We introduce click-controlled photouncaging, an innovative approach that synergizes click ligation with photocleavage to achieve biorthogonal, light-triggered bioactive molecule release across visible to near-infrared (NIR) wavelengths. Central to this approach is a novel amine protection and deprotection strategy utilizing Pt(IV) complexes. In this strategy, an azide-bearing clickable Pt(IV) moiety acts as a protecting group for amine-containing molecules (the ″cargo″) via a carbamate linkage. Subsequently, click ligation with a DBCO-tagged fluorescent antenna positions the antenna near the Pt(IV) core, transforming it into a photoactive protecting group (PPG) that can be fine-tuned to respond to visible or NIR light. When exposed to light, the antenna drives the photoreduction of the Pt(IV) linker, triggering deprotection and subsequently releasing the cargo molecule. To validate this approach, three Pt(IV) complexes were synthesized featuring amine-containing fluorescent reporters (coumarin, BODIPY) and a therapeutic molecule (Exatecan), and their functionality was validated in solution and cell cultures. Overall, this work introduces a novel, user-friendly, and versatile chemical tool for bioorthogonal, light-controlled activation of molecules in complex biological environments.

Precise molecular activation with both analyte specificity and spatiotemporal control remains a major challenge in responsive diagnostics, targeted therapies, and the study of complex biological systems. Traditional photo-uncaging strategies offer excellent temporal resolution but suffer from limited tissue penetration and poor biological specificity, while analyte-responsive platforms provide molecular selectivity without external control. Here, we introduce sequence-responsive diagnostic uncaging-a unique approach that integrates nucleic acid recognition with near-infrared (NIR)-triggered molecular activation within a metal-nucleic acid scaffold. This platform is built upon a first-of-its-kind Pt(IV)-DNA molecular scaffold, modularly assembled via click chemistry, and integrates a Pt(IV)-caged reporter, a nucleic acid recognition domain, and an NIR antenna (e.g., IR800). Notably, DNA-mediated electron transfer (DNA-MET) provides a long-range ET pathway to direct photoreduction of the Pt(IV) centers, enabling "responsive uncaging" that occurs only upon hybridization with a fully complementary DNA or miRNA strand. Upon NIR irradiation, the duplexed nucleic acid system facilitates electron transfer from the excited antenna to Pt(IV), triggering the release of fluorescent reporters. Using two Pt(IV)-caged fluorophores (MCA and BDP), we demonstrate efficient uncaging and high sequence specificity in both solution and live cells. This platform offers a powerful and versatile photochemical tool that seamlessly bridges diagnostics and molecular activation, with broad implications for precision medicine, targeted drug delivery, and next-generation biosensing technologies.

ADVERTISEMENT RETURN TO ISSUEPREVReviewNEXTMetal–Organic Frameworks and Self-Assembled Supramolecular Coordination Complexes: Comparing and Contrasting the Design, Synthesis, and Functionality of Metal–Organic MaterialsTimothy R. Cook*, Yao-Rong Zheng, and Peter J. Stang*View Author Information Department of Chemistry, University of Utah, 315 South 1400 East, RM 2020, Salt Lake City, Utah 84112, United States*E-mail addresses: [email protected] (T.R.C.); [email protected] (P.J.S).Cite this: Chem. Rev. 2013, 113, 1, 734–777Publication Date (Web):November 2, 2012Publication History Received11 July 2012Published online2 November 2012Published inissue 9 January 2013https://pubs.acs.org/doi/10.1021/cr3002824https://doi.org/10.1021/cr3002824review-articleACS PublicationsCopyright © 2012 American Chemical SocietyRequest reuse permissionsArticle Views49336Altmetric-Citations2581LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose SUBJECTS:Chemical structure,Ligands,Materials,Metal organic frameworks,Metals Get e-Alerts

The multicomponent coordination-driven self-assembly of hexakis [4-(4-pyridyl)phenyl]benzene, cis-(PEt3)(2)Pt-II(OTf)(2), and amine- or maleimide-functionalized isophthalate forms discrete hexagonal prisms as single reaction products. The amino or maleimide groups decorating the isophthalate pillars of the prisms provide reactive sites for post-self-asssembly modifications. In this communication, we demonstrate that the hexagonal prisms can be functionalized without disrupting the prismatic cores, enabling the incorporation of new functionalities under mild conditions.

Post-self-assembly modifications of a discrete metal organic supramolecular structure have been developed. Such modifications allow the properties of the self-assembled supramolecular species to be changed in a simple and efficient manner (>90% yield). Initiated by the application of chemical stimuli, the post-self-assembly modifications described herein result in three distinct changes to the supramolecular system: an individual building-block component change, an overall structural modification, and a functional evolution of a [6+4] metal organic supramolecular structure. The three modifications have been carefully examined by a range of characterization methods, including NMR and UV-vis spectroscopy, electrospray ionization mass spectrometry, pulsed field gradient spin echo NMR measurements, electrochemical analysis, and computational simulations.

The design and preparation of novel M(3)L(2) trigonal cages via the coordination-driven self-assembly of preorganized metalloligands containing octahedral aluminum(III), gallium(III), or ruthenium(II) centers is described. When tritopic or dinuclear linear metalloligands and appropriate complementary subunits are employed, M(3)L(2) trigonal-bipyramidal and trigonal-prismatic cages are self-assembled under mild conditions. These three-dimensional cages were characterized with multinuclear NMR spectroscopy ((1)H and (31)P) and high-resolution electrospray ionization mass spectrometry. The structure of one such trigonal-prismatic cage, self-assembled from an arene ruthenium metalloligand, was confirmed via single-crystal X-ray crystallography. The fluorescent nature of these prisms, due to the presence of their electron-rich ethynyl functionalities, prompted photophysical studies, which revealed that electron-deficient nitroaromatics are effective quenchers of the cages' emission. Excited-state charge transfer from the prisms to the nitroaromatic substrates can be used as the basis for the development of selective and discriminatory turn-off fluorescent sensors for nitroaromatics.

The design and synthesis of coordinative supramolecular polygons with open binding sites is described. Coordination-driven self-assembly of 2,6-bis(pyridin-4-ylethynyl)pyridine with 60° and 120° organoplatinum acceptors results in quantitative formation of a supramolecular rhomboid and hexagon, respectively, both bearing open pyridyl binding sites. The structures were determined by multinuclear ((31)P and (1)H) NMR spectroscopy and electrospray ionization (ESI) mass spectrometry, along with a computational study.

We present a general strategy for the synthesis of stable 3-D metallosupramolecular tetragonal prisms in which multicomponent coordination-driven self-assembly allows for single supramolecular species to be formed. The appropriate stoichiometric combination of a tetraphenylethylene-based tetratopic donor (1), a linear dipyridine donor (2), and a 90 degrees platinum metal complex (3) affords tetragonal prisms (4) as single products. The compounds have been characterized by multinuclear NMR spectroscopy and electrospray ionization mass spectrometry. The size of the supramolecules was determined by pulsed-gradient spin-echo NMR and modeled with molecular force field simulation methods.

The construction of a new series of dendritic tris(crown ether) hexagons via coordination-driven self-assembly is described. Combining 120° crown ether-containing diplatinum(II) acceptors with 120° dendritic dipyridyl donors in a 1:1 ratio allows for the formation of a new family of dendritic triple crown ether derivatives with a hexagonal cavity in quantitative yields. The number and the position of these pendant groups can be precisely controlled on the hexagonal metallacycle. The structures of all dendritic multiple crown ether hexgaons are confirmed by multinuclear NMR ((1)H and (31)P), ESI-MS and ESI-TOF-MS, and elemental analysis. The complexation of these dendritic trivalent receptors with dibenzylammonium cations was investigated by (1)H NMR titration experiments. The thermodynamic binding constants between the receptors and guests were established by using the nonlinear least-squares fit method based on (1)H NMR titration experiments. It was found that the association constants of each assembly decrease correspondingly upon the increase of the generation of the dendrons from [G0] to [G3], which might be caused by the steric effect of the dendrons on host-guest complexation.

The coordination-driven self-assembly of supramolecular hexagonal prisms has been achieved upon mixing a hexakis[4-(4-pyridyl)phenyl]benzene donor ligand and carboxylate donor ligands such as sodium terephthalate, sodium (1,1'-biphenyl)-4,4'-dicarboxylate, sodium 4,4'-(diazene-1,2-diyl)dibenzoate, and 4,4'-dipyridyl with cis-Pt(PEt(3))(2)(OTf)(2) in a 1:3:6 ratio. Four assembled hexagonal prisms have been characterized by (31)P and (1)H NMR multinuclear spectroscopy as well as electrospray ionization mass spectrometry. Molecular force-field simulations provide the possible conformation and size of each structure.

The design and synthesis of novel three-dimensional (3-D) supramolecular dendrimers is described. The coordination-driven self-assembly of a 120 degrees diplatinum acceptor and tritopic pyridyl donors bearing [G-0]-[G-3] Fréchet-type dendrons results in a series of supramolecular dendrimers under mild conditions, possessing a robust adamantanoid core of well-defined shape and size. The assemblies were identified using multinuclear ((31)P and (1)H) NMR spectroscopy and electrospray ionization mass spectrometry, as well as pulsed-field-gradient spin-echo (PGSE) NMR measurement together with computational simulations. Isotopically resolved mass spectral data support the existence of the [6 + 4] assembly of adamantanoid dendrimers, and the NMR results are consistent with the formation of these symmetrical assemblies. PGSE NMR measurements together with MMFF force-field modeling clearly reveal the structural feature of the 3-D supramolecular dendrimers with varying sizes.

The design and synthesis of a new class of dendritic multiferrocenyl hexagons have been achieved via [3+3] coordination-driven self-assembly. The relative distribution of dendritic and ferrocenyl subunits on the periphery of supramolecular metallocycles can be precisely controlled. The structures of all compounds are confirmed by multinuclear NMR, ESI-MS/ESI-TOF-MS, and elemental analysis. The electrochemical properties of the newly designed dendritic multiferrocenyl complexes have been studied through cyclic voltammetry investigation.

The design and synthesis of coordinative truncated tetrahedra is described. The coordination-driven self-assembly of a truncated tetrahedron was achieved using 90° organoplatinum acceptors and a hexapyridyl ligand with six-fold symmetry under mild conditions. This tetrahedron can act as a host toward 1,3,5-triphenylbenzene. The truncated tetrahedral structures and the host-guest complex were identified using multinuclear ((31)P and (1)H) NMR spectroscopy, electrospray ionization mass spectrometry, X-ray crystallography, and pulsed-field-gradient spin-echo NMR, along with computational simulations.

A novel approach toward the construction of multicomponent two-dimensional (2-D) and three-dimensional (3-D) metallosupramolecules is reported. Simply by mixing carboxylate and pyridyl ligands with cis-Pt(PEt3)2(OTf)2 in a proper ratio, coordination-driven self-assembly occurs, allowing for the selective generation of discrete multicomponent structures via charge separation on the metal centers. Using this method, a variety of 2-D rectangles and 3-D prisms were prepared under mild conditions. Moreover, multicomponent self-assembly can also be achieved by supramolecule-to-supramolecule transformations. The products were characterized by 31P and 1H multinuclear NMR spectroscopy, electrospray ionization mass spectrometry, and pulsed-field-gradient spin echo NMR techniques together with computational simulations.

The fluorescence behaviours of a chemical-sensitive fluorescent molecule 1,2-di[5-methoxy-2-(2-pyridiyl)thiazoyl]ethyne (DMPTE) at different protonation and coordination states were studied. Upon addition of protons, metal ions and other chemicals, the fluorescent states can be switched reversibly. On the basis of the changes of fluorescence output signals from particular wavelengths in response to different combination sets of two particular external stimuli, the entire set of 2-bit Boolean binary logic functions were realized at the molecular level, including PASS 0, PASS 1, YES, NOT, OR, NOR, INHIBIT, IMPLICATION, AND, NAND, XOR, XNOR, and different logic functions were integrated reconfigurably within DMPTE. Besides, starting from the same initial state, a series of three-input logic gates and circuits were also constructed. Furthermore, the stepwise recognition process of DMPTE to different chemical input signals can also be utilized to distinguish different input sequences, thus a molecular keypad lock that authenticates three-digit password entries is indicated.