Reversible folding–unfolding, aggregation protection, and multi-year stabilization, in high concentration protein solutions, using ionic liquids

Byrne, Nolene; Wang, Limin; Bélières, Jean-Philippe; Angell, C. Austen

doi:10.1039/b618943a

Cited by 213 publications

(204 citation statements)

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“…Fujita et al 30 have recently reported that the protein cytochrome c is remarkably stablilized in solution in a nontoxic dihydrogen phosphate IL, and we have found 31 that lysozyme in It is well-known from standard biological concentration solution studies that each protein has pH range in which its native state is most preferred and that deviations from that pH range can affect its folding energy and its stability against such undesirable behavior as aggregation, and recently, fibrillization. It might be expected that the proton activity of the solvent will exert a strong effect on the stability of proteins in the ionic liquid protective solution, and this is verified by our findings, 32 which are shown in Figure 12.…”

Section: Proton Activity and Protein Stabilization In Pilssupporting

confidence: 52%

Parallel Developments in Aprotic and Protic Ionic Liquids: Physical Chemistry and Applications

2007

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This Account covers research dating from the early 1960s in the field of low-melting molten salts and hydrates,which has recently become popular under the rubric of "ionic liquids". It covers understanding gained in the principal author's laboratories (initially in Australia, but mostly in the U.S.A.) from spectroscopic, dynamic, and thermodynamic studies and includes recent applications of this understanding in the fields of energy conversion and biopreservation. Both protic and aprotic varieties of ionic liquids are included, but recent studies have focused on the protic class because of the special applications made possible by the highly variable proton activities available in these liquids.In this Account, we take a broad view of ionic liquids (using the term in its current sense of liquids comprised of ions and melting below 100°C). We include, along with the general cases of organic cation systems, liquids in which common inorganic cations (like Mg 2+ and Ca 2+ ) strongly bind a hydration or solvation shell and then behave like large cation systems and melt below 100°C.We will try to organize a wide variety of measurements on low-melting ionic liquid systems into a coherent body of knowledge that is relevant to the ionic liquid field as it is currently developing.Under the expanded concept of the field, ionic liquid studies commenced in the Angell laboratory in 1962 with a study of the transport properties of the hydrates of Mg(NO 3 ) 2 and Ca(NO 3 ) 2 . These were described as melts of "large weak-field cations" 1 and their properties correlated with those of normal anhydrous molten salts via their effective cation radii, the sum of the normal radius plus one water molecule diameter. This notion was followed in 1966 with a full study under the title "A new class of molten salt mixtures" in which the hydrated cations were treated as independent cation species. The large cations mixed ideally with ordinary inorganic cations such as Na + and K + , to give solutions in which such cohesion indicators as the glass transition temperature, T g , changed linearly with composition. The concept proved quite fruitful, and a field ("hydrate melts" or "solvate melts") developed in its wake in which asymmetric anions like SCN -and NO 2 -were used with solvated cations to create a very wide range of systems that were liquid at room temperature, while remaining ionic in their general properties.The validity of the molten salt analogy was given additional conviction by the observation that transition metal ions such as Ni(II) and Co(II) could be found in the complex anion states NiCl 4 2-and CoCl 4 2-when added to the "hydrate melt" chlorides. 2 Of special interest here was the observation 3 of extreme downfield NMR proton chemical shifts of hydrate protons when the hydrated cation was Al 3+ . These lay much further downfield than did the protons in strong mineral acids at the same concentration, leading to the design of solutions of highly acidic character from salts that would usually be considered neutral. Inde...

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Section: Proton Activity and Protein Stabilization In Pilssupporting

confidence: 52%

Parallel Developments in Aprotic and Protic Ionic Liquids: Physical Chemistry and Applications

2007

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“…(i) Kill bacteria (O'Toole et al 2012); (ii) Extract, purify, and even store DNA at ambient temperature (Clark et al 2015(Clark et al , 2016; (iii) Stabilize proteins and enzymes Venkatesu 2014, Kumar et al 2017); (iv) Assist or prevent protein amyloidogenesis, and in some cases even return amyloid fibers to functional proteins (Byrne et al 2007, Byrne and Angell 2008, 2009);…”

Section: Introductionmentioning

confidence: 99%

“…Multi-lamellar structures can also be formed Fig. 1 Chemical sketches of some selected RTILs cations: (a),(b),(c) the most common imidazolium and pyrridinium RTIL cations; (d),(e) the doubletail lipid-mimic imidazoliumbased RTILs (Wang et al 2015a); (f),(g) the ethylammonium and guanidinium RTIL cations that help and contrast protein amyloidogenesis, respectively (Byrne et al 2007, Byrne and Angell 2008, 2009); (h) a phosphonium-based RTIL cation; and (i),(l) the choline and phosphocholine cations also used in RTILs made of amino acids (Benedetto et al 2014a) between RTILs and model biomembranes. Their aim is to determine the microscopic mechanisms behind their observed biological effects.…”

Section: Introductionmentioning

confidence: 99%

Room-temperature ionic liquids meet bio-membranes: the state-of-the-art

Benedetto

2017

Biophys Rev

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Room-temperature ionic liquids (RTIL) are a new class of organic salts whose melting temperature falls below the conventional limit of 100°C. Their low vapor pressure, moreover, has made these ionic compounds the solvents of choice of the so-called green chemistry. For these and other peculiar characteristics, they are increasingly used in industrial applications. However, studies of their interaction with living organisms have highlighted mild to severe health hazards. Since their cytotoxicity shows a positive correlation with their lipophilicity, several chemical-physical studies of their interactions with biomembranes have been carried out in the last few years, aiming to identify the molecular mechanisms behind their toxicity. Cation chain length and anion nature of RTILs have seemed to affect lipophilicity and, in turn, their toxicity. However, the emerging picture raises new questions, points to the need to assess toxicity on a case-by-case basis, but also suggests a potential positive role of RTILs in pharmacology, bio-medicine and bio-nanotechnology. Here, we review this new subject of research, and comment on the future and the potential importance of this emerging field of study.

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“…ILs can be employed as a new class of solvents as many biological molecules (proteins, amino acids, DNA, sugars, and polysaccharides) can be solubilized in them without loss of their bioactivity (103). This specific property seems to be particularly relevant for the field of biosensing because ILs can provide an effective way to overcome the stability limitations of these sensors related to the limited temperature range and the very narrow pH range for protein stability in water (88).…”

Section: Ionic Liquids In Biosensorsmentioning

confidence: 99%

“…For instance, it was reported that cytochrome-c can be stored in hydrated choline dihydrogenphosphate for up to 18 months without losing its activity (102). Moreover, lysozyme was stabilized against denaturation during thermal cycles in aqueous media containing an equal mass fraction of ethylammonium nitrate while the unfolding/refolding of the protein is not possible when the IL was not added (103). Yang et al (104) first demonstrated the use of ILs as electrolytes for the development of organic electrochemical transistors (OECTs) for glucose sensing.…”

Section: Ionic Liquids In Biosensorsmentioning

confidence: 99%

Properties and Customization of Sensor Materials for Biomedical Applications

Zuliani¹,

Curto²,

Matzeu³

et al. 2014

Comprehensive Materials Processing

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Reversible folding–unfolding, aggregation protection, and multi-year stabilization, in high concentration protein solutions, using ionic liquids

Abstract: We report the reversible thermal unfolding/refolding, and long period stabilization against aggregation and hydrolysis, of >200 mg ml(-1) solutions of lysozyme in ionic liquid-rich, ice-avoiding, solvents.

Cited by 213 publications

References 24 publications

Parallel Developments in Aprotic and Protic Ionic Liquids: Physical Chemistry and Applications

Parallel Developments in Aprotic and Protic Ionic Liquids: Physical Chemistry and Applications

Room-temperature ionic liquids meet bio-membranes: the state-of-the-art

Properties and Customization of Sensor Materials for Biomedical Applications

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