28950-57-4

Upstream product

• 3344-70-5 1,12-dibromododecane 
• 124-40-3 dimethyl amine 
• 50-00-0 formaldehyd 
• 2783-17-7 1,12-Diaminododecane 
• 4834-98-4 1,12-dodecanedioyl dichloride 
• 693-23-2 1,12-dodecanedioic acid 
• 352550-03-9 Dodecanedioic acid bis-dimethylamide 

Relevant academic research and scientific papers

Controlling Dual Molecular Pumps Electrochemically

Artificial molecular machines can be operated using either physical or chemical inputs. Light-powered motors display clean and autonomous operations, whereas chemically driven machines generate waste products and are intermittent in their motions. Herein, we show that controlled changes in applied electrochemical potentials can drive the operation of artificial molecular pumps in a semi-autonomous manner—that is, without the need for consecutive additions of chemical fuel(s). The electroanalytical approach described in this Communication promotes the assembly of cyclobis(paraquat-p-phenylene) rings along a positively charged oligomeric chain, providing easy access to the formation of multiple mechanical bonds by means of a controlled supply of electricity.

Synthesis of new cationics, carboxybetaines, and sulfobetaines bolaamphiphiles

A new family of bolaform compounds with carboxybetaine or sulfobetaine heads was synthesized in excellent yield from a common intermediate: α,w-bis-(N,N-dimethylamino)-alkane. Dicationic bolaforms bearing esters groups also were isolated.

The ionic hydrogen/deuterium bonds between diammoniumalkane dications and halide anions

Halide-anion binding to 1,12-dodecanediammonium, tetramethyl-1,12- dodecanediammmonium, and tetramethyl-1,7-heptanediammonium has been investigated with infrared multiple-photon dissociation (IRMPD) spectroscopy in the 1000-2250cm-1 spectral region and with theory. Both charged ammonium groups in these diammonium compounds interact with the halide anion resulting in an ionic hydrogen bond (IHB) stretching frequency outside of the spectral frequency range that can be measured with the free-electron laser (FEL). This frequency is shifted into the spectral range upon exchanging all of the labile hydrogen atoms with deuterium atoms, thus making measurement of the ionic deuterium bond (IDB) stretching frequency possible. The IDB stretching frequency shifts to higher values with increasing halide-anion size, methylation of the ammonium groups, and alkane chain length, consistent with the halide-anion-deuterium bond strength decreasing with decreasing gas-phase basicity of the halide anion and the increasing gas-phase basicity of the ammonium groups. The IDB stretching frequency also depends on the alkane chain length owing to constraints on the angle of the bonds between the halide anion and the two ammonium groups. There are additional bands in the IDB stretching feature in the IRMPD spectra, which are attributed to Fermi resonances and arise from coupling with overtone or combination bands that can be identified from theory and depend on the halide-anion identity and alkane chain length.

Original disymmetric bolaforms bearing at least one sulfobetaine head; synthesis and surface properties

We describe a simple and efficient method for the synthesis of disymmetric bolaforms bearing at least one sulfobetaine head. In this process, we could introduce successively on α,ω-bis(dialkylamino) alkane a sulfobetaine head and a cationic, a sulfobetaine, or a carboxybetaine head, in excellent yield. This is the first synthesis of disymmetric sulfobetaine bolaforms. The method is easily generalized to various types of head functional groups. The wide range of bolaforms produced by this method has been exploited to study their surface properties and to determine the respective roles of the polar heads and the lengths of the spacers (n) on self-aggregation in aqueous media. A critical micellar concentration (cmc) was observed with the compounds with a spacer of 12 carbon atoms (n = 12). Micellization appeared to be consistent with a "wicket-like" conformation, which did not appear to form with the n = 8 compounds.

NOVEL TRISCATIONIC AMPHIPHILE COMPOUNDS, COMPOSITIONS, AND METHODS FOR MAKING SAME

The inventive subject matter relates to compounds of Formula I and Formula II, compositions thereof, and processes for making such compounds as presently claimed and further described herein. The inventive compounds and compositions have antimicrobial properties and are useful as environmental disinfectants, topical cleansers such as topical personal care compositions, sanitizers, preservatives, in water treatment, as permanent or erodible coatings for medical devices and appliances, and in therapeutics.

Antibacterial and Antibiofilm Activity of Cationic Small Molecules with Spatial Positioning of Hydrophobicity: An in Vitro and in Vivo Evaluation

More than 80% of the bacterial infections are associated with biofilm formation. To combat infections, amphiphilic small molecules have been developed as promising antibiofilm agents. However, cytotoxicity of such molecules still remains a major problem. Herein we demonstrate a concept in which antibacterial versus cytotoxic activities of cationic small molecules are tuned by spatial positioning of hydrophobic moieties while keeping positive charges constant. Compared to the molecules with more pendent hydrophobicity from positive centers (MIC = 1-4 μg/mL and HC50 = 60-65 μg/mL), molecules with more confined hydrophobicity between two centers show similar antibacterial activity but significantly less toxicity toward human erythrocytes (MIC = 1-4 μg/mL and HC50 = 805-1242 μg/mL). Notably, the optimized molecule is shown to be nontoxic toward human cells (HEK 293) at a concentration at which it eradicates established bacterial biofilms. The molecule is also shown to eradicate preformed bacterial biofilm in vivo in a murine model of superficial skin infection.

Cleavable cationic antibacterial amphiphiles: Synthesis, mechanism of action, and cytotoxicities

The development of novel antimicrobial agents having high selectivity toward bacterial cells over mammalian cells is urgently required to curb the widespread emergence of infectious diseases caused by pathogenic bacteria. Toward this end, we have developed a set of cationic dimeric amphiphiles (bearing cleavable amide linkages between the headgroup and the hydrocarbon tail with different methylene spacers) that showed high antibacterial activity against human pathogenic bacteria (Escherichia coli and Staphylococcus aureus) and low cytotoxicity. The Minimum Inhibitory Concentrations (MIC) were found to be very low for the dimeric amphiphiles and were lower or comparable to the monomeric counterpart. In the case of dimeric amphiphiles, MIC was found to decrease with the increase in the spacer chain length (n = 2 to 6) and again to increase at higher spacer length (n > 6). It was found that the compound with six methylene spacers was the most active among all of the amphiphiles (MICs = 10-13 μM). By fluorescence spectroscopy, fluorescence microscopy, and field-emission scanning electron microscopy (FESEM), it was revealed that these cationic amphiphiles interact with the negatively charged bacterial cell membrane and disrupt the membrane integrity, thus killing the bacteria. All of the cationic amphiphiles showed low hemolytic activity (HC50) and high selectivity against both gram-positive and gram-negative bacteria. The most active amphiphile (n = 6) had a 10-13-fold higher HC50 than did the MIC. Also, this amphiphile did not show any cytotoxicity against mammalian cells (HeLa cells) even at a concentration above the MIC (20 μM). The critical micellar concentration (CMC) values of gemini surfactants were found to be very low (CMC = 0.30-0.11 mM) and were 10-27 times smaller than the corresponding monomeric analogue (CMC = 2.9 mM). Chemical hydrolysis and thermogravimetric analysis (TGA) proved that these amphiphiles are quite stable under both acidic and thermal conditions. Collectively, these properties make the newly synthesized amphiphiles potentially superior disinfectants and antiseptics for various biomedical and biotechnological applications.

A new class of bolaforms bearing sulfobetaine and cationic heads: Synthesis and aggregation properties

We describe here a convenient route to a new family of bolaforms bearing sulfobetaine and cationic heads, which could be scaled up for industrial applications. Their aggregation modes were studied by measurement of surface tension and by dynamic light scattering and transmission electronic microscopy methods. Grafting a hydrophobic chain onto the cationic head modifies both the surface properties and aggregation. Compared to conventional bolaforms, the relationship between the length of the spacer and the side-chain and the resultant hydrophobic interactions are at the origin of these novel properties. Various models of these molecular associations were proposed.

Antimalarial activity of compounds interfering with Plasmodium falciparum phospholipid metabolism: Comparison between mono- and bisquaternary ammonium salts

On the basis of a previous structure - activity relationship study, we identified some essential parameters, e.g. electronegativity and lipophilicity, required for polar head analogues to inhibit Plasmodium falciparum phospholipid metabolism, leading to parasite death. To improve the in vitro antimalarial activity, 36 cationic choline analogues consisting of mono-, bis-, and triquaternary ammonium salts with distinct substituents of increasing lipophilicity were synthesized. For monoquaternary ammonium salts, an increase in the lipophilicity around nitrogen was beneficial for antimalarial activity: IC50 decreased by I order of magnitude from trimethyl to tripropyl substituents. Irrespective of the polar head substitution (methyl, ethyl, hydroxyethyl, pyrrolidinium), increasing the alkyl chain length from 6 to 12 methylene groups always led to increased activity. The highest activity was obtained for the N,N,N-tripropyl-N-dodecyl substitution of nitrogen (IC50 33 nM). Beyond 12 methylene groups, the antimalarial activities of the compounds decreased slightly. The structural requirements for bisquaternary ammonium salts in antimalarial activity were very similar to those of monoquaternary ammonium salts, i.e. polar head steric hindrance and lipophilicity around nitrogen (methyl, hydroxyethyl, ethyl, pyrrolidinium, etc.). In contrast, with bisquaternary ammonium salts, increasing the lipophilicity of the alkyl chain between the two nitrogen atoms (from 5 to 21 methylene groups) constantly and dramatically increased the activity. Most of these duplicated molecules had activity around 1 nM, and the most lipophilic compound synthesized exhibited an IC50 as low as 3 pM (21 methylene groups). Globally, this oriented synthesis produced 28 compounds out of 36 with an IC50 lower than 1 μM, and 9 of them had an IC50 in the nanomolar range, with I compound in the picomolar range. This indicates that developing a pharmacological model for antimalarial compounds through choline analognes is a promising strategy.

Zwitterionic sulfobetaine inhibitors of squalene synthase

A substantial number of sulfobetaines (e.g., 10) have been synthesized and evaluated as inhibitors of squalene synthase (SS) on the basis of the idea that their zwitterionic structure would have properties conducive both to binding in the active site and to passage through cell membranes. When the simple sulfobetaine moiety is incorporated into compounds containing hydrophobic portions like those in farnesyl diphosphate (1) or presqualene diphosphate (2), inhibition of SS in a rat liver microsomal assay was indeed observed. For example, farnesylated sulfobetaine 10 has IC50 = 10 μM and aromatic derivative 35 has IC50 = 2 μM for SS inhibition. A wide variety of structural modifications, exemplified by compounds 43, 52, 76, 85, 91, 99, 111, and 115, was investigated. Unfortunately, no inhibitors in the submicromolar range were discovered, and exploration of a different type of zwitterion seems necessary if this appealing approach to inhibition of SS is going to provide a potential antihypercholesterolemic agent.