Synthesis, self-assembly and lipoplex formulation of two novel cyclic phosphonate lipids
Bibliographic record
Abstract
Background: Synthetic cationic lipids hold much potential as gene packaging and delivery agents for the treatment of inherited and acquired life threatening diseases, such as cancer, AIDS, cardiovascular diseases, and certain autoimmune disorders. Methods: We report the synthesis, self-assembly as characterized by critical micelle concentrations and plasmid DNA gel retardation using two novel cyclic, phosphonate cationic lipids 2a and 2b , which were synthesized by derivatizing two diastereomeric macrocyclic phosphonates 1a and 1b with a 2-carbon hydroxylamine linker, N , N -dimethylethanolamine ( 3 ). Results: The production of cyclic phosphonate lipids 2a and 2b in 73% and 60% yields, respectively, was achieved using classical synthetic methods involving nucleophilic substitution at the phosphorus centre. The characterization of these lipids with Mass Spectrometry, 1 H, 13 C and 31 P Nuclear Magnetic Resonance supported the proposed stereochemistry and molecular structure of C 17 H 36 NO 3 P for these lipids. Critical micelle concentrations (CMC) for 2a and 2b were found to be 1.2 mM and 1.4 mM, respectively, at 25°C, providing evidence for the self-assembling ability of these novel cyclic lipids. Finally, lipid-DNA complexes (lipoplexes) formulated at various N/P (+/ − ) molar charge ratios and containing the co-lipid, 1,2-dioleoyl- sn -glycero-3-phosphoethanolamine (DOPE) were shown to retard DNA in an agarose gel retardation assay. Conclusions: The synthesis, aggregation and DNA binding properties of these novel cyclic phosphonate lipids suggest that they may have utility serving as gene packaging and delivery agents.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".