The use of residual dipolar coupling for conformational analysis of structurally related natural products

The authors would like to acknowledge the EPSRC for funding.Determining the conformational preferences of molecules in solution remains a considerable challenge. Recently, the use of residual dipolar coupling (RDC) analysis has emerged as a key method to address this. Whilst to date the majority of the applications have focused on biomolecules including proteins and DNA, the use of RDCs for studying small molecules is gaining popularity. Having said that, the method continues to develop and here we describe an early case study of the quantification of conformer populations in small molecules using RDC analysis. Having been inspired to study conformational preferences by unexpected differences in the NMR spectra and the reactivity of related natural products, we showed that the use of more established techniques was unsatisfactory in explaining the experimental observations. The use of RDCs provided an improved understanding which, following use of methods to quantify conformer populations using RDCs, culminated in a rationalisation of the contrasting diastereoselectivities observed in a ketone reduction reactionPostprintPeer reviewe

Cooperative binding in a phosphine oxide-based halogen bonded dimer drives supramolecular oligomerization

The authors thank the Marie Curie Initial Training Network on Replication and Adaption in Networks (ReAd) for financial support (early stage researcher funding to L.M.).Triphenylphosphine oxide forms halogen-bonded (XB) complexes with pentafluoroiodobenzene and a 1,4-diaryl-5-iodotriazole. The stability of these complexes is assessed computationally and by 31P NMR spectroscopy in d8-toluene solution, where both complexes are weakly associated. This knowledge is applied to the design and synthesis of two self-complementary phosphine oxide-iodotriazole hybrids that incorporate a phosphine oxide XB acceptor and a 1,4-diphenyl-5-iodotriazole XB donor within the same molecule. The self-complementary design of these modules facilitates their assembly in both d8-toluene and, surprisingly, d2-DCM into dimers, with significant stabilities, through the formation of halogen-bonded diads. The stability of these assemblies is a result of significant levels of cooperative binding that is present in both solvents. The connection of two of these hybrid units together, using a flexible spacer, facilitates the aggregation of these modules in d2-DCM solution, through halogen bonding, forming oligomeric assemblies.PostprintPeer reviewe

Integration of an active research data system with a data repository to streamline the research data lifecycle : Pure-NOMAD case study

The authors acknowledge the work of Juan Karsten for the partial development of the Pure-NOMAD integration. This work has been supported by the EPSRC-Strategic Partners Project (2012, grant number EP/J501542/1) and the Impact Acceleration Account (2016, grant number EP/K503940/1).Research funders have introduced requirements that expect researchers to properly manage and publicly share their research data, and expect institutions to put in place services to support researchers in meeting these requirements. So far the general focus of these services and systems has been on addressing the final stages of the research data lifecycle (archive, share and re-use), rather than stages related to the active phase of the cycle (collect/create and analyse). As a result, full integration of active data management systems with data repositories is not yet the norm, making the streamlined transition of data from an active to a published and archived status an important challenge. In this paper we present the integration between an active data management system developed in-house (NOMAD) and Elsevier’s Pure data repository used at our institution with the aim of offering a simple workflow to facilitate and promote the data deposit process. The integration results in a new data management and publication workflow that helps researchers to save time, minimize human errors related to manually handling files, and further promote data deposit together with collaboration across the institution.PostprintPeer reviewe

Synthesis and conformational analysis of fluorinated uridine analogues provide insight into a neighbouring-group participation mechanism

Funding: This work was supported by the EPSRC council (Grant number 1398501) and GlaxoSmithKline.Fluorinated nucleoside analogues have attracted much attention as anticancer and antiviral agents and as probes for enzymatic function. However, the lack of direct synthetic methods, especially for 2′,3′-dideoxy-2′,3′-difluoro nucleosides, hamper their practical utility. In order to design more efficient synthetic methods, a better understanding of the conformation and mechanism of formation of these molecules is important. Herein, we report the synthesis and conformational analysis of a 2′,3′-dideoxy-2′,3′-difluoro and a 2′-deoxy-2′-fluoro uridine derivative and provide an insight into the reaction mechanism. We suggest that the transformation most likely diverges from the SN1 or SN2 pathway, but instead operates via a neighbouring-group participation mechanism.Publisher PDFPeer reviewe

Fluorine induced pseudo-anomeric effects in methoxycyclohexanes through electrostatic 1,3-diaxial interactions

Authors thank FAPESP, CONFAP and The UK Academies for a São Paulo International Research Collaboration (FAPESP #2019/05028-7). FAPESP is also gratefully acknowledge for an undergraduate fellowship to BAP (#2019/03855-3), and a Young Research Award to RAC (#2018/03910-1). The Chinese Scholarship Council (CSC) is thanked for a Studentship (CY). Finally CENAPAD-SP, CESUP and SDumont are acknowledged for computational resources used in theory calculations.We report counter‐intuitive axial preferences in non‐stereochemically biased, selectively fluorinated methoxycyclohexanes. These pseudo‐anomeric effects are apparent when electronegative CF2 groups are placed at the C‐2, C‐4 and C‐6 positions of the cyclohexane ring to render the C‐3/5 axial hydrogen atoms electropositive. The electrostatic interaction between these axial hydrogen atoms and the ‐OMe oxygen is stabilising. The effect is explored using high‐level ab initio and DFT calculations in the framework of NBO, QTAIM and NCI analysis across a range of derivatives, and experimentally (19F{1H}‐NMR at −80 °C) for some illustrative examples. The effect is significant in energy terms for a weak interaction, and illustrates a new stereoelectronic aspect attributed to selective fluorine substitution in organic chemistry.Publisher PDFPeer reviewe

Catalytic Activity and Fluxional Behavior of Complexes Based on RuHCl(CO)(PPh₃)₃ and Xantphos-Type Ligands

With RuHCl(CO)(PPh3)3 as the starting material, the complexes RuHCl(CO)(PPh3)(L) were prepared for L = Xantphos and closely related ligands. Their catalytic activity in the direct amination of cyclohexanol showed large differences depending on the different backbone structures. In those complexes the Xantphos-type ligand backbones are slightly bent and display fluxionality, studied by VT-NMR. This was assigned to the "flipping" of the backbone via the bridging atoms in the xanthene backbone. Via line shape analysis of the peaks, the Gibbs free energy of activation of the flipping movement was found to be around 56 kJ/mol in all cases. However, the activation enthalpy and entropy differed considerably. Employing RuCl2(PPh3)3 as the precursor resulted in the trans-coordinated complexes RuCl2(PPh3)(L) for L = Xantphos, Sixantphos. Fluxionality was no longer observed, due to the fact that in these complexes the O atom in the backbone also coordinates to the Ru

Synthesis of indoloquinolines : an intramolecular cyclization leading to advanced Perophoramidine-relevant intermediates

We thank EPSRC (UK) for a DTA studentship for C.A.J.The bioactive natural product perophoramidine has proved a challenging synthetic target. An alternative route to its indolo[2,3-b]quinolone core structure involving an N-chlorosuccinimde mediated intramolecular cylization reaction is reported. Attempts to progress towards the natural product are also discussed with an unexpected deep-seated rearrangement of the core structure occurring during an attempted iodoetherification reaction. X-ray crystallographic analysis provides important analytical confirmation of assigned structures.Publisher PDFPeer reviewe

Using fractionation and diffusion ordered spectroscopy to study lignin molecular weight

This work was supported by EPSRC Ph.D. studentships EP/1654168 (JRDM). EP/1654168/1. Raw data files can be found at: https://doi.org/10.6084/m9.figshare.8034680Recent reports demonstrate that applications of the biopolymer lignin can be helped by the use of a portion of the lignin which has an optimal molecular weight range. Unfortunately, the current methods used to determine lignin’s molecular weight are inconsistent or not widely accessible. Here, an approach that relies on 2D DOSY NMR analysis is described that provides a measure of lignin’s molecular weight. Consistent results were obtained using this well-established NMR technique across a range of lignins.Publisher PDFPeer reviewe

Ligand hydrogenation during hydroformylation catalysis detected by in-situ high-pressure infra-red spectroscopic analysis of a rhodium/phospholene-phosphite catalyst

Phospholane-phosphites are known to give highly unusual selectivity’s towards branched aldehydes in the hydroformylation of terminal alkenes. This paper describes the synthesis of hitherto unknown unsaturated phospholene-borane precursors and their conversion to the corresponding phospholene-phosphites. The relative stereochemistry of one of these ligands, and it’s Pd complex was assigned with the aid of X-ray crystal structure determinations. These ligands were able to approach the level of selectivity observed for phospholane-phosphites in the rhodium catalysed hydroformylation of propene. High-Pressure-Infra-Red (HPIR) spectroscopic monitoring of the catalyst formation revealed that whilst the catalysts show good thermal stability with respect to fragmentation, the C=C bond in the phospholene is slowly hydrogenated in the presence of rhodium and syngas. The ability of this spectroscopic tool to detect even subtle changes in structure, remote from the carbonyl ligands underlines the usefulness of HPIR spectroscopy in hydroformylation catalyst development.Peer reviewe

Adolescents and the Media: Trust with Reservations?

Neprestani razvoj tehnologije čini današnjem čovjeku dostupnim sve veći broji informacija. Sadržaji tih informacija predstavljaju i različite stavove, koji proizlaze iz različitih vrijednosnih okvira te nerijetko jedni druge dovode u pitanje. U interpretaciji medijskih poruka primatelj nije nužno prepušten samome sebi. To su potvrdila istraživanja još četrdesetih godina prošlog stoljeća, uočavajući protok informacija na dvije razine (Two Step Flow of Communication), gdje su identificirani tzv. opinion leaders kao posrednici između sadržaja poruke i primatelja, koje se drži vjerodostojnim u interpretaciji poruke. Zanima nas na koji način adolescenti, koji su u razdoblju života kad preispituju svoje stavove i uvjerenja, primaju medijske poruke koje mogu biti i međusobno kontradiktorne. Donosimo rezultate istraživanja provedenog 2010. godine na području Varaždinske biskupije. U istraživanju o utjecaju sredstava komunikacije na religiozni identitet adolescenata obrađuju se i pitanja vezana za povjerenje srednjoškolaca u medijske sadržaje. Rezultati istraživanja pokazuju da većina ispitanika tvrdi kako neće usvojiti medijske sadržaje koji se ne slažu s njihovim postojećim stavovima i uvjerenjima a da ih prethodno ne provjere. Prema odgovorima ispitanika, za provjeru primljenih informacija obratit će se osobama iz njihova fizičkog ambijenta, ali još više od toga koristit će medije kao kanale za provjeru tih informacija. Tu im je internet napose važan izvor o sadržajima i pitanjima koja se ne usude postaviti u interpersonalnoj komunikaciji.With constant technological development an increasing number of pieces of information is available to the contemporary human being. The contents of these pieces of information represent different attitudes, which arise from different value frameworks and frequently challenge each other. In the interpretation of media messages, the receiver is not necessarily left to himself. This was also confirmed in the studies in the 1940ies, which noticed Two Step Flow of Communication, where opinion leaders were identified as mediators between the message contents and receivers and who were considered trustworthy in the interpretation of the message. We are interested in what way adolescents, who are in the period of life when they re-examine their attitudes and beliefs, receive media messages that can be mutually contradictory. We present the results of the research conducted in 2010 in the Roman Catholic Diocese of Varaždin. The research was conducted on the influence of means of communication on religious identity of adolescents, and focuses, among other topics, on the trust of high school students in media contents. Research results show that most respondents claim they will not adopt media contents that disagree with their existing attitudes and beliefs without verifying them first. According to the respondents’ answers they will speak to persons from their physical environment in order to verify received information. Moreover, they will use the media to verify these pieces of information. Therein, the internet is of the utmost importance as the source of contents and issues which they do not dare to ask in interpersonal communication