. (Bottom) Representative reaction schematic for the synthesis of giant, oligomeric, MOP-based molecules. © 2024 The Author(s). Published by the Royal Society of Chemistry Chem. Sci.,2024,15, 7992–7998 | 7993 Edge Article Chemical Science Open Access Article. Published on 30 April 2024. Downloaded on 1/3/2025 1:42:55 PM. This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. View Article Online signals, which further corroborated that the product had retained 23 of its original 24 TSE groups (Fig. S2†). Next, to confer (COOH) 1 -RhMOP with the orthogonal reactivity required to oligomerise it with additional MOPs, we functionalised its surface with a single polyethylene glycol (PEG) chain terminated with either alkyne or azide group. Thus, (COOH) 1 -RhMOP was reacted with a PEG chain terminated at one end with a primary amine (for coupling to the surface carboxylic acid), and at the other end, with either an alkyne or azide moiety (for the oligomerisation). The coupling reactions between (COOH) 1 -RhMOP and either NH 2 -PEG 38 -N 3 or NH 2 - PEG 38 -alkyne proceeded homogenously in N,N-dimethylformamide (DMF), using 1-hydroxybenzotriazole (HOBt), 2-(1Hbenzotriazole-1-yl)-1,1,3,3-tetramethyluronium hexa- uorophosphate (HBTU), and N,N-diisopropylethylamine (DIPEA) as coupling agents. They yielded two distinct MOPs, each with only one PEG chain attached at its surface: an azideterminated one, having the formula (COOTSE-BDC) 23 (N 3 -PEG 38 - BDC)Rh 24 (hereaer, (N 3 ) 1 -RhMOP); and an alkyne-terminated one, having the formula (COOTSE-BDC) 23 (alkyne-PEG 38 -BDC) Rh 24 (hereaer, (alkyne) 1 -RhMOP). The coupling of a single functionalised PEG chain on the surface of (COOH) 1 -RhMOP was rst demonstrated by MALDI-TOF mass spectroscopy, which showed the expected mass for each product: 11 540 m/z for (N 3 ) 1 -RhMOP and 11 521 m/zfor (alkyne) 1 -RhMOP (Fig. 2a, S10 and S16†respectively). Both values agree with the respective calculated molecular weights for the corresponding expected molecular formulae of the 1-c Rh-MOPs: 11 544 ±480 g mol −1 for [(COOTSE-BDC) 23 (N 3 -PEG 38 -BDC)Rh 24 +H + ] + and 11 521 ± 370 g mol −1 for [(COOTSE-BDC) 23 (N 3 -PEG 38 -BDC)Rh 24 +H + ] + . The formation of a single amide bond on the surface of the MOP was further supported by the 1 H-NMR analysis of the corresponding acid-digested samples: the spectra revealed the quantitative transformation of the initial BTC linker into a PEG functionalised BDC linker via amide-bond formation (Fig. S9 and S15†). The ratio between the PEG-functionalised BDC and COOTSE-BDC was found to be the expected value of 1 : 23 in both (N 3 ) 1 -RhMOP and (alkyne) 1 -RhMOP (Fig. S7 and S13†). The DOSY analysis of (N 3 ) 1 -RhMOP and (alkyne) 1 -RhMOP revealed a single diffusion-coefficient for the MOP core and the PEG chain in both products: 1.8 ×10 −10 m 2 s −1 and 1.7 ×10 −10 m 2 s −1 respectively (Fig. S8 and S14†). Interestingly, the remaining 23 protected carboxylic acid groups on the surface of (N 3 ) 1 - RhMOP and (alkyne) 1 -RhMOP could be removed by treating both 1-c RhMOPs with excess of TBAF. Under these conditions, both deprotected (N 3 ) 1 -RhMOP and (alkyne) 1 -RhMOP were functionalized with 23 carboxylic acid groups (Fig. S19–S30†). Finally, to corroborate the synthesis of pure (COOH) 1 - RhMOP and derived mono-PEGylated compounds, we performed a control experiment consisting of reacting (COOH) 1 - RhMOP (obtained by treating a TSE-protected Rh-MOP with 1.5 mol eq. of TBAF) with an excess amount of NH 2 -PEG 38 -N 3 (5 mol eq. per Rh-MOP). The product obtained from this reaction was analysed through MALDI-TOF mass spectrometry, showing only the peak corresponding to (N 3 ) 1 -RhMOP that contains one attached PEG chain on the MOP surface (Fig. S31†). Conversely, when NH 2 -PEG 38 -N 3 was reacted with Rh-MOPs containing a higher percentage of free carboxylic acid groups on their surface, a distribution of multi-PEGylated RhMOPs was obtained as a product. Specically, PEGylated RhMOPs with 2 and 3 PEG chains on their surface were obtained when 5 mol eq. of NH 2 -PEG 38 -N 3 was reacted with TSE-protected Rh-MOPs treated with 3 and 5 mol eq. of TBAF, respectively (Fig. S32†). These experiments conrm the successful synthesis of pure (COOH) 1 -RhMOP as the presence of Rh-MOPs with a higher number of available carboxylic acids on their surface would yield a distribution of PEGylated Rh-MOPs in the presence of excess of NH 2 -PEG 38 -N 3 . Synthesis of the oligomeric dimeric MOP-based molecule Next, we synthesised a dimeric MOP-based molecule (hereaer, MOP-dimer), by coupling (N 3 ) 1 -RhMOP to (alkyne) 1 -RhMOP through a copper(I)-catalysed, azide–alkyne cycloaddition Fig. 2 (a) Comparison of the MALDI-TOF spectra of (COOH) 1 -RhMOP (blue), (N 3 ) 1 -RhMOP (green) and (alkyne) 1 -RhMOP (red) which evidences an increase in mass due to the attachment of a chain of NH 2 PEG 38 X to the MOP (where X =N 3 or alkyne). (b) MALDI-TOF spectrum of the MOP-dimer, showing the single broad peak centered at 18 538 m/z. (c) DOSY-NMR spectrum of the MOP-dimer. (d) 1 HNMR spectrum of the acid-digested MOP-dimer. 7994 |Chem. Sci.,2024,15, 7992–7998 © 2024 The Author(s). Published by the Royal Society of Chemistry Chemical Science Edge Article Open Access Article. Published on 30 April 2024. Downloaded on 1/3/2025 1:42:55 PM. This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. View Article Online (CuAAC) click reaction. 43 To this end, both MOPs were reacted under homogenous conditions in a mixture of CH 2 Cl 2 /DMF (1 : 1), using copper sulphate and sodium acetate as catalysts, to afford the corresponding crude products as a green solid. To facilitate the purication of the MOP-dimer, all surface TSE protecting groups were cleaved, which yielded a dimeric MOP in which each MOP unit had 23 available carboxylic acid groups. Next, the MOP-dimer was puried through successive washing with 0.3 M HCl and basic MeOH, in which the dimer is insoluble, but the catalyst and unreacted precursors are soluble. The obtained puried product exhibited pH-dependent aqueous solubility, which we ascribed to the presence of up to 46 available carboxylic groups. Once deprotonated, the carboxylate groups imparted negative charge to the resulting MOP-dimer, as conrmed by Z-potential measurements performed in basic water, which revealed a value of –48.5 ±6.9 mV for the MOPdimer (Fig. S41†). The successful dimerization of two different MOPs was rst evidenced by MALDI-TOF. The spectrum exhibited a single broad peak centred at 18 538 m/z,ingoodagreement with the expected mass (18 539 ±850 g mol −1 ) for the MOPdimer having a molecular formula of [(COOH-BDC) 46 (BDCPEG 38 -1H-1,2,3-triazol-4-yl-PEG 38 -BDC) 1 Rh 48 -H + ] − $DMF (Fig. 2b and S38†). DOSY NMR spectroscopy in basic D 2 Orevealed adecreaseinthediffusion coefficient from the deprotected 1-c MOP precursors (6.6 ×10 −10 m 2 s −1 and 6.9 ×10 −10 m 2 s −1 )to the MOP-dimer (6.2 ×10 −10 m 2 s −1 ) (Fig. 2c, S20, S26 and S34†). 44 Analogously, Dynamic Light Scattering (DLS) measurements revealed that the molecule size in solution had increased from that of the deprotected (N 3 ) 1 -RhMOP (2.6 ±0.2 nm) or the deprotected (alkyne) 1 -RhMOP (2.3 ±0.3 nm), to that of the MOPdimer (6.3 ±1.1 nm) (Fig. 3a, S24, S30 and S40†). To conrm that the two MOPs in MOP-dimer were linked through a covalent bond (i.e. the triazole ring formed upon the CuAAC reaction) and not simply entangled through supramolecular PEG-MOP interactions, we submitted it to acid digestion and then, analysed the resultant ligands through 1 H-NMR (Fig. 2d). The spectrum of the isolated PEG linker clearly showed a peak at 8.11 ppm, which can be ascribed to the proton of the expected triazole ring (Fig. S35–S37†). Further analysis of the relative integration of the triazole ring and the aromatic core belonging to the Rh-MOP conrmed that every 1-c Rh-MOP was linked through a triazole ring. Together, these data conrmed that the two MOPs had indeed been assembled into one new dimer, thus corroborating our original idea that this could be accomplished by strategically controlling the number of reactive sites on the surface of the MOP precursors, and then subjecting them to orthogonal click chemistry. Increasing the connectivity in the synthesis of oligomeric MOP-based molecules: a MOP-tetramer and a MOP-satellite Having conrmed the viability of the MOP oligomerisation, we next targeted oligomeric structures having a higher number of MOP units. We began by synthesising a tetrameric structure in which four 1-c MOPs are linked to a single 4-c node that comprises a dirhodium paddlewheel unit (Fig. 1). The starting point was the Rh 2 (bdc) 4 cluster, which has four available carboxylic acid groups, 45 which were used to attach, via amide coupling, four alkyne-terminated NH 2 -PEG 6 -alkyne chains (Fig. S42–S45†). Next, (N 3 ) 1 -RhMOP (10 mol eq.) was reacted with the synthesised alkyne-functionalised 4-c cluster in a mixture of CH 2 Cl 2 /DMF (1 : 1), using copper sulfate and sodium ascorbate as CuAAC catalysts. The reaction proceeded homogenously and, aer 48 hours, it was quenched by extracting the crude reaction with 0.3 M HCl and water to remove the catalysts. The remaining organic solvent was removed in vacuo, and the resultant crude product was treated with TBAF to deprotect all the carboxylic acid groups present in the mixture. To purify the carboxylic acid-functionalised tetramer (hereaer, MOP-tetramer) from any unreacted 4-c Fig. 3 (a) DLS spectra illustrating the differences in particle size (hydrodynamic-diameter) among the deprotected (N 3 ) 1 -RhMOP (green), the deprotected (alkyne) 1 -RhMOP (red), the MOP-dimer (violet), the MOP-tetramer (cyan) and the MOP-satellite (orange). (b and c) MALDI-TOF spectra (top) and DOSY-NMR spectra (bottom) of MOP-tetramer (b) and MOP-satellite (c). © 2024 The Author(s). Published by the Royal Society of Chemistry Chem. Sci.,2024,15, 7992–7998 | 7995 Edge Article Chemical Science Open Access Article. Published on 30 April 2024. Downloaded on 1/3/2025 1:42:55 PM. This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. View Article Online cluster or (N 3 ) 1 -RhMOP, the crude product was dissolved in basic water, and then ltered using a centrifugal lter with a molecular weight cut-offof 30 kDa. The MOP-tetramer was retained, whereas the (smaller) 4-c cluster and (N 3 ) 1 -RhMOP passed through the lter. The puried MOP-tetramer was characterised by MALDI-TOF, which conrmed the successful attachment of four MOPs to the 4-c cluster, as evidenced by a broad peak centred at 39 027 m/z, in agreement with the expected mass of a MOP-tetramer having a molecular formula of [[(COOH-BDC) 23 (BDC-PEG 38 -1H-1,2,3-triazol-4-yl-PEG 6 -BDC) 1 - Rh 24 ] 4 Rh 2 +H + ] + (39 047 ±1480 g mol −1 ) (Fig. 3b and S48†). Moreover, the 1 H-NMR spectrum of MOP-tetramer in basic D 2 O conrmed the expected ratio of aliphatic PEG protons to aromatic protons in the 1-c MOP and the 4-c cluster, which had the same diffusion coefficient of 5.5 ×10 −10 m 2 s −1 (Fig. 3b, S46 and S47†). Importantly, the higher oligomeric degree of MOPtetramer compared to MOP-dimer was corroborated analytically by its lower diffusion coefficient (5.5 ×10 −10 m 2 s −1 vs. 6.2 ×10 −10 m 2 s −1 ) and by its greater particle-size (7.2 ±0.6 nm vs. 6.3 ±1.1 nm), as revealed by DLS (Fig. 3a and S50†). Finally, to further extend the oligomeric degree of this family of MOP-based giant molecules, we sought to prepare a highly connected node. We reasoned that such a node could be synthesised from a cuboctahedral Rh-MOP, which can contain up to 24 reactive sites on its surface. Thus, a 24-c node was synthesised using a Rh-MOP with all its carboxylic acid groups available (hereaer, COOH 24 -RhMOP). This entailed attaching 24 NH 2 - PEG 6 -alkyne chains, via amide-coupling chemistry, onto the surface of the COOH 24 -RhMOP to afford a 24-c node (hereaer, (alkyne) 24 -RhMOP). MALDI-TOF and 1 H-NMR spectroscopy conrmed the quantitative functionalisation of COOH 24 -RhMOP into (alkyne) 24 Rh-MOP (Fig. S52–S55†). Next, 24-c (alkyne) 24 RhMOP was reacted with an excess of 1-c (N 3 ) 1 -RhMOP (240 mol eq. per (alkyne) 24 -RhMOP) in a CuAAC click reaction to yield a satellite-like, MOP-based, giant molecule. The reaction proceeded homogenously in a mixture of CH 2 Cl 2 /DMF (1 : 1), using the same CuAAC catalysts as above with the addition of tris- (hydroxypropyltriazolylmethyl)amine (THPTA), for up to 14 days. Note that the chelating agent THPTA was used to further accelerate the reaction. 46,47 The solvent was removed in vacuo to afford the crude product, which was then treated with TBAF to yield a deprotected, satellite-like molecule (hereaer, MOP-satellite) in which all the peripheral MOPs contained 23 surface carboxylicacid groups available for further reactions. MOP-satellite is soluble in basic water and could be separated from unreacted (N 3 ) 1 -RhMOPs using a centrifugal lter with a molecular weight cut-offof 50 kDa. The isolated, puried MOP-satellite was rst analysed through mass spectrometry, which revealed a peak centred at 107 346 m/z, which we ascribed to a satellite structure having 10 peripheral MOPs and a molecular formula of [[((COOH-BDC) 23 (BDC-PEG 38 -1H-1,2,3-triazol-4-yl-PEG 6 -BDC) 1 - Rh 24 ) 10 (alkyne-PEG 6 -BDC) 14 Rh 24 ]+H + ] + (expected molecular weight: 107 678 ±3700 g mol −1 ; Fig. 3c and S59†). This molecular composition was further supported by the 1 H-NMR spectrum of the MOP-satellite in basic D 2 O, in which the ratio of aromatic protons to aliphatic PEG protons was 0.39; in agreement with the expected value for a satellite with 10 peripheral MOPs (0.41) (Fig. S57†). The aromatic and aliphatic signals displayed the same diffusion coefficient of 4.7 ×10 −11 m 2 s −1 (Fig. 3c and S58†), which is the smallest value among those of the synthesised oligomeric MOP-based molecules, consistent with the MOP-satellite having the highest oligomeric degree and the largest molecule size (calculated: 8.6 nm; DLS value: 9.6 ±0.8 nm (Fig. 3a and S61†). Finally, we also analysed the Na(I)toRh(II) ratio of the fully deprotonated MOP-satellite salt through inductively coupled plasma mass spectrometry (ICP-MS). The experimentally observed ratio of Na : Rh molar ratio was 1.19, which agrees with the expected value (1.15) (Table S1†). Study of the adsorption capabilities Having prepared a family of giant oligomeric MOP-based molecules of increasing oligomeric degree, we next endeavoured to explore the functionality of the intrinsic voids stemming from their respective MOP cavities. We had envisioned that their oligomerisation would give rise to the rst set of intrinsically porous oligomeric molecules. To demonstrate the permanent porosity of the three oligomeric MOP-based molecules, we subjected them to CO 2 -adsorption/desorption experiments at 195 K (Fig. S63–S68†). The measurements conrmed that each giant molecule had retained the microporosity of its parent MOP, as evidenced by the corresponding isotherms, all of which exhibit a type-1 shape (Fig. 4). These isotherms were characterized by a sharp increase in the low-pressure range, followed by a plateau in the middle-to-high pressure range. This shape of the isotherm is consistent with the type-1 adsorption characteristic of microporous materials. The total CO 2 -uptakes at 1 bar were: 54.4 mol mol −1 MOP unit (MOP-dimer), 30.8 mol mol −1 MOP unit (MOP-tetramer), and 35.1 mol mol −1 MOP unit Fig. 4 Isotherms of CO 2 -adsorption at 195 K for the deprotected (N 3 ) 1 -RhMOP (green), the deprotected (alkyne) 1 -RhMOP (red), the (alkyne) 24 -RhMOP (black), the MOP-dimer (purple), the MOP-tetramer (blue), and the MOP-satellite (orange). 7996 |Chem. Sci.,2024,15, 7992–7998 © 2024 The Author(s). Published by the Royal Society of Chemistry Chemical Science Edge Article Open Access Article. Published on 30 April 2024. Downloaded on 1/3/2025 1:42:55 PM. This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. View Article Online (MOP-satellite). We ascribed the higher uptake of MOP-dimer to its lack of dangling free PEG chains, which can block porosity; indeed, such chains are found in MOP-satellite. It can also be attributed to its absence of non-porous structuring units (i.e. cluster); for example, these units are found in the MOPtetramer. Interestingly, CO 2 -uptake was markedly higher for all the giant oligomeric molecules than for the deprotected 1-c (N 3 ) 1 -RhMOP (6.1 mol mol −1 MOP unit), the deprotected 1-c (alkyne) 1 -RhMOP (8.3 mol mol −1 MOP unit) and the 24-c (alkyne) 24 -RhMOP (3.6 mol mol −1 MOP unit) precursors. We ascribed the greater porosity of the oligomeric molecules relative to their precursors to fact that the PEG chains are less mobile when they act as linkers in the former, than when they are dangling from the surface of the latter. Conclusions In summary, we have synthesised, characterised, and functionally validated a new class of giant oligomeric porous cage-based molecules. Namely, we developed a new method for the stepwise assembly of individual MOP cavities into oligomeric molecules, based on two factors that enable oligomerisation, rather than polymerisation. Firstly, the use of 1-c MOPs as building blocks enables termination of the linkage reaction at the oligomeric regime. Secondly, the use of an orthogonal reaction (in our case, CuAAC click chemistry) to link these blocks with other 1-c MOPs or with 4-c nodes or 24-c MOPs to yield molecules of increasing oligomeric degrees, precluding self-condensation between the precursors. Furthermore, gas-sorption experiments revealed that the giant oligomeric molecules retain the intrinsic porosity of the cavities of their parent MOP. We are condent that our results should inform the future design of new porous materials that will occupy the chemical and dimensional space between purely monomeric cavities and extended networks. Author contributions A. C. M.: conceptualization, methodology, investigation, and writing-original dra. C. v. B.: methodology and investigation. L. H. L.: validation and investigation. A. C. S: funding acquisition, conceptualization, supervision and writing-review and editing. D. M.: funding acquisition, conceptualization, supervision and writing-review and editing. Conflicts of interest There are no conicts to declare. Acknowledgements This work has received funding from the Europa Excelencia grant (EUR2021-121997) and the Catalan AGAUR (project 2017 SGR 238). It was also funded by the CERCA Programme/ Generalitat de Catalunya. ICN2 is supported by the Severo Ochoa Centres of Excellence programme, Grant CEX2021001214-S, funded by MCIN/AEI/10.13039.501100011033. A. C. S. is indebted to the Ram´ on y Cajal Program (RYC2020-029749-I Fellowship). C. v. B. thanks the Austrian Science Fund (FWF), Erwin Schrödinger fellowship for supporting the project J 4637. Notes and references 1 S. Lee, H. Jeong, D. Nam, M. S. 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