Tuning the Stability and Kinetics of Dioxazaborocanes.

We investigated the equilibrium reaction of boronic acid (BA), diethanolamines (DEA), and 1,3,6,2-dioxazaborocanes (DOAB) in aqueous solutions, both theoretically and experimentally. Our findings show that the association constant can be adjusted by substituting BA and DEA derivatives, ranging from 100 to 103 M-1, exhibiting a bell-shaped pH dependency. The highest stability was achieved when the pKa values of DEA and BA were closely matched. This approach enabled the preparation of a highly stable DOAB under physiological conditions. Furthermore, the hydrolysis kinetics of DOABs were controllable over a range of five orders of magnitude based on the substituent's steric effect. In the slowest case, this resulted in quasi-static stability with only 1% cleavage in the first hour, followed by a week-long cleavage period to reach equilibrium. These insights could establish a unique chemistry platform for designing scheduled cleavability on a day-to-week timescale, relevant to protein engineering, immunotherapy, and other smart drug delivery applications.

Block catiomers with flanking hydrolyzable tyrosinate groups enhance in vivo mRNA delivery via π-π stacking-assisted micellar assembly.

Messenger RNA (mRNA) therapeutics have recently demonstrated high clinical potential with the accelerated approval of SARS-CoV-2 vaccines. To fulfill the promise of unprecedented mRNA-based treatments, the development of safe and efficient carriers is still necessary to achieve effective delivery of mRNA. Herein, we prepared mRNA-loaded nanocarriers for enhanced in vivo delivery using biocompatible block copolymers having functional amino acid moieties for tunable interaction with mRNA. The block copolymers were based on flexible poly(ethylene glycol)-poly(glycerol) (PEG-PG) modified with glycine (Gly), leucine (Leu) or tyrosine (Tyr) via ester bonds to generate block catiomers. Moreover, the amino acids can be gradually detached from the block copolymers after ester bond hydrolyzation, avoiding cytotoxic effects. When mixed with mRNA, the block catiomers formed narrowly distributed polymeric micelles with high stability and enhanced delivery efficiency. Particularly, the micelles based on tyrosine-modified PEG-PG (PEG-PGTyr), which formed a polyion complex (PIC) and π-π stacking with mRNA, displayed excellent stability against polyanions and promoted mRNA integrity in serum. PEG-PGTyr-based micelles also increased the cellular uptake and the endosomal escape, promoting high protein expression both in vitro and in vivo. Furthermore, the PEG-PGTyr-based micelles significantly extended the half-life of the loaded mRNA after intravenous injection. Our results highlight the potential of PEG-PGTyr-based micelles as safe and effective carriers for mRNA, expediting the rational design of polymeric materials for enhanced mRNA delivery.

Collision cross-section analysis of self-assembled metallomacrocycle isomers and isobars via ion mobility mass spectrometry.

RATIONALE: Coordinatively driven self-assembly of transition metal ions and bidentate ligands gives rise to organometallic complexes that usually contain superimposed isobars, isomers, and conformers. In this study, the double dispersion ability of ion mobility mass spectrometry (IM-MS) was used to provide a comprehensive structural characterization of the self-assembled supramolecular complexes by their mass and charge, revealed by the MS event, and their shape and collision cross-section (Ω), revealed by the IM event. METHODS: Self-assembled complexes were synthesized by reacting a bis(terpyridine) ligand exhibiting a 60o dihedral angle between the two ligating terpyridine sites (T) with divalent Zn, Ni, Cd, or Fe. The products were isolated as (Metal2+ [T])n (PF6 )2n salts and analyzed using IM-MS after electrospray ionization (ESI) which produced several charge states from each n-mer, depending on the number of PF6 - anions lost upon ESI. Experimental Ω data, derived using IM-MS, and computational Ω predictions were used to elucidate the size and architecture of the complexes. RESULTS: Only macrocyclic dimers, trimers, and tetramers were observed with Cd2+ , whereas Zn2+ formed the same plus hexameric complexes. These two metals led to the simplest product distributions and no linear isomers. In sharp contrast, Ni2+ and Fe2+ formed all possible ring sizes from dimer to hexamer as well as various linear isomers. The experimental and theoretical Ω data indicated rather planar macrocyclic geometries for the dimers and trimers, twisted 3D architectures for the larger rings, and substantially larger sizes with spiral conformation for the linear congeners. Adding PF6 - to the same complex was found to mainly cause size contraction due to new stabilizing anion-cation interactions. CONCLUSIONS: Complete structural identification could be accomplished using ESI-IM-MS. Our results affirm that self-assembly with Cd2+ and Zn2+ proceeds through reversible equilibria that generate the thermodynamically most stable structures, encompassing exclusively macrocyclic architectures that readily accommodate the 60o ligand used. In contrast, complexation with Ni2+ and Fe2+ , which form stronger coordinative bonds, proceeds through kinetic control, leading to more complex mixtures and kinetically trapped less stable architectures, such as macrocyclic pentamers and linear isomers.

Superexchange in the fast lane - intramolecular electron transfer in a molecular triad occurs by conformationally gated superexchange.

Photoinduced electron transfer via hopping is generally considered to have a stronger temperature dependence than electron transfer via superexchange. However, in this work, an opposite trend of the temperature dependence is observed. This unexpected result is rationalized by considering the specific geometrical and electronic structure of the Ru-bis(terpyridine) photosensitizer.

Remote control of electronic coupling - modification of excited-state electron-transfer rates in Ru(tpy)2-based donor-acceptor systems by remote ligand design.

A comprehensive understanding of how the molecular structure influences the electronic coupling is crucial in optimizing (supra) molecular assemblies for photoinduced electron transfer. Here, we report that the electronic coupling underlying electron transfer from a phenothiazine donor to a photoexcited Ru(tpy)2 acceptor is modulated by substitution of the second (remote) tpy-ligand.

Coexistence of distinct intramolecular electron transfer pathways in polyoxometalate based molecular triads.

Polyoxometalate (POM)-associated charge-separated states, formed by the photoinduced oxidation of a covalently attached photosensitizer and reduction of the POM, have attracted much attention due to the remarkable catalytic properties of the reduced POMs. However, short lifetimes of the POM-associated charge-separated state, which in some cases lead to the backward electron transfer being more rapid than the formation of the charge-separated state itself, are generally observed. Recently, we reported on the first example of a relative long-lived (τ = 470 ns) charge-separated state in a Ru(ii) bis(terpyridine)-POM molecular dyad. In this manuscript, further studies on extended molecular structures - two molecular triads - which contain an additional electron donor, phenothiazine (PTZ) or π-extended tetrathiafulvalene (exTTF), are discussed. We show that the excitation of the photosensitizer leads to the population of two distinct MLCT states, which differ in the distribution of excess electron density on the two distinct tpy ligands. These two MLCT states decay separately and, thus, constitute the starting points for distinct intramolecular electron-transfer pathways leading to the simultaneous population of two partially charge-separated states, i.e. PTZ˙+-Ru(tpy)2˙--POM and PTZ-RuIII(tpy)2-POM˙-. These independent decay pathways are unaffected by the choice of the electron donor. Thus, the initial charge distribution within the coordination environment of the photocenter determines the nature of the subsequent (partially) charge separated state that is formed in the triads. These results might open new avenues to design molecular interfaces, in which the directionality of electron transfer can be tuned by the choice of initial excitation.

Direct detection of the photoinduced charge-separated state in a Ru(ii) bis(terpyridine)-polyoxometalate molecular dyad.

Observation of photoinduced intramolecular charge-separation is difficult for photosensitizer-POM dyads because of rapid backward electron transfer. We report here for the first time on a long-lived charge-separated state (τ = 470 ns) observed in a Ru(ii) bis(terpyridine)-based dyad. Charge-separation occurs despite virtually no driving force and the short intrinsic excited-state lifetime of the photosensitizer.

Energy versus Electron Transfer: Controlling the Excitation Transfer in Molecular Triads.

The photochemistry of RuII coordination compounds is generally discussed to originate from the lowest lying triplet metal-to-ligand charge-transfer state (3 MLCT). However, when heteroleptic complexes are considered, for example, in the design of molecular triads for efficient photoinduced charge separation, a complex structure of 1 MLCT states, which can be populated in a rather narrow spectral window (typically around 450 nm) is to be considered. In this contribution we show that the localization of MLCT excited states on different ligands can affect the following ps to ns decay pathways to an extent that by tuning the excitation wavelength, intermolecular energy transfer from a RuII -terpyridine unit to a fullerene acceptor can be favored over electron transfer within the molecular triad. These results might have important implications for the design of molecular dyads, triads, pentads and so forth with respect to a specifically targeted response of these complexes to photoexcitation.

Hybrid materials based on ruthenium and fullerene assemblies.

This review provides a detailed overview about the synthesis, properties and applications of all ruthenium-fullerene compounds reported within the last 25 years. The incorporation of ruthenium centers into fullerene compounds by organometallic, covalent or non-covalent bonds has led to a broad range of useful hybrid materials. By this approach novel compounds could be generated that feature the electron-donating and electron-accepting character of ruthenium complexes and fullerenes, respectively. Intramolecular interactions between both units could result in new, combined properties that were studied in the spotlight of emerging applications, such as photovoltaics or catalysis.

Efficient Energy Transfer and Metal Coupling in Cyanide-Bridged Heterodinuclear Complexes Based on (Bipyridine)(terpyridine)ruthenium(II) and (Phenylpyridine)iridium(III) Complexes.

We report a series of cyanide-bridged, heterodinuclear iridium(III)-ruthenium(II) complexes with the generalized formula [Ir((R2)2-ppy)2(CN)(µ-CN)Ru(bpy)(tpy-R1)]PF6 (ppy = 2-phenylpyridine, bpy = 2,2'-bipyridine, and tpy = 2,2':6',2″-terpyridine). The structural, spectroscopic, and electrochemical properties were analyzed in the context of variation of the electron-withdrawing (e.g., -F, -Br, -CHO) and -donating (e.g., -Me) and extended π-conjugated groups at several positions. In total, ten dinuclear complexes and the appropriate model complexes have been prepared. The iridium(III)-based emission is almost fully quenched in these complexes, and only the ruthenium(II)-based emission is observed, which indicates an efficient energy transfer toward the Ru center. Upon oxidation of the Ru center, the fluorinated complexes 2 exhibit a broad intervalence charge-transfer transition in the near-infrared region. The complexes are assigned to a weakly coupled class II system according to the Robin-Day classification. The electronic structure was evaluated by density functional theory (DFT) and time-dependent DFT calculations to corroborate the experimental data.

Energy transfer and formation of long-lived (3)MLCT states in multimetallic complexes with extended highly conjugated bis-terpyridyl ligands.

Multimetallic complexes with extended and highly conjugated bis-2,2':6',2''-terpyridyl bridging ligands, which present building blocks for coordination polymers, are investigated with respect to their ability to act as light-harvesting antennae. The investigated species combine Ru(II)- with Os(II)- and Fe(II)-terpyridyl chromophores, the latter acting as energy sinks. Due to the extended conjugated system the ligands are able to prolong the lifetime of the (3)MLCT states compared to unsubstituted terpyridyl species by delocalization and energetic stabilization of the (3)MLCT states. This concept is applied for the first time to Fe(II) terpyridyl species and results in an exceptionally long lifetime of 23 ps for the Fe(II) (3)MLCT state. While partial energy (>80%) transfer is observed between the Ru(II) and Fe(II) centers with a time-constant of 15 ps, excitation energy is transferred completely from the Ru(II) to the Os(II) center within the first 200 fs after excitation.

New ruthenium bis(terpyridine) methanofullerene and pyrrolidinofullerene complexes: synthesis and electrochemical and photophysical properties.

A series of terpyridine (tpy) methanofullerene and pyrrolidinofullerene dyads linked via p-phenylene or p-phenyleneethynylenephenylene (PEP) units is presented. The coordination to ruthenium(II) yields donor-bridge-acceptor assemblies with different lengths. Cyclic voltammetry and UV-vis and luminescence spectroscopy are applied to study the electronic interactions between the active moieties. It is shown that, upon light excitation of the ruthenium(II)-based (1)MLCT transition, the formed (3)MLCT state is readily quenched in the presence of C60. The photoinduced dynamics have been studied by transient absorption spectroscopy, which reveals fast depopulation of the (3)MLCT (73-406 ps). As a consequence, energy transfer occurs, populating a long-lived triplet state, which could be assigned to the (3)C60* state.