CB[7]- and CB[8]-Based [2]-(Pseudo)rotaxanes with Triphenylphosphonium-Capped Threads: Serendipitous Discovery of a New High-Affinity Binding Motif

Financiado para publicación en acceso aberto: Universidade da Coruña/CISUG[Abstract] The synthesis of new triphenylphosphonium-capped cucurbit[7]uril (CB[7])- and cucurbit[8]uril (CB[8])-based [2]rotaxanes was achieved by a simultaneous threading-capping strategy. While the use of CB[7] produced the designed [2]rotaxane, attempts to obtain the CB[8] analogue were unsuccessful due to the unexpected strong interaction found between the host and the phosphonium caps leading to pseudo-heteroternary host–guest complexes. This unusual binding motif has been extensively studied experimentally, with results in good agreement with those obtained by dispersion-corrected DFT methods.This research was supported by the Agencia Estatal de Investigación (PID2019-105272GB-I00) and Xunta de Galicia (ED431C 2018/39). I.N. thanks the MECD (FPU program). The authors are indebted to Centro de Supercomputación de Galicia (CESGA) for providing the computer facilitiesXunta de Galicia; ED431C 2018/3

Reversible Control of DNA Binding with Cucurbit[8]uril-Induced Supramolecular 4,4′-Bipyridinium–Peptide Dimers

Financiado para publicación en acceso aberto: Universidade da Coruña/CISUGThe Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acs.bioconjchem.1c00063[Abstract] Many cellular processes in living organisms are regulated by complex regulatory networks, built from noncovalent interactions between relatively few proteins that perform their functions by switching between homo- and heterooligomeric assemblies or mono- and bivalent states. Herein, we demonstrate that the conjugation of a 4,4′-bipyridinium scaffold to the basic region of the GCN₄ bZip transcription factor can be exploited to control the dimerization of the conjugate by formation of a supramolecular complex with cucurbit[8]uril. Importantly, this supramolecular complex is able to specifically recognize its target dsDNA, and this binding can be reversibly switched by the application of external stimuli.We are thankful for the funding received from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement No 851179), the Ministerio de Economía y Competitividad and Fondo Europeo de Desarrollo Regional (FEDER) (CTQ2016-75629-P), the Agencia Estatal de Investigación and FEDER (CTQ2017-89166-R and PID2019-105272GB-I00) and the Consellería de Educación, Universidade e Formación Profesional, Xunta de Galicia (ED431C 2018/39). P.N thanks the Ministerio de Ciencia, Innovación y Universidades for her PhD fellowship (FPU17/04357). E.P. thanks the UDC-Inditex InTalent Programme for her research contract and funding and the Xunta de Galicia for the Oportunius ProgrammeXunta de Galicia; ED431C 2018/39https://pubs.acs.org/doi/suppl/10.1021/acs.bioconjchem.1c00063/suppl_file/bc1c00063_si_001.pd

Self-Assembled Peptide–Inorganic Nanoparticle Superstructures: From Component Design to Applications

[Abstract] Peptides have become excellent platforms for the design of peptide–nanoparticle hybrid superstructures, owing to their self-assembly and binding/recognition capabilities. Morover, peptide sequences can be encoded and modified to finely tune the structure of the hybrid systems and pursue functionalities that hold promise in an array of high-end applications. This feature article summarizes the different methodologies that have been developed to obtain self-assembled peptide–inorganic nanoparticle hybrid architectures, and discusses how the proper encoding of the peptide sequences can be used for tailoring the architecture and/or functionality of the final systems. We also describe the applications of these hybrid superstructures in different fields, with a brief look at future possibilities towards the development of new functional hybrid materials.We are thankful for the funding received from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (grant agreement no. 851179), the Ministerio de Economía y Competitividad and Fondo Europeo de Desarrollo Regional (FEDER) (CTQ2016-75629-P), the Agencia Estatal de Investigación and FEDER (CTQ2017-89166-R) and the Consellería de Educación, Universidade e Formación Profesional, Xunta de Galicia (ED431C 2018/39). E. P. thanks the UDC-Inditex InTalent Programme for her research contract and funding and the Xunta de Galicia for the Oportunius ProgrammeXunta de Galicia; ED431C 2018/3

Stimuli-responsive metal-directed self-assembly of a ring-in-ring complex

[Abstract] Concentration, temperature and/or solvent polarity control the speciation on the metal-directed self-assembly of a ditopic pyridyl ligand L with cis-protected Pd(II) metal centers. This results into a controllable dynamic system, involving a [Pd2L2]6+ metallacycle and a [Pd4L4]12+ ring-in-ring complex.Ministerio de Economía y Competitividad; CTQ-201341097-PXunta de Galicia; EM2014/05

Solid-Phase Zincke Reaction for the Synthesis of Peptide-4,4′-bipyridinium Conjugates

Author accepted manuscript[Abstract] We present herein the development of a new synthetic strategy for the conjugation of 4,4′-bipyridinium derivatives into peptide scaffolds. The methodology, based on the development of a solid-phase version of the Zincke reaction between activated pyridinium salts and amines, is able to produce the desired conjugates in a straightforward fashion, with the bipyridinium units attached at the N-terminus of peptides or at Lys side chains of N-terminal acetylated peptides.This work has received financial support from the Ministerio de Economía y Competitividad and Fondo Europeo de Desarrollo Regional (FEDER) (CTQ2016-75629-P), Agencia Estatal de Investigación and FEDER (CTQ2017-89166-R), and the Consellería de Educación, Universidade e Formación Profesional, Xunta de Galicia (ED431C 2018/39)Xunta de Galicia; ED431C 2018/3

Amino Acid–Viologen Hybrids: Synthesis, Cucurbituril Host–Guest Chemistry, and Implementation on the Production of Peptides

Financiado para publicación en acceso aberto: Universidade da Coruña/CISUG[Abstract] We present herein the development of a series of viologen–amino acid hybrids, obtained in good yields either by successive alkylations of 4,4′-bipyridine, or by Zincke reactions followed by a second alkylation step. The potential of the obtained amino acids has been exemplified, either as typical guests of the curcubituril family of hosts (particularly CB[7]/[8]) or as suitable building blocks for the solution/solid-phase synthesis of two model tripeptides with the viologen core inserted within their sequences.The authors are grateful for the funding received from the Agencia Estatal de Investigación and FEDER (PID2019-105272GB-I00 and CTQ2017-89166-R), the Consellería de Educación, Universidade e Formación Profesional, Xunta de Galicia (ED431C 2018/39 and 508/2020), and the European Research Council (Grant Agreement No. 851179). I.N. thanks the MECD (FPU program) for financial support. E.P. thanks the Agencia Estatal de Investigación for her Ramón y Cajal contract (RYC2019-027199-I). Funding for open access charge: Universidade da Coruña/CISUGXunta de Galicia; ED431C 2018/39Xunta de Galicia; ED431C 508/202

Thinking Outside the Blue Box: Induced Fit within a Unique Self-Assembled Polycationic Cyclophane

This document is the Accepted Manuscript version of a Published Work that appeared in final form in Journal of the American Chemical Society.[Abstract] We present herein the development of a new polycationic molecular receptor, inspired by the ubiquitous cyclobis(paraquat-p-phenylene)cyclophane (“blue box”). Our analogue, the “white box”, has been easily self-assembled on a preparative scale in water, using a template-assisted process by acyl hydrazone bonding of complementary bis(pyridinium)xylylene tweezers, followed by kinetic trapping of the empty receptor. The obtained macrocycle was found to display a marked pH responsiveness in water, because of an abnormal acidity of the amide protons within its structure. Consequently, and because of the concurrence of rotational isomerism under acidic conditions (fixed at higher pH values), the compound was found to display a dual behavior as a conformationally locked/flexible molecular host, being able to recognize appropriate aromatic substrates, in a lock and key or induced fit fashion, by a conjunction of π–π, C–H···π, and, crucially, the hydrophobic effect.This research was supported by the Ministerio de Economía y Competitividad (MINECO FEDER, Grant CTQ2016-75629-P

Dimensional caging of polyiodides: cation-templated synthesis using bipyridinium salts

none8The potential of bipyridinium derivatives in the cation templated synthesis of polyiodides has been explored by applying the strategy of size-matching between cations and anions. Bipyridinium cations 1-4, bearing benzyl and functionalized benzyl pendants at nitrogen atoms, are able to template the selective formation of I(4)(2-) and I(3)(-) species. Thanks to the supramolecular space compartmentation induced by the benzyl pendants, the formation of I(4)(2-) and I(3)(-) is independent of the stoichiometry adopted in the crystallization procedure. Bipyridinium cation 5, bearing methyl pendants, is unable to induce space compartmentation and different polyiodides are obtained depending on the stoichiometry used in the crystallization process as the cation-anion size-matching alone does not control the polyiodide formation.M. D. Garcia; J. Marti-Rujas; P. Metrangolo; C. Peinador; T. Pilati; G. Resnati; G. Terraneo; M. UrsiniGarcia, M. D.; Marti Rujas, J.; Metrangolo, Pierangelo; Peinador, C.; Pilati, TULLIO MARIA; Resnati, Giuseppe; Terraneo, Giancarlo; Ursini, Maurizi

Aqueous Three-Component Self-Assembly of a Pseudo[1]rotaxane Using Hydrazone Bonds

[Abstract] We present herein the synthesis of a new polycationic pseudo[1]rotaxane, self-assembled in excellent yield through hydrazone bonds in aqueous media of three different aldehyde and hydrazine building blocks. A thermodynamically controlled process has been studied sequentially by analyzing the [1 + 1] reaction of a bisaldehyde and a trishydrazine leading to the macrocyclic part of the system, the ability of this species to act as a molecular receptor, the conversion of a hydrazine-pending cyclophane into the pseudo[1]rotaxane and, lastly, the one-pot [1 + 1 + 1] condensation process. The latter was found to smoothly produce the target molecule through an integrative social self-sorting process, a species that was found to behave in water as a discrete self-inclusion complex below 2.5 mM concentration and to form supramolecular aggregates in the 2.5–70 mM range. Furthermore, we demonstrate how the abnormal kinetic stability of the hydrazone bonds on the macrocycle annulus can be advantageously used for the conversion of the obtained pseudo[1]rotaxane into other exo-functionalized macrocyclic species.The authors are thankful for the funding received from the MCIN/AEI/10.13039/501100011033 and ERDF “A way of making Europe” (CTQ2016-75629-P, CTQ2017-89166-R and PID2019-105272GB-I00), the Consellería de Cultura, Educación e Universidade, Xunta de Galicia (ED431C 2018/39, ED431C 2022/39 and 508/2020), and the European Research Council (ERC) under the European Union’s Horizon 2020 Research and Innovation Programme (Grant Agreement No. 851179). P.C. and A.B.-G. thank the Consellería de Cultura, Educación e Universidade, Xunta de Galicia for their PhD and postdoctoral fellowships (ED481A-2020/019 and ED481B-2021-099, respectively). M.D.-A. thanks the Fundación Gil Dávila and the Ministerio de Universidades (FPU21/06302) for his PhD fellowships. E.P. thanks the MCIN/AEI/10.13039/501100011033 and ESF “Investing in your future” for her Ramón y Cajal contract (RYC2019-027199-I)Xunta de Galicia; ED431C 2018/39Xunta de Galicia; ED431C 2022/39Xunta de Galicia; 508/2020Xunta de Galicia; ED481A-2020/019Xunta de Galicia; ED481B-2021-09

Host-Guest Stimuli-Responsive Click Chemistry

Financiado para publicación en acceso aberto: Universidade da Coruña/CISUG[Abstract] Click chemistry has reached its maturity as the weapon of choice for the irreversible ligation of molecular fragments, with over 20 years of research resulting in the development or improvement of highly efficient kinetically controlled conjugation reactions. Nevertheless, traditional click reactions can be disadvantageous not only in terms of efficiency (side products, slow kinetics, air/water tolerance, etc.), but also because they completely avoid the possibility to reversibly produce and control bound/unbound states. Recently, non-covalent click chemistry has appeared as a more efficient alternative, in particular by using host-guest self-assembled systems of high thermodynamic stability and kinetic lability. This review discusses the implementation of molecular switches in the development of such non-covalent ligation processes, resulting in what we have termed stimuli-responsive click chemistry, in which the bound/unbound constitutional states of the system can be favored by external stimulation, in particular using host-guest complexes. As we exemplify with handpicked selected examples, these supramolecular systems are well suited for the development of human-controlled molecular conjugation, by coupling thermodynamically regulated processes with appropriate temporally resolved extrinsic control mechanisms, thus mimicking nature and advancing our efforts to develop a more function-oriented chemical synthesis.We are thankful for the funding received from the MCIN/AEI/10.13039/501100011033 and ERDF A way of making Europe (PID2022-137361NB-I00 and PID2022-142374NB-I00), the Consellería de Cultura, Educación e Universidade da Xunta de Galicia (ED431C 2022/39, and 508/2020), and the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (grant agreement no. 851179). M. D.-A. thanks the Ministerio de Universidades for his predoctoral fellowship (FPU21/06302), A. B.-G. thanks the Consellería de Cultura, Educación e Universidade, Xunta de Galicia for his postdoctoral fellowship (ED481B-2021-099), and E. P. thanks the MCIN/AEI/10.13039/501100011033 and ESF Investing in your future for her Ramón y Cajal contract (RYC2019-027199-I). Funding for open access charge: Universidade da Coruña/CISUGXunta de Galicia; ED431C 2022/39Xunta de Galicia; 508/2020Xunta de Galicia; ED481B-2021-09