Gas-phase structure of polymer ions: Tying together theoretical approaches and ion mobility spectrometry.

An increasing number of studies take advantage of ion mobility spectrometry (IMS) coupled to mass spectrometry (IMS-MS) to investigate the spatial structure of gaseous ions. Synthetic polymers occupy a unique place in the field of IMS-MS. Indeed, due to their intrinsic dispersity, they offer a broad range of homologous ions with different lengths. To help rationalize experimental data, various theoretical approaches have been described. First, the study of trend lines is proposed to derive physicochemical and structural parameters. However, the evaluation of data fitting reflects the overall behavior of the ions without reflecting specific information on their conformation. Atomistic simulations constitute another approach that provide accurate information about the ion shape. The overall scope of this review is dedicated to the synergy between IMS-MS and theoretical approaches, including computational chemistry, demonstrating the essential role they play to fully understand/interpret IMS-MS data.

Site Selectivity of Peptoids as Azobenzene Scaffold for Molecular Solar Thermal Energy Storage.

Storing solar energy is a key challenge in modern science. MOlecular Solar Thermal (MOST) systems, in particular those based on azobenzene switches, have received great interest in the last decades. The energy storage properties of azobenzene (t1/2 <4 days; ΔH~270 kJ/kg) must be improved for future applications. Herein, we introduce peptoids as programmable supramolecular scaffolds to improve the energy storage properties of azobenzene-based MOST systems. We demonstrate with 3-unit peptoids bearing a single azobenzene chromophore that dynamics of the MOST systems can be tuned depending on the anchoring position of the photochromic unit on the macromolecular backbone. We measured a remarkable increase of the half-life of the metastable form up to 14 days at 20 °C for a specific anchoring site, significantly higher than the isolated azobenzene moiety, thus opening new perspectives for MOST development. We also highlight that liquid chromatography coupled to mass spectrometry does not only enable to monitor the different stereoisomers during the photoisomerization process as traditionally done, but also allows to determine the thermal back-isomerization kinetics.

Influence of the dispersity and molar mass distribution of conjugated polymers on the aggregation type and subsequent chiral expression.

This study aims to determine the influence of the dispersity on the aggregation of conjugated polymers and their subsequent chiral expression. Dispersity has been thoroughly investigated for industrial polymerizations, but research on conjugated polymers is lacking. Nonetheless, knowledge thereof is crucial for controlling the aggregation type (type I versus type II) and its influence is therefore investigated. For that purpose, a series of polymers is synthesized via metered initiator addition, resulting in dispersities ranging from 1.18-1.56. The lower dispersity polymers yield type II aggregates and the resulting symmetrical electronic circular dichroism (ECD) spectra while the higher dispersity polymers are predominantly type I due to the longer chains effectively acting as a seed and therefore yield asymmetrical ECD spectra. Furthermore, a monomodal and bimodal molar mass distribution of similar dispersity are compared, demonstrating that bimodal distributions show both aggregation types and therefore more disorder, leading to a decrease in chiral expression.

The expression of chirality in linked poly(thiophene)s.

Conjugated polymers have demonstrated to express chirality, for instance, by strong circular dichroism (CD). However, the shape and intensity of the spectra can be quite different and are very difficult to predict. Molecular irregularity, star-shapes, and linking polymers have demonstrated to affect the CD, often in a positive way. In this research, we design two different chiral arms, in which the molecular irregularity results in a significantly different CD. Next, the arms are coupled to a linear core in all possible combinations. In this way, we demonstrate that rather small irregularities and linking arms to a central core increases CD, whereas heterogenous combinations result in smaller CD.

Synthesis and Characterization of Tetraphenylethene AIEgen-Based Push-Pull Chromophores for Photothermal Applications: Could the Cycloaddition-Retroelectrocyclization Click Reaction Make Any Molecule Photothermally Active?

Three new tetraphenylethene (TPE) push-pull chromophores exhibiting strong intramolecular charge transfer (ICT) are described. They were obtained via [2 + 2] cycloaddition-retroelectrocyclization (CA-RE) click reactions on an electron-rich alkyne-tetrafunctionalized TPE (TPE-alkyne) using both 1,1,2,2-tetracyanoethene (TCNE), 7,7,8,8-tetracyanoquinodimethane (TCNQ) and 2,3,5,6-tetrafluoro-7,7,8,8-tetracyanoquinodimethane (F4-TCNQ) as electron-deficient alkenes. Only the starting TPE-alkyne displayed significant AIE behavior, whereas for TPE-TCNE, a faint effect was observed, and for TPE-TCNQ and TPE-F4-TCNQ, no fluorescence was observed in any conditions. The main ICT bands that dominate the UV-Visible absorption spectra underwent a pronounced red-shift beyond the near-infrared (NIR) region for TPE-F4-TCNQ. Based on TD-DFT calculations, it was shown that the ICT character shown by the compounds exclusively originated from the clicked moieties independently of the nature of the central molecular platform. Photothermal (PT) studies conducted on both TPE-TCNQ and TPE-F4-TCNQ in the solid state revealed excellent properties, especially for TPE-F4-TCNQ. These results indicated that CA-RE reaction of TCNQ or F4-TCNQ with donor-substituted are promising candidates for PT applications.

On the Conformation of Anionic Peptoids in the Gas Phase.

Although N-(S)-phenylethyl peptoids are known to adopt helical structures in solutions, the corresponding positively charged ions lose their helical structure during the transfer from the solution to the gas phase due to the so-called charge solvation effect. We, here, considered negatively charged peptoids to investigate by ion mobility spectrometry-mass spectrometry whether the structural changes described in the positive ionization mode can be circumvented in the negative mode by a fine-tuning of the peptoid sequence, that is, by positioning the negative charge at the positive side of the helical peptoid macrodipole. N-(S)-(1-carboxy-2-phenylethyl) (Nscp) and N-(S)-phenylethyl (Nspe) were selected as the negative charge carrier and as the helix inductor, respectively. We, here, report the results of a joint theoretical and experimental study demonstrating that the structures adopted by the NspenNscp anions remain compactly folded in the gas phase for chains containing up to 10 residues, whereas no evidence of the presence of a helical structure was obtained, even if, for selected sequences and lengths, different gas phase conformations are detected.

Impact of the Hydrolysis and Methanolysis of Bidesmosidic Chenopodium quinoa Saponins on Their Hemolytic Activity.

Saponins are specific metabolites abundantly present in plants and several marine animals. Their high cytotoxicity is associated with their membranolytic properties, i.e., their propensity to disrupt cell membranes upon incorporation. As such, saponins are highly attractive for numerous applications, provided the relation between their molecular structures and their biological activities is understood at the molecular level. In the present investigation, we focused on the bidesmosidic saponins extracted from the quinoa husk, whose saccharidic chains are appended on the aglycone via two different linkages, a glycosidic bond, and an ester function. The later position is sensitive to chemical modifications, such as hydrolysis and methanolysis. We prepared and characterized three sets of saponins using mass spectrometry: (i) bidesmosidic saponins directly extracted from the ground husk, (ii) monodesmosidic saponins with a carboxylic acid group, and (iii) monodesmosidic saponins with a methyl ester function. The impact of the structural modifications on the membranolytic activity of the saponins was assayed based on the determination of their hemolytic activity. The natural bidesmosidic saponins do not present any hemolytic activity even at the highest tested concentration (500 µg·mL-1). Hydrolyzed saponins already degrade erythrocytes at 20 µg·mL-1, whereas 100 µg·mL-1 of transesterified saponins is needed to induce detectable activity. The observation that monodesmosidic saponins, hydrolyzed or transesterified, are much more active against erythrocytes than the bidesmosidic ones confirms that bidesmosidic saponins are likely to be the dormant form of saponins in plants. Additionally, the observation that negatively charged saponins, i.e., the hydrolyzed ones, are more hemolytic than the neutral ones could be related to the red blood cell membrane structure.

Helical Peptoid Ions in the Gas Phase: Thwarting the Charge Solvation Effect by H-Bond Compensation.

Folding and unfolding processes are key aspects that should be mastered for the design of foldamer molecules for targeted applications. In contrast to the solution phase, in vacuo conditions represent a well-defined environment to analyze the intramolecular interactions that largely control the folding/unfolding dynamics. Ion mobility mass spectrometry coupled to theoretical modeling represents an efficient method to decipher the spatial structures of gaseous ions, including foldamers. However, charge solvation typically compacts the ion structure in the absence of strong stabilizing secondary interactions. This is the case in peptoids that are synthetic peptide regioisomers whose side chains are connected to the nitrogen atoms of the backbone instead of α-carbon as in peptides, thus implying the absence of H-bonds among the core units of the backbone. A recent work indeed reported that helical peptoids based on Nspe units formed in solution do not retain their secondary structure when transferred to the gas phase upon electrospray ionization (ESI). In this context, we demonstrate here that the helical structure of peptoids bearing (S)-N-(1-carboxy-2-phenylethyl) bulky side chains (Nscp) is largely preserved in the gas phase by the creation of a hydrogen bond network, induced by the presence of carboxylic moieties, that compensates for the charge solvation process.

Organocatalytic Synthesis of Alkyne-Functional Aliphatic Polycarbonates via Ring-Opening Polymerization of an Eight-Membered-N-Cyclic Carbonate.

The synthesis of well-defined propargyl-functional aliphatic polycarbonates is achieved via the organocatalytic ring-opening polymerization of prop-2-yn-1-yl 2-oxo-1,3,6-dioxazocane-6-carboxylate (P-8NC) using a wide variety of commercially available or readily made, shelf-stable organocatalysts. The resulting homopolymers show low dispersities and end-group fidelity, with the versatility of the system being demonstrated by the synthesis of telechelic copolymers and block copolymers with molar mass up to 40 kDa.

Helicity of Peptoid Ions in the Gas Phase.

Peptoids are attractive substitutes for peptides in several research areas, especially when they adopt a helical structure. The chain-size evolution of the secondary structure of the widely studied (S)-N-1-phenylethyl peptoids is here analyzed by means of the ion mobility mass spectrometry technique increasingly used as a powerful analytical tool and is further supported by theoretical modeling. We conclude that the helical shape of the peptoids prevailing in solution is lost in the gas phase by the need to screen the positive charge borne by the peptoid even though the collisional cross sections are close to the values expected for helical systems. We further illustrate that trend line analyses predicting molecular shapes from fits of the size evolution of cross sections can be very misleading since they critically depend on the range of polymerization degrees under study.

Limitations of ion mobility spectrometry-mass spectrometry for the relative quantification of architectural isomeric polymers: A case study.

Since their discovery, cyclic polymers have attracted great interest because of their unique properties. Today, the preparation of these macrocyclic structures still remains a challenge for polymer chemists, and most of the preparation pathways lead to an inescapable contamination by linear by-products. As the properties of the polymers are closely related to their structure, it is of prime importance to be able to assess the architectural purity of a sample. METHODS: In this work, the suitability of ion mobility spectrometry-mass spectrometry (IMS-MS) for the quantification of two isomers was investigated. A cyclic poly(L-lactide) was prepared through photodimerization of its linear homologue. Since IMS-MS can be used to differentiate cyclic polymer ions from their linear analogues because of their more compact three-dimensional conformation, the present work envisaged the use of IMS-MS for the quantification of residual linear polymers within the cyclic polymer sample. RESULTS: Using the standard addition method to plot calibration curves, the fraction of linear contaminants in the sample was determined. By doing so, unrealistically high values of contamination were measured. CONCLUSIONS: These results were explained by an ionization efficiency issue. This work underlines some intrinsic limitations when using IMS-MS in the context of the relative quantification of isomers having different ionization efficiencies. Nevertheless, the linear-to-cyclic ratio can be roughly estimated by this method.

Efficient Convergent Energy Transfer in a Stereoisomerically Pure Heptanuclear Luminescent Terpyridine-Based Ru(II)-Os(II) Dendrimer.

The stereoisomerically pure synthesis of a novel heptanuclear Ru(II)-Os(II) antenna bearing multitopic terpyridine ligands is reported. An unambiguous structural characterization was obtained by 1H NMR spectroscopy and ion mobility spectrometry (IMS-MS). The heptanuclear complex exhibits large molar absorption coefficients (77900 M-1 cm-1 at 497 nm) and undergoes unitary, downhill, convergent energy transfer from the peripheral Ru(II) subunits to the central Os(II) that displays photoluminescence with a lifetime (τ = 161 ns) competent for diffusional excited-state electron transfer reactivity in solution.

Effects of electrospray mechanisms and structural relaxation on polylactide ion conformations in the gas phase: insights from ion mobility spectrometry and molecular dynamics simulations.

Recent advances in molecular dynamics (MD) simulations have made it possible to examine the behavior of large charged droplets that contain analytes such as proteins or polymers, thereby providing insights into electrospray ionization (ESI) mechanisms. In the present study, we use this approach to investigate the release of polylactide (PLA) ions from water/acetonitrile ESI droplets. We found that cationized gaseous PLA ions can be formed via various competing pathways. Some MD runs showed extrusion and subsequent separation of polymer chains from the droplet, as envisioned by the chain ejection model (CEM). On other occasions the PLA chains remained inside the droplets and were released after solvent evaporation to dryness, consistent with the charge residue model (CRM). Following their release from ESI droplets, the nascent gaseous PLA ions were subjected to structural relaxation for several µs in vacuo. The MD conformations generated in this way for various PLA charge states compared favorably to experimental results obtained by ion mobility spectrometry-mass spectrometry (IMS-MS). The structures of all PLA ions evolved during relaxation in the gas phase. However, some macroion species retained features that resembled their nascent structures. For this subset of ions, the IMS-MS response appears to be strongly correlated with the ESI release mechanism (CEM vs. CRM). The former favored extended structures, whereas the latter preferentially generated compact conformers.

A New Class of Rigid Multi(azobenzene) Switches Featuring Electronic Decoupling: Unravelling the Isomerization in Individual Photochromes.

We report a novel class of star-shaped multiazobenzene photoswitches comprising individual photochromes connected to a central trisubstituted 1,3,5-benzene core. The unique design of such C3-symmetric molecules, consisting of conformationally rigid and pseudoplanar scaffolds, made it possible to explore the role of electronic decoupling in the isomerization of the individual azobenzene units. The design of our tris-, bis-, and mono(azobenzene) compounds limits the π-conjugation between the switches belonging to the same molecule, thus enabling the efficient and independent isomerization of each photochrome. An in-depth experimental insight by making use of different complementary techniques such as UV-vis absorption spectroscopy, high performance liquid chromatography, and advanced mass spectrometry methods as ion mobility revealed an almost complete absence of electronic delocalization. Such evidence was further supported by both experimental (electrochemistry, kinetical analysis) and theoretical (DFT calculations) analyses. The electronic decoupling provided by this molecular design guarantees a remarkably efficient photoswitching of all azobenzenes, as evidenced by their photoisomerization quantum yields, as well as by the Z-rich UV photostationary states. Ion mobility mass spectrometry was exploited for the first time to study multiphotochromic compounds revealing the occurrence of a large molecular shape change in such rigid star-shaped azobenzene derivatives. In view of their high structural rigidity and efficient isomerization, our multiazobenzene photoswitches can be used as key components for the fabrication of complex stimuli-responsive porous materials.

Converging Energy Transfer in Polynuclear Ru(II) Multiterpyridine Complexes: Significant Enhancement of Luminescent Properties.

Ruthenium-based complexes are widely used as photocatalysts, as photosensitizers, or as building blocks for supramolecular assemblies. In the field of solar energy conversion, building light harvesting antenna is of prime interest. Nevertheless, collecting light is mandatory but not sufficient; once collected and transferred, the exciton has to be long-lived enough to be transferred to a catalytic site. If Ru(II) terpyridine complexes are prime building blocks for structural reasons, the short lifetime of their excited state prevents their use as a harvesting center in light antennae. In this paper, we present new polynuclear assemblies, based on Ru(II)-terpyridine units where delocalization of the excited state is combined with an antenna effect. As a consequence, complexes C1-C3 display long-lived excited states compared to [Ru(tpy)2]2+, making them promising efficient antenna building blocks to be connected to a final acceptor or a catalytic center.

Trifluoromethyl-Substituted Iridium(III) Complexes: From Photophysics to Photooxidation of a Biological Target.

Photodynamic therapeutic agents are of key interest in developing new strategies to develop more specific and efficient anticancer treatments. In comparison to classical chemotherapeutic agents, the activity of photodynamic therapeutic compounds can be finely controlled thanks to the light triggering of their photoreactivity. The development of type I photosensitizing agents, which do not rely on the production of ROS, is highly desirable. In this context, we developed new iridium(III) complexes which are able to photoreact with biomolecules; namely, our Ir(III) complexes can oxidize guanine residues under visible light irradiation. We report the synthesis and extensive photophysical characterization of four new Ir(III) complexes, [Ir(ppyCF3)2(N^N)]+ [ppyCF3 = 2-(3,5-bis(trifluoromethyl)phenyl)pyridine) and N^N = 2,2'-dipyridyl (bpy); 2-(pyridin-2-yl)pyrazine (pzpy); 2,2'-bipyrazine (bpz); 1,4,5,8-tetraazaphenanthrene (TAP)]. In addition to an extensive experimental and theoretical study of the photophysics of these complexes, we characterize their photoreactivity toward model redox-active targets and the relevant biological target, the guanine base. We demonstrate that photoinduced electron transfer takes place between the excited Ir(III) complex and guanine which leads to the formation of stable photoproducts, indicating that the targeted guanine is irreversibly damaged. These results pave the way to the elaboration of new type I photosensitizers for targeting cancerous cells.

Synthesis and photophysical studies of a multivalent photoreactive RuII-calix[4]arene complex bearing RGD-containing cyclopentapeptides.

Photoactive ruthenium-based complexes are actively studied for their biological applications as potential theragnostic agents against cancer. One major issue of these inorganic complexes is to penetrate inside cells in order to fulfil their function, either sensing the internal cell environment or exert a photocytotoxic activity. The use of lipophilic ligands allows the corresponding ruthenium complexes to passively diffuse inside cells but limits their structural and photophysical properties. Moreover, this strategy does not provide any cell selectivity. This limitation is also faced by complexes anchored on cell-penetrating peptides. In order to provide a selective cell targeting, we developed a multivalent system composed of a photoreactive ruthenium(II) complex tethered to a calix[4]arene platform bearing multiple RGD-containing cyclopentapeptides. Extensive photophysical and photochemical characterizations of this Ru(II)-calixarene conjugate as well as the study of its photoreactivity in the presence of guanosine monophosphate have been achieved. The results show that the ruthenium complex should be able to perform efficiently its photoinduced cytotoxic activity, once incorporated into targeted cancer cells thanks to the multivalent platform.

Dynamic Iminoboronate-Based Boroxine Chemistry for the Design of Ambient Humidity-Sensitive Self-Healing Polymers.

Developing intrinsic self-healing polymeric materials is of great interest nowadays to extend material lifetime and/or prevent the replacement of damaged pieces. Spontaneously humidity-sensitive healable polymer network built around dynamic covalent B-O bonds was templated by using iminoboronate-based boroxine derivatives. Taking advantage of the dynamic boroxine/boronic acid equilibrium and iminoboronate chemistry, it is possible to construct polymeric materials able to self-heal without requiring any energy-demanding external activation. Interestingly, this novel family of iminoboronate adduct-based materials can be readily produced by a relatively simple and straightforward synthesis between boronic acid and diamine-based compounds, paving the way to coatings that are self-healable at ambient humidity.

Influence of Equilibration Time in Solution on the Inclusion/Exclusion Topology Ratio of Host-Guest Complexes Probed by Ion Mobility and Collision-Induced Dissociation.

Host-guest complexes are formed by the creation of multiple noncovalent bonds between a large molecule (the host) and smaller molecule(s) or ion(s) (the guest(s)). Ion-mobility separation coupled with mass spectrometry nowadays represents an ideal tool to assess whether the host-guest complexes, when transferred to the gas phase upon electrospray ionization, possess an exclusion or inclusion nature. Nevertheless, the influence of the solution conditions on the nature of the observed gas-phase ions is often not considered. In the specific case of inclusion complexes, kinetic considerations must be taken into account beside thermodynamics; the guest ingression within the host cavity can be characterized by slow kinetics, which makes the complexation reaction kinetically driven on the timescale of the experiment. This is particularly the case for the cucurbituril family of macrocyclic host molecules. Herein, we selected para-phenylenediamine and cucurbit[6]uril as a model system to demonstrate, by means of ion mobility and collision-induced dissociation measurements, that the inclusion/exclusion topology ratio varies as a function of the equilibration time in solution prior to the electrospray process.

Energy-resolved collision-induced dissociation of non-covalent ions: charge- and guest-dependence of decomplexation reaction efficiencies.

Supramolecular chemistry, and especially host-guest chemistry, has been the subject of great interest in the past few decades leading to the synthesis of host cage molecules such as calixarenes, cyclodextrins and more recently cucurbiturils. Mass spectrometry methods are increasingly used to decipher at the molecular level the non-covalent interactions between the different associated molecules. The present article illustrates that the association between mass spectrometry and computational chemistry techniques proves very complementary to depict the gas-phase dissociation processes of ionic non-covalent complexes when subjected to collisional activation. The selected system associates a nor-seco-cucurbit[10]uril bitopic receptor with different amino compounds (adamantylamine, para-xylylenediamine, and para-phenylenediamine). When subjected to CID experiments, the ternary complexes undergo fragmentation via dissociation of non-covalently bound partners. Interestingly, depending on their charge state, the collisionally excited complexes can selectively expel either a neutral guest molecule or a protonated guest molecule. Moreover, based on energy-resolved CID experiments, it is possible to evaluate the guest molecule dependence on the gas phase dissociation efficiency. We observed that the relative order of gas phase dissociation is charge state dependent, with the adamantylamine-containing complexes being the weakest when triply charged and the strongest when doubly charged. The energetics of the gas-phase dissociation reactions have been estimated by density functional theory (DFT) calculations. We succeeded in theoretically rationalizing the experimental collision-induced dissociation results with a special emphasis on: (i) the charge state of the expelled guest molecule and (ii) the nature of the guest molecule.