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Novel optical pump-push – photocurrent probe ultrafast spectroscopy experiments on organic photoconversion systems show that excessive excitation energy in such systems is not lost but used to reach delocalised states that act as the gateway for long-range charge separation. We also show that the developed experimental approach can be generalised to inorganic and hybrid photoconversion systems.

Arginase is a multifaced enzyme that plays an important role in health and disease being regarded as a therapeutic target for the treatment of various pathological states such as malignancies, asthma, and cardiovascular disease. The discovery of boronic acid-based arginase inhibitors in 1997 revolutionized attempts of medicinal chemistry focused on development of drugs targeting arginase. Unfortunately, these very polar compounds had limitations such as analysis and purification without chromophores, synthetically challenging space, and poor oral bioavailability. Herein, we present a novel class of boronic acid-based arginase inhibitors which are piperidine derivatives exhibiting a different pharmacological profile compared to our drug candidate in cancer immunotherapy -OATD-02 - dual ARG1/2 inhibitor with high intracellular activity. Compounds from this new series show low intracellular activity, hence they can inhibit mainly extracellular arginase, providing different therapeutic space compared to a dual intracellular ARG1/2 inhibitor. The disclosed series showed good inhibitory potential towards arginase enzyme in vitro (IC 50 up to 160 nM), favorable pharmacokinetics in animal models, and encouraging preliminary in vitro and in vivo tolerability. Compounds from the new series have moderate-to-high oral bioavailability (up to 66 %) and moderate clearance in vivo. Herein we describe the development and optimization of the synthesis of the new class of boronic acid-based arginase inhibitors via a ring expansion approach starting from the inexpensive chirality source (d-hydroxyproline). This upgraded methodology facilitated a gram-scale delivery of the final compound and eliminated the need for costly and time-consuming chiral resolution., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Roman Blaszczyk reports financial support was provided by Molecure S.A. Roman Blaszczyk reports a relationship with Molecure S.A. that includes: employment and equity or stocks. Roman Blaszczyk has patent #Dipeptide piperidine derivatives (US10851099B2) issued to Molecure S.A. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

The initial aim of this work was to elucidate the mutual influence of different single-stranded segments (loops and caps) on the thermodynamic stability of RNA G-quadruplexes. To this end, we used a new NAB-GQ-builder software program, to construct dozens of two-tetrad G-quadruplex topologies, based on a designed library of sequences. Then, to probe the sequence-morphology-stability relationships of the designed topologies, we performed molecular dynamics simulations. Their results provide guidance for the design of G-quadruplexes with balanced structures, and in turn programmable physicochemical properties for applications as biomaterials. Moreover, by comparative examinations of the single-stranded segments of three oncogene promoter G-quadruplexes, we assess their druggability potential for future therapeutic strategies. Finally, on the basis of a thorough analysis at the quantum mechanical level of theory on a series of guanine assemblies, we demonstrate how a valence tautomerism, triggered by a coordination of cations, initiates the process of G-quadruplex folding, and we propose a sequential folding mechanism, otherwise dictated by the cancellation of the dipole moments on guanines.

The receptor for advanced glycation end products (RAGE) is an immunoglobulin-type multiligand transmembrane protein expressed in numerous cell types, including the central nervous system cells. RAGE interaction with S100B, released during brain tissue damage, leads to RAGE upregulation and initialization of a spiral proinflammatory associated with different neural disorders. Here, we present the structural characterization of the hetero-oligomeric complex of the full-length RAGE with S100B, obtained by a combination of mass spectrometry-based methods and molecular modeling. We predict that RAGE functions as a tightly packed tetramer exposing a positively charged surface formed by V domains for S100B binding. Based on HDX results we demonstrate an allosteric coupling of the distal extracellular V domains and the transmembrane region, indicating a possible mechanism of signal transmission by RAGE across the membrane. Our model provides an insight into RAGE-ligand interactions, providing a basis for the rational design of the therapeutic modifiers of its activity., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

RNA has been found to play an ever-increasing role in a variety of biological processes. The function of most non-coding RNA molecules depends on their structure. Comparing and classifying macromolecular 3D structures is of crucial importance for structure-based function inference and it is used in the characterization of functional motifs and in structure prediction by comparative modeling. However, compared to the numerous methods for protein structure superposition, there are few tools dedicated to the superimposing of RNA 3D structures. Here, we present SupeRNAlign (v1.3.1), a new method for flexible superposition of RNA 3D structures, and SupeRNAlign-Coffee-a workflow that combines SupeRNAlign with T-Coffee for inferring structure-based sequence alignments. The methods have been benchmarked with eight other methods for RNA structural superposition and alignment. The benchmark included 151 structures from 32 RNA families (with a total of 1734 pairwise superpositions). The accuracy of superpositions was assessed by comparing structure-based sequence alignments to the reference alignments from the Rfam database. SupeRNAlign and SupeRNAlign-Coffee achieved significantly higher scores than most of the benchmarked methods: SupeRNAlign generated the most accurate sequence alignments among the structure superposition methods, and SupeRNAlign-Coffee performed best among the sequence alignment methods., (© The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.)

We present a multi-scale model for charge transport across grain boundaries in molecular electronic materials that incorporates packing disorder, electrostatic and polarisation effects. We choose quasi two-dimensional films of tri-isopropylsilylethynyl pentacene (TIPS-P) as a model system representative of technologically relevant crystalline organic semiconductors. We use atomistic molecular dynamics, with a force-field specific for TIPS-P, to generate and equilibrate polycrystalline two-dimensional thin films. The energy landscape is obtained by calculating contributions from electrostatic interactions and polarization. The variation in these contributions leads to energetic barriers between grains. Subsequently, charge transport is simulated using a kinetic Monte-Carlo algorithm. Two-grain systems with varied mutual orientation are studied. We find relatively little effect of long grain boundaries due to the presence of low impedance pathways. However, effects could be more pronounced for systems with limited inter-grain contact areas. Furthermore, we present a lattice model to generalize the model for small molecular systems. In the general case, depending on molecular architecture and packing, grain boundaries can result in interfacial energy barriers, traps or a combination of both with qualitatively different effects on charge transport.

The recently synthesized series of Pt(II) complexes containing cyclometallating (phenylpyridine or benzoquinoline) and N-heterocyclic carbene ligands possess intriguing structures, topologies, and light emitting properties. Here, we report curious physicochemical interactions between in situ PVD-grown films of a typical representative of the aforementioned Pt(II) complex compounds and Li, Na, K and Cs atoms. Based on a combination of detailed core-level photoelectron spectroscopy and quantum-chemical calculations at the density functional theory level, we found that the deposition of alkali atoms onto the molecular film leads to unusual redistribution of electron density: essential modification of nitrogen sites, reduction of the coordination Pt(II) centre to Pt(0) and decrease of electron density on the bromine atoms. A possible explanation for this is formation of a supramolecular system "Pt complex-alkali metal ion"; the latter is supported by restoration of the system to the initial state upon subsequent oxygen treatment. The discovered properties highlight a considerable potential of the Pt(II) complexes for a variety of biomedical, sensing, chemical, and electronic applications.

The generation, under self-assembly conditions, of coordination polymers on surface based combinations of a terpyridine-antracene-pyridine based tecton and Co(II) or Pd(II) cations is primarily governed by the coordination geometry of the metal center (octahedral and square planar respectively). While the octahedral Co(II) based polymer self-assembles in insulating films exhibiting randomly oriented crystalline domains, the planarity of Pd(II) based polymers leads to the formation of conductive π-π stacked fibrillar structures exhibiting anisotropically oriented domains. In the latter case, the favorable Pd-Pd and anthracene-anthracene wavefunction overlaps along the fiber direction are responsible for the large electronic couplings between adjacent chains, whereas small electronic couplings are instead found along individual polymer chains. These results provide important guidelines for the design of conductive metal coordination polymers, highlighting the fundamental role of both intra- as well as inter-chain interactions, thus opening up new perspectives towards their application in functional devices.

Electron spin is a key consideration for the function of organic semiconductors in light-emitting diodes and solar cells, as well as spintronic applications relying on organic magnetoresistance. A mechanism for triplet excited state generation in such systems is by recombination of electron-hole pairs. However, the exact charge recombination mechanism, whether geminate or nongeminate and whether it involves spin-state mixing is not well understood. In this work, the dynamics of free charge separation competing with recombination to polymer triplet states is studied in two closely related polymer-fullerene blends with differing polymer fluorination and photovoltaic performance. Using time-resolved laser spectroscopic techniques and quantum chemical calculations, we show that lower charge separation in the fluorinated system is associated with the formation of bound electron-hole pairs, which undergo spin-state mixing on the nanosecond timescale and subsequent geminate recombination to triplet excitons. We find that these bound electron-hole pairs can be dissociated by electric fields.

The structural organization of three different families of semicrystalline π-conjugated polymers is reported (poly(3-hexylthiophene) (P3HT), poly[2,6-(4,4-bis-alkyl-4H-cyclopenta-[2,1-b;3,4-b0]-dithiophene)-alt-4,7-(2,1,3-benzothiadiazole)](cyclopentadithiophene-benzothiadiazole) (CDT-BTZ) and poly(N,N"-bis-2-octyldodecylnaphtalene-1,4,5,8-bis-dicarboximide-2,6-diyl-alt-5,5-2,2-bithiophene (P(NDI2OD-T2))). These have triggered significant interest for their remarkable charge-transport properties. By performing molecular mechanics/dynamics simulations with carefully re-parameterized force fields, it is illustrated in particular how the supramolecular organization of these conjugated polymers is driven by an interplay between the length and nature of the conjugated monomer unit and the packing of their alkyl side chains, and to what extent it impacts the charge-carrier mobility, as monitored by quantum-chemical calculations of the intermolecular hopping transfer integrals. This Progress Report is concluded by providing generic guidelines for the design of materials with enhanced degrees of supramolecular organization., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

While highly desired in integrated optical circuits, multiresponsive and tunable nonlinear optical (NLO) active 1D (sub)wavelength scale superstructures from organic materials are rarely reported due to the strong tendency of organic molecules to self-assembly in centrosymmetric modes. Here a solution-processed assembly approach is reported to generate non-centrosymmetric single-crystalline organic microfibers with a cumulative dipole moment for anisotropic combined second- and third-order NLO., (Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Molecular modeling shows that longitudinal displacement of the backbones by a couple of ångströms has a profound impact on the electronic coupling mediating charge transport in a conjugated copolymer. These changes can be probed by monitoring the calculated X-ray scattering patterns and NMR chemical shifts as a function of sliding of the polymer chains and comparing them to experiment., (Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

We report the electronic properties of the conjugated coupling between a donor polymer and an acceptor segment serving as a model for the coupling in conjugated donor-acceptor block copolymers. These structures allow the study of possible intrachain photoinduced charge separation, in contrast to the interchain separation achieved in conventional donor-acceptor blends. Depending on the nature of the conjugated linkage, we observe varying degrees of modification of the excited states, including the formation of intrachain charge transfer excitons. The polymers comprise a block (typically 18 repeat units) of P3HT, poly(3-hexyl thiophene), coupled to a single unit of F8-TBT (where F8 is dioctylfluorene, and TBT is thiophene-benzothiadiazole-thiophene). When the P3HT chain is linked to the TBT unit, we observe formation of a localized charge transfer state, with red-shifted absorption and emission. Independent of the excitation energy, this state is formed very rapidly (<40 fs) and efficiently. Because there is only a single TBT unit present, there is little scope for long-range charge separation and it is relatively short-lived, <1 ns. In contrast, when the P3HT chain and TBT unit are separated by the wider bandgap F8 unit, there is little indication for modification of either ground or excited electronic states, and longer-lived charge separated states are observed.

The electron-hole pair created via photon absorption in organic photoconversion systems must overcome the Coulomb attraction to achieve long-range charge separation. We show that this process is facilitated through the formation of excited, delocalized band states. In our experiments on organic photovoltaic cells, these states were accessed for a short time (<1 picosecond) via infrared (IR) optical excitation of electron-hole pairs bound at the heterojunction. Atomistic modeling showed that the IR photons promote bound charge pairs to delocalized band states, similar to those formed just after singlet exciton dissociation, which indicates that such states act as the gateway for charge separation. Our results suggest that charge separation in efficient organic photoconversion systems occurs through hot-state charge delocalization rather than energy-gradient-driven intermolecular hopping.