Bispidinone-based molecular switches for construction of stimulus-sensitive liposomal containers

Veremeeva, Polina N.; Лаптева, В. Л.; Palyulin, V. A.; Sybachin, Andrey V.; Yaroslavov, Alexander A.; Зефиров, Н. С.

doi:10.1016/j.tet.2014.01.012

Cited by 26 publications

(17 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Another group of researchers suggested 3,7-diazabicyclo[3.3.1]nonan-9-one 4 (Scheme 3) as a conformational switch for the lipid-like amphiphiles (54,55). In neutral and weakly basic media, these compounds adopt a chairboat conformation (4B) that flips into a chair-chair form (4C) in the presence of acid or upon complexation with metal cations.…”

Section: Metal-responsive Systemsmentioning

confidence: 99%

“…This effect was attributed to the complexation-induced change of conformation, which affected the package of lipids in the bilayer and sharply increased the permeability of the liposomal membrane. The liposomal containers with such flipids can be used for the encapsulation and following release of drugs that control the copper level in patients with various pathologies, e.g., hepato-cerebral dystrophy (Wilson disease) (54,55). Interestingly, the acid-or metal-triggered flip brings the hydrocarbon tails in 4 closer to each otherthe change in the direction opposite to the peacock effect observed for flipids 1 (see above).…”

Section: Metal-responsive Systemsmentioning

confidence: 99%

See 1 more Smart Citation

Fliposomes: stimuli-triggered conformational flip of novel amphiphiles causes an instant cargo release from liposomes

Samoshin

2014

Biomolecular Concepts

View full text Add to dashboard Cite

This review presents a new strategy for the design of stimuli-responsive liposomes for targeted delivery - the construction of a liposome membrane (lipid bilayer) using amphiphiles able to perform a stimuli-triggered conformational flip ('flipids'). When done simultaneously by a major or significant part of the bilayer molecules, this massive flip disrupts the liposome membrane and induces a rapid release of the liposome load specifically in response to the initial stimulus. The conformational switches incorporated into the amphiphilic molecules could potentially be controlled by various internal or external factors (pH, metal complexation, light, electric field, etc.). Using this concept, we designed a series of pH-triggerable flipids, and prepared and tested 'fliposomes' with extraordinary characteristics: high stability in storage and in serum combined with an instant release of their cargo in response to a weakly acidic medium.

show abstract

Section: Metal-responsive Systemsmentioning

confidence: 99%

Section: Metal-responsive Systemsmentioning

confidence: 99%

Fliposomes: stimuli-triggered conformational flip of novel amphiphiles causes an instant cargo release from liposomes

Samoshin

2014

Biomolecular Concepts

View full text Add to dashboard Cite

show abstract

“…This move changes dramatically their ability to interact with another molecule or ion, or to pack into lipid bilayers (depending on the nature of R). The moieties of trans ‐3,4‐bis(acyloxy)‐piperidine, trans ‐4‐amino‐3‐piperidinol, 3,7‐diazabicyclo[3.3.1]nonan‐9‐one, arylamide‐substituted diphenylacetylene, trans ‐4,5‐dihydroxyhexahydropyridazine, di(methoxyphenyl)pyridine and substituted amides, and other more complex molecular devices were also suggested recently as new pH sensitive bases for analogous applications.…”

Section: Introductionmentioning

confidence: 99%

Trans‐2‐Aminocyclohexanol derivatives as pH‐triggered conformational switches

Samoshin

Zheng

Liu

2017

J of Physical Organic Chem

View full text Add to dashboard Cite

A series of trans-2-aminocyclohexanol derivatives have been explored as powerful conformational pH triggers. On protonation of the amino group, a conformer with equatorial position of ammonio and hydroxy groups becomes predominant because of an intramolecular hydrogen bond and electrostatic interactions. The energy of these interactions was estimated to be above 10 kJ/mol and in some models exceeded 20 kJ/mol (strong enough to twist a ring in tert-butyl derivatives). As a result of this conformational flip, all other substituents are forced to change their orientation. If the substituents are designed to perform certain geometry-dependent functions, for example, as cation chelators or as lipid tails, such acid-induced transition may be used to control the corresponding molecular properties. The pH sensitivity of conformational equilibria was explored by 1 H nuclear magnetic resonance spectroscopy (NMR), and the titration curves were used for estimation of the pK a values of protonated compounds that varied from 2.6 to 8.5 (in d 4 -methanol) depending on the structure of amino group. Thus, trans-2-aminocyclohexanols can be also used as conformational pH indicators in organic solvents.

show abstract

“…In other examples, the sensing unit has been incorporated into lipid structures to drive release based on conformational changes triggered by molecular recognition events. Zefirov and co‐workers developed bispidinone‐based lipid switches that respond to copper and acid by interconverting from chair–boat form ( 4 a ) to chair–chair ( 4 b ) upon ion complexation (Scheme ). Of note in this case is that the hydrophobic chains appear to converge upon switching, which differs from the divergence of the chains in other examples we have discussed.…”

Section: Lipid Switches Triggered By Molecular Recognitionmentioning

confidence: 99%

Lipid Switches: Stimuli‐Responsive Liposomes through Conformational Isomerism Driven by Molecular Recognition

Lou

Zhang

Best

2018

Chemistry A European J

View full text Add to dashboard Cite

Advancements in the field of liposomal drug carriers have culminated in greatly improved delivery properties. An important aspect of this work entails development of designer liposomes for release of contents triggered by environmental changes. The majority of these systems are driven by chemical reactions in the presence of different stimuli. However, a promising new paradigm instead focuses on molecular recognition events as the impetus for content release. In certain cases, these platforms exploit synthetic lipid switches designed to undergo conformational changes upon binding to target ions or molecules that perturb membrane assembly, thereby triggering cargo release. Examples of this approach reported thus far showcase how rational design of lipid switches can result in dramatic changes in lipid assembly properties. These strategies show great promise for opening up new pathophysiological stimuli that can be harnessed for programmed content release in drug delivery applications.

show abstract

Bispidinone-based molecular switches for construction of stimulus-sensitive liposomal containers

Cited by 26 publications

References 16 publications

Fliposomes: stimuli-triggered conformational flip of novel amphiphiles causes an instant cargo release from liposomes

Fliposomes: stimuli-triggered conformational flip of novel amphiphiles causes an instant cargo release from liposomes

Trans‐2‐Aminocyclohexanol derivatives as pH‐triggered conformational switches

Lipid Switches: Stimuli‐Responsive Liposomes through Conformational Isomerism Driven by Molecular Recognition

Contact Info

Product

Resources

About