0000000001299409
AUTHOR
Miguel A. González
Continuous ambulatory peritoneal dialysis as a therapeutic alternative in patients with advanced congestive heart failure.
Aims Continuous ambulatory peritoneal dialysis (CAPD) has been proposed as an additional therapeutic resource for patients with advanced congestive heart failure (CHF). The objective of this study was to determine the therapeutic role of CAPD, in terms of surrogate endpoints, in the management of patients with advanced CHF and renal dysfunction. A total of 57 candidates with New York Heart Association (NYHA) class III/IV CHF, renal dysfunction (glomerular filtration rate , 60 mL/min/1.73 m 2 ), persistent fluid congestion despite loop diuretic treatment, and at least two previous hospitalizations for acute heart failure (AHF) were invited to be included in the CAPD programme; however, 25 pa…
Synthesis of spongian diterpenes: (−)-spongian-16-oxo-17-al and (−)-acetyldendrillol-1
Abstract An efficient diastereoselective synthesis of the spongian diterpenes (−)-spongian-16-oxo-17-al ( 1 ) and (−)-acetyldendrillol-1 ( 13 ) is described starting from (+)-podocarp-8(14)-13-one ( 6 ) via the ester-dialdehyde 11 as key intermediate. The absolute configuration at C-17 in synthetic compound 13 has conclusively been proved by NOE experiments.
Anti-herpetic and anti-dengue activity of abietane ferruginol analogues synthesized from (+)-dehydroabietylamine
The abietane-type diterpenoid (+)-ferruginol (1), a bioactive compound isolated from several plants, has attracted much attention as consequence of its pharmacological properties, which includes antibacterial, antifungal, antimicrobial, cardioprotective, anti-oxidative, anti-plasmodial, leishmanicidal, anti-ulcerogenic, anti-inflammatory and antitumor actions. In this study, we report on the antiviral evaluation of ferruginol (1) and several analogues synthesized from commercial (+)-dehydroabietylamine. Thus, the activity against Human Herpesvirus type 1, Human Herpesvirus type 2 and Dengue Virus type 2, was studied. Two ferruginol analogues showed high antiviral selectivity index and reduc…
Diálisis peritoneal en pericarditis constrictiva: a propósito de 3 casos
Prognostic value of NT-proBNP and CA125 across glomerular filtration rate categories in acute heart failure.
This study aimed to evaluate whether glomerular filtration rate (eGFR) during admission modifies the predictive value of plasma amino-terminal pro-brain natriuretic peptide (NT-proBNP) and carbohydrate antigen 125 (CA125) in patients hospitalized for acute heart failure (AHF).We retrospectively evaluated 4595 patients consecutively discharged after admission for AHF at three tertiary-care hospitals from January 2008 through October 2019. To investigate the effect of kidney function on the association of NT-proBNP and CA125 with 1-year mortality (all-cause and cardiovascular mortality), we stratified patients according to four eGFR categories:30 mL•minAt 1-year follow-up, 748 of 4595 (16.3%)…
Synthesis and biological evaluation of pyridinebetaine A and B
The synthesis of the marine natural products pyridinebetaine A and B is reported. The biological evaluation of pyridinebetaine A and B and several analogues as cytotoxic, antifungal and antiviral agents is also described. Unfortunately, none of the compounds tested showed relevant antifungal or cytotoxic activity. Only pyridinebetaine B reduced the Herpes simplex virus type 1 virus replication, though only weakly.
Continuous ambulatory peritoneal dialysis and clinical outcomes in patients with refractory congestive heart failure.
A B S T R A C T Introduction and objectives: Peritoneal dialysis has been proposed as a therapeutic alternative for patients with refractory congestive heart failure. The objective of this study was to assess its effect on long-term clinical outcomes in patients with advanced heart failure and renal dysfunction. Methods: A total of 62 patients with advanced heart failure (class III/IV), renal dysfunction (glomerular filtration<60 mL/min/1.73 m 2 ), persistent fluid congestion despite loop diuretic treatment and at least 2 previous hospitalizations for heart failure were invited to participate in a continuous ambulatory peritoneal dialysis program. Of these, 34 patients were excluded and adj…
Antimalarial activity of abietane ferruginol analogues possessing a phthalimide group.
The abietane-type diterpenoid (+)-ferruginol, a bioactive compound isolated from New Zealand’s Miro tree (Podocarpus ferruginea), displays relevant pharmacological properties, including antimicrobial, cardioprotective, anti-oxidative, anti-plasmodial, leishmanicidal, anti-ulcerogenic, anti-inflammatory and anticancer. Herein, we demonstrate that ferruginol (1) and some phthalimide containing analogues 2–12 have potential antimalarial activity. The compounds were evaluated against malaria strains 3D7 and K1, and cytotoxicity was measured against a mammalian cell line panel. A promising lead, compound 3, showed potent activity with an EC50 = 86 nM (3D7 strain), 201 nM (K1 strain) and low cyto…
Synthesis and Biological Evaluation of Combretastatin A-4 and Three Combretastatin-Based Hybrids
The syntheses of combretastatin A-4 from gallic acid and of three combretastatin-based hybrids are described. Starting from commercial gallic acid, the phosphonium salt (3,4,5-trimethoxybenzylphosphonium bromide) is synthesized and coupled, through a Wittig reaction, with several aldehydes, including methoxymethyl-protected isovanillin, the aldehyde γ-bicyclohomofarnesal having a labdane skeleton, 3-(3-pyridyl) propanal, and furfural. The biological properties of the cis-coupled compounds as cytotoxic, antiviral and antifungal agents are also reported. In addition, pyrogallol, gallic and 3,4,5-trimethoxybenzoic acids have been studied biologically.
Synthesis and biological evaluation of (+)-labdadienedial, derivatives and precursors from (+)-sclareolide
Labdadienedial and a series of C15,C16-functionalized derivatives were synthesized from commercial (+)-sclareolide and evaluated for their cytotoxic, antimycotic, and antiviral activities. Their precursors were similarly evaluated.
Assignment of1H and13C NMR data for (−)-methyl thyrsiflorin A and some scopadulan precursors
The 1H and 13C NMR spectral analysis of synthetic (−)-methylthyrsiflorin A and 10 scopadulan precursors is reported. Resonance assignments were based on one- and two-dimensional NMR techniques, which included 1H, 13C, DEPT and HMQC and also 1D NOE difference spectroscopy. Copyright © 2001 John Wiley & Sons, Ltd.
Short syntheses of (+)-ferruginol from (+)-dehydroabietylamine
Short syntheses of bioactive (+)-ferruginol in five or six synthetic steps starting from commercially available (+)-dehydroabietylamine are described. The oxygenated function at C12 was introduced via a Friedel–Crafts acylation of N-phthaloyldehydroabietylamine followed by Baeyer–Villiger oxidation. Then, overall deprotection of functional groups, reductive deamination or biomimetic oxidative deamination, and final Wolff–Kishner reduction provided (+)-ferruginol in 21 and 23% overall yields, respectively.
Bases para la creación de las unidades clínicas cardiorrenales. Documento de consenso de los grupos de trabajo cardiorrenal de la SEC y la SEN
Resumen La enfermedad renal es una de las comorbilidades halladas con mayor frecuencia en los pacientes con insuficiencia cardiaca. Su presencia se asocia a peor pronostico y genera gran incertidumbre sobre la monitorizacion y abordaje terapeutico. De este modo, las unidades cardiorrenales han surgido como elementos integradores, que desde un punto de vista multidisciplinar pretenden vehiculizar la asistencia, docencia e investigacion de este amplio espectro de pacientes. En el presente documento de consenso elaborado por el Grupo de Trabajo de Sindrome Cardiorrenal y Tratamiento de la Congestion en la Insuficiencia Cardiaca de la Sociedad Espanola de Cardiologia y el Grupo de Trabajo de Me…
(+)-Dehydroabietylamine derivatives target triple-negative breast cancer.
Breast cancer remains the leading cause of cancer-related death among women. The invasive triple-negative subtype is unresponsive to estrogen therapy, and few effective treatments are available. In search of new chemical scaffolds to target this disease, we conducted a phenotypic screen against the human breast carcinoma cell lines MDA-MB-231, MA11, and MCF-7 using terrestrial natural products. Natural products that preferentially inhibited proliferation of triple-negative MDA-MB-231 cells over estrogen receptor-positive cells were further studied; herein we focused on the abietanes. The activity of the abietane carnosol prompted us to generate a focus library from the readily available (+)…
A Switchable Molecular Rotator: Neutron Spectroscopy Study on a Polymeric Spin-Crossover Compound
A quasielastic neutron scattering and solid-state 2H NMR spectroscopy study of the polymeric spin-crossover compound {Fe(pyrazine)[Pt(CN) 4]} shows that the switching of the rotation of a molecular fragment-the pyrazine ligand-occurs in association with the change of spin state. The rotation switching was examined on a wide time scale (10 -13-10 -3 s) by both techniques, which clearly demonstrated the combination between molecular rotation and spin-crossover transition under external stimuli (temperature and chemical). The pyrazine rings are seen to perform a 4-fold jump motion about the coordinating nitrogen axis in the high-spin state. In the low-spin state, however, the motion is suppres…
1H and13C NMR assignments and conformational analysis of some podocarpene derivatives
This paper reports on the assignment of the 1 Ha nd 13 C NMR spectra of five podocarpene derivatives. Resonance assignments were made on the basis of one- and two-dimensional NMR techniques which included 1 H, 13 C, DEPT and HMQC and also 1D NOE difference spectroscopy. The ratio of the different conformers in the six- membered C-ring of the podocarpene system was determined by molecular mechanics calculations and analysis of proton spin-spin coupling constants. Copyright © 2000 John Wiley & Sons, Ltd.
CA125 but not NT-proBNP predicts the presence of a congestive intrarenal venous flow in patients with acute heart failure
Abstract Background Intrarenal venous flow (IRVF) measured by Doppler ultrasound has gained interest as a potential surrogate marker of renal congestion and adverse outcomes in heart failure. In this work, we aimed to determine if antigen carbohydrate 125 (CA125) and plasma amino-terminal pro-B-type natriuretic peptide (NT-proBNP) are associated with congestive IRVF patterns (i.e., biphasic and monophasic) in acute heart failure (AHF). Methods and results We prospectively enrolled a consecutive cohort of 70 patients hospitalized for AHF. Renal Doppler ultrasound was assessed within the first 24-h of hospital admission. The mean age of the sample was 73.5 ± 12.3 years; 47.1% were female, and…
Diálisis peritoneal ambulatoria continua y evolución clínica de pacientes con insuficiencia cardiaca congestiva refractaria
Introduccion y objetivos Se ha propuesto el empleo de la dialisis peritoneal como alternativa para los pacientes con insuficiencia cardiaca congestiva refractaria. El objetivo de este estudio es evaluar su efecto en la evolucion clinica a largo plazo de los pacientes con insuficiencia cardiaca avanzada y disfuncion renal. Metodos Se invito a un total de 62 pacientes, con insuficiencia cardiaca avanzada (clase III/IV), disfuncion renal (filtrado glomerular < 60ml/min/1,73 m2), congestion persistente por exceso de liquidos a pesar del tratamiento con diureticos de asa y al menos dos hospitalizaciones previas por insuficiencia cardiaca, a participar en un programa de dialisis peritoneal ambula…
Refractory congestive heart failure: when the solution is outside the heart
Abstract Refractory congestive heart failure is associated with an ominous prognosis in which the treatments strategies remain scarce and not well validated. In the last years, continuous ambulatory peritoneal dialysis (CAPD) has emerged as a therapeutic alternative in this subset of patients. So far, it has been associated with a significant improvement in functional capacity and quality of life, together with a striking reduction in the risk of readmissions. We present the case of an elderly patient with severe left ventricular dysfunction and severe mitral and tricuspid regurgitation who presents recurrent admissions for anasarca. After its inclusion in a CAPD programme, the patient expe…
Synthesis and antiviral activity of scopadulane-rearranged diterpenes.
A new bioactive diterpene skeleton resulting from a backbone rearrangement is described. Activity of the rearranged product and several derivatives against Herpes Virus Simplex type 2 is reported.
Synthesis of C-17-functionalized spongiane diterpenes: diastereoselective synthesis of (-)-spongian-16-oxo-17-al, (-)-acetyldendrillol-1, and (-)-aplyroseol-14.
The diastereoselective synthesis of spongiane diterpenes (-)-spongian-16-oxo-17-al 2, (-)-acetyldendrillol-1 15, and (-)-aplyroseol-14 16 has been completed efficiently via the common intermediate 14. Compound 14 was prepared in five synthetic steps from (+)-podocarp-8(14)-en-13-one 13, easily available from commercial (-)-abietic acid. The key steps in the syntheses were a regioselective reduction of a 1,4-dialdehyde unit, a one-pot acetalization-acetylation, and a translactonization. The synthesis of 15 and 16 has led us to a revision of the configuration at C-17 for natural (-)-acetyldendrillol-1 and a structural reassignment for aplyroseol-14. Thus, aplyroseol-14 16 presents an unpreced…
Synthesis and antiviral activity of scopadulcic acids analogues
The synthesis and antiviral properties of several scopadulcic acid analogues functionalized at C-6/C-7 and C-13 is reported. The preparation of advanced intermediates for the synthesis of scopadulcic acid B/scopadulciol analogues is also described. The biological study revealed the importance of polar groups at C-13, while the stereochemistry at C-8 was not critical for activity.
(-)-(5S,8S,9R,10S,13R,14R)-15,16-Dideoxy-16,17-epoxy-16-oxospongian-15-yl acetate.
The title compound (aplyroseol-14), C22H34O4, exhibits a lactone-based structure that is novel for spongian-type diterpenoids. The structure, which features a six-membered lactone ring, was proposed by Arno, Gonzalez & Zaragoza [J. Org. Chem. (2003), 68, 1242–1251] on the basis of spectroscopic data and chemical correlations. This assignment has been confirmed, and it is shown that the molecule contains a trans–anti–trans 6/6/6 tricyclic hydrocarbon system and that the acetoxymethyl group lies in an equatorial position. Pairs of near-linear C—H⋯O interactions link molecules into extended chains.
Synthesis and biological evaluation of abietic acid derivatives
A series of C18-oxygenated derivatives of abietic acid were synthesized and evaluated for their cytotoxic, antimycotic, and antiviral activities. In general, the introduction of an aldehyde group at C18 did improve the resultant bioactivity, while the presence of an acid or alcohol led to less active compounds.
Peritoneal Dialysis in Constrictive Pericarditis: A Report of Three Cases
1H and 13C NMR signal assignment of synthetic (-)-methyl thyrsiflorin B acetate, (-)-thyrsiflorin C and several scopadulane derivatives.
The 1H and 13C NMR signal assignment of the data of 13 scopadulane-type diterpenes is reported. It was based on one- and two- dimensional NMR techniques which included 1H, 13C, DEPT, HMQC and 1D NOE difference spectroscopy. Copyright © 2005 John Wiley & Sons, Ltd.
Attempted synthesis of spongidines by a radical cascade terminating onto a pyridine ring.
Mn(III)-based oxidative free-radical cyclization of an unsaturated beta-keto ester containing a pyridine ring as radical trap has been studied. This intramolecular reaction of nucleophilic carbon-centered radicals with the pyridine ring leads to the stereospecific construction of a tetracyclic compound in which five chiral centers are created in one pot. This synthetic approach represents the first attempt to prepare the anti-inflammatory pyridinium alkaloids spongidine A, B, and D.
Continuous ambulatory peritoneal dialysis as a promising therapy for light chain amyloidosis with congestive heart failure
Semisynthesis of the Antiviral Abietane Diterpenoid Jiadifenoic Acid C from Callitrisic Acid (4-Epidehydroabietic Acid) Isolated from Sandarac Resin
The semisynthesis of the antiviral abietane diterpenoid (+)-jiadifenoic acid C starting from the available methyl ester of callitrisic acid (4-epidehydroabietic acid) isolated from sandarac resin is reported. A protocol for the isolation of methyl callitrisate (methyl 4-epidehydroabietate) in gram quantities from sandarac resin is also described. Allylic C-17 oxygenation was introduced by regioselective dehydrogenation of the isopropyl group of methyl callitrisate with DDQ followed by selenium-catalyzed allylic oxidation. Ester hydrolysis afforded (+)-jiadifenoic acid C in 22% overall yield from methyl callitrisate. This semisynthetic route provides a convenient source of this anti-Coxsacki…
First Diastereoselective Synthesis of (−)-Methyl Thyrsiflorin A, (−)-Methyl Thyrsiflorin B Acetate, and (−)-Thyrsiflorin C
An efficient procedure for the synthesis of scopadulan diterpenes, using (+)-podocarp-8(14)-en-13-one 13 as starting material, is reported. This procedure has been used for the diastereoselective synthesis of (-)-methyl thyrsiflorin A (8), (-)-methyl thyrsiflorin B acetate (9), and (-)-thyrsiflorin C (7). Key steps in our strategy are the intramolecular cyclopropanation of diazoketone 19 and the regioselective cleavage of the cyclopropane ring.
Synthesis and biological evaluation of dehydroabietic acid derivatives.
A series of C18-oxygenated derivatives of dehydroabietic acid were synthesized from commercial abietic acid and evaluated for their cytotoxic, antimycotic, and antiviral activities.
Synthesis and cytotoxic activity of novel C7-functionalized spongiane diterpenes.
Based on two lead cytotoxic spongiane diterpenes, a new series of C7-oxygenated derivatives were synthesized and evaluated for their antitumor activity in vitro against the cancer cell lines HeLa and HEp-2. In general, introduction of either hydroxyl or acetoxy groups at C-7 did not improve the resultant cytotoxicity, while the presence of a butyrate ester led to more active compounds (CC(50)=4.0-9.5 microM).
SP404OXIDATIVE STRESS AND CHRONIC KIDNEY DISEASE: TRAVELLING COMPANIONS
Determination of the absolute configuration of (−)-abietic acidviaits (4R,5R,9R,10R)-7,13-abietadien-18-ylp-bromobenzoate derivative
The absolute configuration of the title bromo derivative of abietic acid, C27H35BrO2, has been determined. The structural analysis confirms the absolute stereochemistry for (−)-abietic acid proposed by Bose & Struck [(1959). Chem. Ind. (London), pp. 1628–1630] on the basis of optical rotatory dispersion measurements. The molecule exhibits a trans anti 6/6/6 tricyclic hydrocarbon skeleton, with the cyclohexane ring in the expected chair form and the two cyclohexene rings, the double bonds of which are conjugated, in half-chair conformations.
Experimental and DFT study of the conversion of ephedrine derivatives into oxazolidinones. Double SN2 mechanism against SN1 mechanism
Sulfonation of the N-Boc derivatives of 1,2-aminoalcohols, such as ephedrine, pseudoephedrine, norephedrine, norpseudoephedrine, thiomicamine, and chloramphenicol yields a mixture of the corresponding oxazolidinones with inversion (erythro derivatives) and/or retention of configuration (threo derivatives)at C5. We suggest a competition between two mechanisms: an intramolecular SN2 process initiated by attack of the carbonyl oxygen of the Boc group to the benzylic carbon and the other one through a double SN2 process. In the erythro derivatives the first mechanism is predominant, while in the threo derivatives both mechanisms have similar energy. This hypothesis is supported by theoretical c…
Cytotoxic, immunomodulatory, antimycotic, and antiviral activities of semisynthetic 14-hydroxyabietane derivatives and triptoquinone C-4 epimers
A series of C14-hydroxy derivatives of dehydroabietic acid were synthesised from commercial abietic acid and evaluated for their cytotoxic, antimycotic, and antiviral activities. From these C14-hydroxy derivatives, triptoquinone C-4 epimers were obtained and their immunomodulatory activity was additionally evaluated. None of the tested compounds showed antiviral activity against herpes simplex virus type 1 (HHV-1), and nor did they display antimycotic activity against certain Aspergillus, spp. except for one compound, abieta-8,11,13-trien-14,18-diol. Interestingly, two triptoquinone epimers showed cytotoxic activity, and one of them induced mitochondrial potential loss, DNA damage and cell …
Antigen carbohydrate 125 in heart failure: Not just a surrogate for serosal effusions?
Wehave readwith interest the letter CA-125andheart failure:Deja vu or “still to be seen” by Topatan B and Basaran A [1] where the authors concisely reviewed the current pathophysiological knowledgeof CA125 in heart failure (HF). As discussed by these authors, the pathogenesis of this biomarker's elevation inHF is complex andmultifactorial,with apparently different driven forces. For instances, a proinflammatory stimulus (IL-1, tumour necrosis factor-α, lipopolysaccharide) and mesothelial-induced stress appear thekeymechanisms related to the increaseof this biomarker in HF [1–5]. However, no clear evidence exists in regard to how these two mechanisms differentially participate in CA-125 elev…
CCDC 1473649: Experimental Crystal Structure Determination
Related Article: Mónica Giménez-Marqués, Néstor Calvo Galve, Miguel Palomino, Susana Valencia, Fernando Rey, Germán Sastre, Iñigo J. Vitórica-Yrezábal, Mónica Jiménez-Ruiz, J. Alberto Rodríguez-Velamazán, Miguel A. González, José L. Jordá, Eugenio Coronado, Guillermo Mínguez Espallargas|2017|Chemical Science|8|3109|doi:10.1039/C6SC05122G
CCDC 1473650: Experimental Crystal Structure Determination
Related Article: Mónica Giménez-Marqués, Néstor Calvo Galve, Miguel Palomino, Susana Valencia, Fernando Rey, Germán Sastre, Iñigo J. Vitórica-Yrezábal, Mónica Jiménez-Ruiz, J. Alberto Rodríguez-Velamazán, Miguel A. González, José L. Jordá, Eugenio Coronado, Guillermo Mínguez Espallargas|2017|Chemical Science|8|3109|doi:10.1039/C6SC05122G
CCDC 1439097: Experimental Crystal Structure Determination
Related Article: Mónica Giménez-Marqués, Néstor Calvo Galve, Miguel Palomino, Susana Valencia, Fernando Rey, Germán Sastre, Iñigo J. Vitórica-Yrezábal, Mónica Jiménez-Ruiz, J. Alberto Rodríguez-Velamazán, Miguel A. González, José L. Jordá, Eugenio Coronado, Guillermo Mínguez Espallargas|2017|Chemical Science|8|3109|doi:10.1039/C6SC05122G
CCDC 1439096: Experimental Crystal Structure Determination
Related Article: Mónica Giménez-Marqués, Néstor Calvo Galve, Miguel Palomino, Susana Valencia, Fernando Rey, Germán Sastre, Iñigo J. Vitórica-Yrezábal, Mónica Jiménez-Ruiz, J. Alberto Rodríguez-Velamazán, Miguel A. González, José L. Jordá, Eugenio Coronado, Guillermo Mínguez Espallargas|2017|Chemical Science|8|3109|doi:10.1039/C6SC05122G
CCDC 1473651: Experimental Crystal Structure Determination
Related Article: Mónica Giménez-Marqués, Néstor Calvo Galve, Miguel Palomino, Susana Valencia, Fernando Rey, Germán Sastre, Iñigo J. Vitórica-Yrezábal, Mónica Jiménez-Ruiz, J. Alberto Rodríguez-Velamazán, Miguel A. González, José L. Jordá, Eugenio Coronado, Guillermo Mínguez Espallargas|2017|Chemical Science|8|3109|doi:10.1039/C6SC05122G
CCDC 1473652: Experimental Crystal Structure Determination
Related Article: Mónica Giménez-Marqués, Néstor Calvo Galve, Miguel Palomino, Susana Valencia, Fernando Rey, Germán Sastre, Iñigo J. Vitórica-Yrezábal, Mónica Jiménez-Ruiz, J. Alberto Rodríguez-Velamazán, Miguel A. González, José L. Jordá, Eugenio Coronado, Guillermo Mínguez Espallargas|2017|Chemical Science|8|3109|doi:10.1039/C6SC05122G
CCDC 1473654: Experimental Crystal Structure Determination
Related Article: Mónica Giménez-Marqués, Néstor Calvo Galve, Miguel Palomino, Susana Valencia, Fernando Rey, Germán Sastre, Iñigo J. Vitórica-Yrezábal, Mónica Jiménez-Ruiz, J. Alberto Rodríguez-Velamazán, Miguel A. González, José L. Jordá, Eugenio Coronado, Guillermo Mínguez Espallargas|2017|Chemical Science|8|3109|doi:10.1039/C6SC05122G
CCDC 1473653: Experimental Crystal Structure Determination
Related Article: Mónica Giménez-Marqués, Néstor Calvo Galve, Miguel Palomino, Susana Valencia, Fernando Rey, Germán Sastre, Iñigo J. Vitórica-Yrezábal, Mónica Jiménez-Ruiz, J. Alberto Rodríguez-Velamazán, Miguel A. González, José L. Jordá, Eugenio Coronado, Guillermo Mínguez Espallargas|2017|Chemical Science|8|3109|doi:10.1039/C6SC05122G