Organic & Biomolecular Chemistry View Article Online
EDITORIAL
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Editorial: Recognition and reactivity at interfaces† Cite this: Org. Biomol. Chem., 2015, 13, 3508
Paolo Scrimin
DOI: 10.1039/c5ob90040a
Published on 26 February 2015. Downloaded on 14/09/2015 18:51:59.
www.rsc.org/obc
The idea to launch a call for contributions for a themed collection in the field of “Recognition and Reactivity at Interfaces” came during one of the meetings of the Editorial Board of Organic & Biomolecular Chemistry during my tenure on the board and it was immediately and enthusiastically accepted. One might argue that such a topic is slightly off the scope of the journal. Organic & Biomolecular Chemistry publishes research and reviews on topics including organic synthesis, physical organic chemistry, supramolecular chemistry and chemical biology. Where are interfaces? Although we like to study recognition events and reactions in homogeneous solvents, for the very simple reason that it is easy, this doesn’t mean that in the “real world” this is the rule, rather, it is the opposite. For instance many reactions at the cellular level involve hydrophobic molecules in spite of the fact that the biological solvent is water. This is obviously only possible because of the co-existence of different phases (and interfaces, obviously!) each one with its own properties. Also one should remember how many synthetic catalytic processes occur at the interface, solid–liquid or solid–air, with incredible efficiency. The list of examples could continue. Indeed interfacial recognition events and reactivity have been intriguing
Department of Chemical Sciences, University of Padova, Via Marzolo 1, Padova, 35131, Italy. E-mail: [email protected] † See all articles in the collection: http://rsc.li/obrecog-react
3508 | Org. Biomol. Chem., 2015, 13, 3508–3509
scientists for many years. The region separating two different phases is characterized by unique properties totally different from those of the bulk. This is the case for biological membranes as well as the surface of nanomaterials. The flattering number of colleagues who accepted the invitation confirmed the interest. The collection currently features 12 articles (2 reviews, 2 communications and 8 papers) and a few more will be likely accepted in the coming weeks. Browsing through them gives a fair idea of the breadth of the field. Typical systems characterized by important processes occurring at the interface are constituted by lipid aggregates like biological membranes. One critical process is the transfection of genes addressed by Bhattacharya et al. Typically biological membranes are impermeable to polyanions (like DNA) and the masking of the charge as well as the lipophilicity are key requirements for the process to occur. In their paper (Org. Biomol. Chem., 2015, 13, 2444–2452; DOI: 10.1039/C4OB02063D) they show that α-tocopherol-derived lipid dimers behave as efficient gene transfection agents. These cationic, gemini lipids transfect plasmid DNA ( pEGFP-C3) into different cell lines without any marked toxicity in the presence of serum. Significant EGFP expression levels were reported using the gemini co-liposomes, with efficiency significantly better than the well known commercial formulation, Lipofectamine 2000. The issue of altering membrane permeability is at the center of a Communication by Matile
et al. (Org. Biomol. Chem., 2015, 13, 64–67; DOI: 10.1039/C4OB02060J). They report that the depolymerization kinetics of cell-penetrating poly(disulphide)s depend exclusively on their length and propose a kinetic uptake model to explain why their intracellular destination changes with increasing length from the endosomes over the cytosol to the nucleoli. Biological membranes are also at the center of the review by Lorent et al. (Org. Biomol. Chem., 2014, 12, 8803–8822; DOI: 10.1039/C4OB01652A) in which they illustrate that the amphiphilic nature of saponins results in relatively selective cytotoxic effects on cancer cells. This is, however, associated with the tendency of saponins to induce hemolysis. A problem that affects their use in tumor therapy. The review examines what is known on the mechanisms of saponin–membrane interactions and their consequences including the modulation of membrane dynamics, interaction with membrane rafts, and membrane lysis. The conclusions provide possible suggestions to develop new anticancer compounds. Well known model membranes are constituted of micelles and vesicles. The study of the reactivity at the interface between these amphiphilic aggregates and the bulk solvent is always attracting a lot of interest. Surfactants are present in our everyday life and their effect on chemical reactions is very important. Ghosh et al. (Org. Biomol. Chem., DOI: 10.1039/C4OB02067G) review the reactivity of hydroxamate ion towards esterolytic reactions in micelles. These α-nucleophiles may find application in
This journal is © The Royal Society of Chemistry 2015
View Article Online
Published on 26 February 2015. Downloaded on 14/09/2015 18:51:59.
Organic & Biomolecular Chemistry
the degradation of organophosphorus esters (i.e. nerve agents, pesticides and their simulants). It includes an insight into the possible nature and mechanisms of these reactions. They briefly overview also the biological activities of hydroxamic acids that have recently spurred research for application in medicine. Reverse micelles are constituted of surfactant aggregates in non-aqueous solvents. In the past these systems had been used by Luisi and other groups for enzymatic catalysis in a “unfriendly” environment. Zhao et al. report in their paper (Org. Biomol. Chem., 2015, 13, 770–775; DOI: 10.1039/C4OB02074J) the effect of prolinamide surfactants in reverse micelles on aldol reactions. By varying the headgroups of the surfactants they find that a zwitterionic one, capable of strong aggregation, presents the highest activity. The location of the catalytic groups at the surfactant–polar solvent interface is suggested, not unexpectedly, as the source of the unusual selectivity in the reaction studied. Surfactants are obviously present also in food we eat and they may regulate the transfer of antioxidants to prevent their degradation, like lipid oxidation, and preserve the organoleptic properties of lipidbased foods. This is addressed by BravoDíaz et al. (Org. Biomol. Chem., 2015, 13, 876–885; DOI: 10.1039/C4OB02058H). In their paper they have investigated the effects of temperature and surfactant volume fraction on the distribution of two representative antioxidants, the water insoluble α-tocopherol and the oil insoluble caffeic acid, in a model food emulsion composed of stripped corn oil, acidic water and the nonionic surfactant Tween 20. By using the pseudophase kinetic model they could determine the thermodynamic data and provide a rationale for the observed behavior. Interfacial and proximity issues are at the base of many reactions carried out by cyclodextrins. When these toroidshaped molecules are mixed with surfactant aggregates the resulting picture is rather complex and depend on the reaction conditions. García-Río et al. show how cyclodextrins in the presence of a surfactant modulates the chemical reactivity by multiple complexation
This journal is © The Royal Society of Chemistry 2015
Editorial
(Org. Biomol. Chem., 2015, 13, 1213–1224; DOI: 10.1039/C4OB02113D). By using 4-methoxybenzenesulfonyl chloride solvolysis as a chemical probe they show that a cooperative effect yielding a ternary complex formed by cyclodextrin–surfactant–substrate is only observed with γ-CD in comparison with β-CD because of its larger cavity. With the smaller β-CD, instead, a competitive complexation mechanism is predominant. Interfaces exist not only between two different liquids but also between a liquid and air. Kids soap bubbles constitute a popular example in this regard. Ruiz-López et al. report, from the computational point of view, on the reactivity of aldehydes (in particular their photolysis) at the air–water interface (Org. Biomol. Chem., 2015, 13, 1673–1679; DOI: 10.1039/C4OB02029D). By carrying out sequential molecular dynamics simulations and quantum mechanical calculations to analyze the influence of the air–water interface on the reactivity of formaldehyde, acetaldehyde and benzaldehyde they find that free-energy profiles exhibit a minimum at the interface, where the average reactivity indices may display large solvation effects. They also show that the photolysis rate constant of benzaldehyde in the range 290–308 nm increases by one order of magnitude at the surface of a water droplet compared to the gas phase. They discuss the potential impact of this result on the chemistry of the troposphere. (Soft) encapsulation processes rely heavily on the ability to control interfacial properties. Zhou, Huang et al. in their communication (Org. Biomol. Chem., 2015, 13, 686–690; DOI: 10.1039/ C4OB02080D) report on the preparation of polydopamine hollow nanocapsules (with a size of 200 nm and with a shell thickness of 40 nm) in a miscible tetrahydrofuran–buffer mixture. They find that an unusual non-emulsion soft template mechanism may explain the formation of the capsules. The latter structure is highly dependent on the volume fraction of tetrahydrofuran as well as the solvent, while the shell thickness can be controlled by adjusting the
reaction time and dopamine concentration. Somewhat related is the work by Coronas et al. (Org. Biomol. Chem., 2015, 13, 1724–1731; DOI: 10.1039/ C4OB01898B) in which they use the empirical Hansen solubility parameters (introduced to evaluate solvent–polymer chemical interactions) to the study caffeine encapsulation in several metal– organic frameworks. They find that this approach has much potential and could find wider application. Interfacial problems are also encountered when chemists want to functionalize a surface as shown by Ravoo et al. in their paper (Org. Biomol. Chem., 2014, 12, 7828–7835; DOI: 10.1039/ C4OB01379D) that deals with its patterning with natural and synthetic polymers via an inverse electron demand Diels– Alder reaction employing microcontact chemistry. Microcontact chemistry is a straightforward soft-lithography technique which enables fast and large area patterning with high pattern resolutions. By using tetrazine functionalized surfaces reacted with carbohydrates conjugated with norbornene or cyclooctyne acting as strained electron rich dienophiles, they show how it is possible to create monofunctional as well as bifunctional substrates specifically addressable by proteins. More technologically oriented is the contribution by Mizutani et al. (Org. Biomol. Chem., DOI: 10.1039/C4OB02053G) addressing the functionalization of silicate glass with porphyrins, carrying either a primary or tertiary alcohol, or a primary bromide linker group, via covalent bonds. The functional groups react with the surface silanol groups on silicate glass thermally at 80–240 °C to obtain a monolayer film. Their data indicate that the tertiary alcohol and the primary bromide reacted much slower than the primary alcohol. The introduction of six dodecyl chains into hydroxyporphyrin accelerates the anchoring reaction demonstrating that the dynamics of the interface is one of the dominant factors regulating the reaction kinetics. What else should I say: enjoy reading this themed issue and get inspired by the research reported.
Org. Biomol. Chem., 2015, 13, 3508–3509 | 3509
EDITORIAL
View Journal | View Issue
Editorial: Recognition and reactivity at interfaces† Cite this: Org. Biomol. Chem., 2015, 13, 3508
Paolo Scrimin
DOI: 10.1039/c5ob90040a
Published on 26 February 2015. Downloaded on 14/09/2015 18:51:59.
www.rsc.org/obc
The idea to launch a call for contributions for a themed collection in the field of “Recognition and Reactivity at Interfaces” came during one of the meetings of the Editorial Board of Organic & Biomolecular Chemistry during my tenure on the board and it was immediately and enthusiastically accepted. One might argue that such a topic is slightly off the scope of the journal. Organic & Biomolecular Chemistry publishes research and reviews on topics including organic synthesis, physical organic chemistry, supramolecular chemistry and chemical biology. Where are interfaces? Although we like to study recognition events and reactions in homogeneous solvents, for the very simple reason that it is easy, this doesn’t mean that in the “real world” this is the rule, rather, it is the opposite. For instance many reactions at the cellular level involve hydrophobic molecules in spite of the fact that the biological solvent is water. This is obviously only possible because of the co-existence of different phases (and interfaces, obviously!) each one with its own properties. Also one should remember how many synthetic catalytic processes occur at the interface, solid–liquid or solid–air, with incredible efficiency. The list of examples could continue. Indeed interfacial recognition events and reactivity have been intriguing
Department of Chemical Sciences, University of Padova, Via Marzolo 1, Padova, 35131, Italy. E-mail: [email protected] † See all articles in the collection: http://rsc.li/obrecog-react
3508 | Org. Biomol. Chem., 2015, 13, 3508–3509
scientists for many years. The region separating two different phases is characterized by unique properties totally different from those of the bulk. This is the case for biological membranes as well as the surface of nanomaterials. The flattering number of colleagues who accepted the invitation confirmed the interest. The collection currently features 12 articles (2 reviews, 2 communications and 8 papers) and a few more will be likely accepted in the coming weeks. Browsing through them gives a fair idea of the breadth of the field. Typical systems characterized by important processes occurring at the interface are constituted by lipid aggregates like biological membranes. One critical process is the transfection of genes addressed by Bhattacharya et al. Typically biological membranes are impermeable to polyanions (like DNA) and the masking of the charge as well as the lipophilicity are key requirements for the process to occur. In their paper (Org. Biomol. Chem., 2015, 13, 2444–2452; DOI: 10.1039/C4OB02063D) they show that α-tocopherol-derived lipid dimers behave as efficient gene transfection agents. These cationic, gemini lipids transfect plasmid DNA ( pEGFP-C3) into different cell lines without any marked toxicity in the presence of serum. Significant EGFP expression levels were reported using the gemini co-liposomes, with efficiency significantly better than the well known commercial formulation, Lipofectamine 2000. The issue of altering membrane permeability is at the center of a Communication by Matile
et al. (Org. Biomol. Chem., 2015, 13, 64–67; DOI: 10.1039/C4OB02060J). They report that the depolymerization kinetics of cell-penetrating poly(disulphide)s depend exclusively on their length and propose a kinetic uptake model to explain why their intracellular destination changes with increasing length from the endosomes over the cytosol to the nucleoli. Biological membranes are also at the center of the review by Lorent et al. (Org. Biomol. Chem., 2014, 12, 8803–8822; DOI: 10.1039/C4OB01652A) in which they illustrate that the amphiphilic nature of saponins results in relatively selective cytotoxic effects on cancer cells. This is, however, associated with the tendency of saponins to induce hemolysis. A problem that affects their use in tumor therapy. The review examines what is known on the mechanisms of saponin–membrane interactions and their consequences including the modulation of membrane dynamics, interaction with membrane rafts, and membrane lysis. The conclusions provide possible suggestions to develop new anticancer compounds. Well known model membranes are constituted of micelles and vesicles. The study of the reactivity at the interface between these amphiphilic aggregates and the bulk solvent is always attracting a lot of interest. Surfactants are present in our everyday life and their effect on chemical reactions is very important. Ghosh et al. (Org. Biomol. Chem., DOI: 10.1039/C4OB02067G) review the reactivity of hydroxamate ion towards esterolytic reactions in micelles. These α-nucleophiles may find application in
This journal is © The Royal Society of Chemistry 2015
View Article Online
Published on 26 February 2015. Downloaded on 14/09/2015 18:51:59.
Organic & Biomolecular Chemistry
the degradation of organophosphorus esters (i.e. nerve agents, pesticides and their simulants). It includes an insight into the possible nature and mechanisms of these reactions. They briefly overview also the biological activities of hydroxamic acids that have recently spurred research for application in medicine. Reverse micelles are constituted of surfactant aggregates in non-aqueous solvents. In the past these systems had been used by Luisi and other groups for enzymatic catalysis in a “unfriendly” environment. Zhao et al. report in their paper (Org. Biomol. Chem., 2015, 13, 770–775; DOI: 10.1039/C4OB02074J) the effect of prolinamide surfactants in reverse micelles on aldol reactions. By varying the headgroups of the surfactants they find that a zwitterionic one, capable of strong aggregation, presents the highest activity. The location of the catalytic groups at the surfactant–polar solvent interface is suggested, not unexpectedly, as the source of the unusual selectivity in the reaction studied. Surfactants are obviously present also in food we eat and they may regulate the transfer of antioxidants to prevent their degradation, like lipid oxidation, and preserve the organoleptic properties of lipidbased foods. This is addressed by BravoDíaz et al. (Org. Biomol. Chem., 2015, 13, 876–885; DOI: 10.1039/C4OB02058H). In their paper they have investigated the effects of temperature and surfactant volume fraction on the distribution of two representative antioxidants, the water insoluble α-tocopherol and the oil insoluble caffeic acid, in a model food emulsion composed of stripped corn oil, acidic water and the nonionic surfactant Tween 20. By using the pseudophase kinetic model they could determine the thermodynamic data and provide a rationale for the observed behavior. Interfacial and proximity issues are at the base of many reactions carried out by cyclodextrins. When these toroidshaped molecules are mixed with surfactant aggregates the resulting picture is rather complex and depend on the reaction conditions. García-Río et al. show how cyclodextrins in the presence of a surfactant modulates the chemical reactivity by multiple complexation
This journal is © The Royal Society of Chemistry 2015
Editorial
(Org. Biomol. Chem., 2015, 13, 1213–1224; DOI: 10.1039/C4OB02113D). By using 4-methoxybenzenesulfonyl chloride solvolysis as a chemical probe they show that a cooperative effect yielding a ternary complex formed by cyclodextrin–surfactant–substrate is only observed with γ-CD in comparison with β-CD because of its larger cavity. With the smaller β-CD, instead, a competitive complexation mechanism is predominant. Interfaces exist not only between two different liquids but also between a liquid and air. Kids soap bubbles constitute a popular example in this regard. Ruiz-López et al. report, from the computational point of view, on the reactivity of aldehydes (in particular their photolysis) at the air–water interface (Org. Biomol. Chem., 2015, 13, 1673–1679; DOI: 10.1039/C4OB02029D). By carrying out sequential molecular dynamics simulations and quantum mechanical calculations to analyze the influence of the air–water interface on the reactivity of formaldehyde, acetaldehyde and benzaldehyde they find that free-energy profiles exhibit a minimum at the interface, where the average reactivity indices may display large solvation effects. They also show that the photolysis rate constant of benzaldehyde in the range 290–308 nm increases by one order of magnitude at the surface of a water droplet compared to the gas phase. They discuss the potential impact of this result on the chemistry of the troposphere. (Soft) encapsulation processes rely heavily on the ability to control interfacial properties. Zhou, Huang et al. in their communication (Org. Biomol. Chem., 2015, 13, 686–690; DOI: 10.1039/ C4OB02080D) report on the preparation of polydopamine hollow nanocapsules (with a size of 200 nm and with a shell thickness of 40 nm) in a miscible tetrahydrofuran–buffer mixture. They find that an unusual non-emulsion soft template mechanism may explain the formation of the capsules. The latter structure is highly dependent on the volume fraction of tetrahydrofuran as well as the solvent, while the shell thickness can be controlled by adjusting the
reaction time and dopamine concentration. Somewhat related is the work by Coronas et al. (Org. Biomol. Chem., 2015, 13, 1724–1731; DOI: 10.1039/ C4OB01898B) in which they use the empirical Hansen solubility parameters (introduced to evaluate solvent–polymer chemical interactions) to the study caffeine encapsulation in several metal– organic frameworks. They find that this approach has much potential and could find wider application. Interfacial problems are also encountered when chemists want to functionalize a surface as shown by Ravoo et al. in their paper (Org. Biomol. Chem., 2014, 12, 7828–7835; DOI: 10.1039/ C4OB01379D) that deals with its patterning with natural and synthetic polymers via an inverse electron demand Diels– Alder reaction employing microcontact chemistry. Microcontact chemistry is a straightforward soft-lithography technique which enables fast and large area patterning with high pattern resolutions. By using tetrazine functionalized surfaces reacted with carbohydrates conjugated with norbornene or cyclooctyne acting as strained electron rich dienophiles, they show how it is possible to create monofunctional as well as bifunctional substrates specifically addressable by proteins. More technologically oriented is the contribution by Mizutani et al. (Org. Biomol. Chem., DOI: 10.1039/C4OB02053G) addressing the functionalization of silicate glass with porphyrins, carrying either a primary or tertiary alcohol, or a primary bromide linker group, via covalent bonds. The functional groups react with the surface silanol groups on silicate glass thermally at 80–240 °C to obtain a monolayer film. Their data indicate that the tertiary alcohol and the primary bromide reacted much slower than the primary alcohol. The introduction of six dodecyl chains into hydroxyporphyrin accelerates the anchoring reaction demonstrating that the dynamics of the interface is one of the dominant factors regulating the reaction kinetics. What else should I say: enjoy reading this themed issue and get inspired by the research reported.
Org. Biomol. Chem., 2015, 13, 3508–3509 | 3509
