The present invention provides amphiphilic diacetylene compounds, and compositions and self-assembled nanotubes containing the same. Also provided are methods of producing the compounds, compositions, and nanotubes of the invention, and methods of destroying or inhibiting the growth or proliferation of microorganisms using the nanotubes of the present invention.

Description of the Invention

SUMMARY OF THE INVENTION

The present invention generally provides a compound having formula (I), and salts thereof: W--C.ident.C--C.ident.C--V-L-QX (I) Wherein,

the moiety W--C.ident.C--C.ident.C--V is a bilayer-compatible hydrophobic chain;

L is a linker comprising a chain of from 1 to 10 atoms;

Q is --NR.sub.2 or --NR'R.sub.2.sup.+;

X is an anion, present only when Q is --NR'R.sub.2.sup.+;

each R is independently selected from the group consisting of H, C.sub.1-C.sub.8 alkyl and C.sub.6-C.sub.10 aryl; each R independently being unsubstituted or substituted with one or more substituents selected from the group consisting of halogen, oxo, acyl, alkenyl, alkoxyl, alkyl, alkylamino, amino, aryl, cycloalkyl, heterocyclyl, and heterocyclylalkyl, with the proviso that at least one R is not H; and

R' is C.sub.1-C.sub.8 alkyl, optionally substituted with at least one selected from the group consisting of halogen, oxo, acyl, alkenyl, alkoxyl, alkyl, alkylamino, amino, aryl, cycloalkyl, heterocyclyl, and heterocyclylalkyl.

The invention also provides nanostructures containing one or more compounds of formula (I).

In certain embodiments, the compound is selected from the group consisting of N-10,12-pentacosadiynoyl-N'-ethylethylenediamine hydrobromide ("compound 3"), N-10,12-pentacosadiynoyl-N',N'-diethylethylenediamine hydrobromide ("compound 4"), N-10,12-pentacosadiynoyl-N',N',N'-triethylethylenediammonium bromide ("compound 5"), N-10,12-pentacosadiynoyl-N'-ethylethylenediamine ("compound 6"), and N-10,12-pentacosadiynoyl-N',N'-diethylethylenediamine ("compound 7").

In one aspect, the present invention also provides a method for preparing a compound having formula (I), wherein W is CH.sub.3(CH.sub.2)a- and V is --(CH.sub.2)b- and wherein a+b is from about 4 to about 30, which comprises reacting a compound having formula (II): CH.sub.3(CH.sub.2).sub.a--C.ident.C--C.ident.C--(CH.sub.2).sub.b--COOH (II) in a reaction mixture with a diamine compound having formula (III): H.sub.2N-L'-NR.sub.2 (III) in the presence of a carboxylic acid activating reagent, thereby producing a compound having formula (IV): CH.sub.3(CH.sub.2).sub.a--C.ident.C--C.ident.C--(CH.sub.2).sub.b--CONH-L'- -NR.sub.2 (IV) and, optionally, reacting the compound having formula (IV) with an alkylating agent R'--Y, thereby producing the compound of formula (V), CH.sub.3(CH.sub.2).sub.a--C.ident.C--C.ident.C--(CH.sub.2).sub.b--CO- NH-L'-NR'R.sub.2.sup.+X.sup.- (IV) wherein,

a+b is from about 4 to about 30;

L' is selected from the group consisting of CH.sub.2CH.sub.2, CH.sub.2CH.sub.2CH.sub.2, and CH.sub.2CH.sub.2ZCH.sub.2CH.sub.2;

where Z is selected from the group consisting of CH.sub.2, O, S, and NR;

X is a leaving group;

each R is independently selected from the group consisting of hydrogen, C.sub.1-C.sub.8 alkyl, and C.sub.6-C.sub.14 aryl, wherein each R is optionally substituted with at least one selected from the group consisting of halogen, oxo, acyl, alkenyl, alkoxyl, alkyl, alkylamino, amino, aryl, cycloalkyl, heterocyclyl, and heterocyclylalkyl; and

R' is C.sub.1-C.sub.8 alkyl, optionally substituted with at least one selected from the group consisting of halogen, oxo, acyl, alkenyl, alkoxyl, alkyl, alkylamino, amino, aryl, cycloalkyl, heterocyclyl, and heterocyclylalkyl.

Suitable carboxylic acid activating reagents are well-known in the art, and include but are not limited to carbodiimides, thionyl chloride, and oxalyl chloride, and preferably include catalysts such as N-hydroxysuccinimide, N-hydroxybenzotriazole, and N,N-dimethylaminopyridine. In general, reagents suitable for peptide synthesis will also be useful for the preparation of compounds of formula (IV).

In one embodiment, the compound having formula (II) is 10,12-pentacosadiynoic acid. In certain embodiments, the diamine compound having formula (III) may be selected from the group consisting of 1,2-diaminoethane, N.sup.1-ethyl-1,2-diaminoethane, and N.sup.1,N.sup.1-diethyl-1,2-diaminoethane. In still other embodiments, the activated derivative is an N-hydroxysuccinimidate ester. In yet another embodiment, the N-hydroxysuccinimidate ester is prepared by reaction of structure (II) with N-hydroxysuccinimide in the presence of a carbodiimide. Suitable carbodiimides include but are not limited to 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide and N,N'-dicyclohexylcarbodiimide. Suitable alkylating agents include but are not limited to methyl iodide, bromoethane, and 1-bromopropane.

In another aspect, the present invention provides a method of forming a nanotube, including the steps of: (a) adding a non-polar solvent to a solution containing a plurality of amphiphilic non-chiral single-chain diacetylenic compounds to form a reaction solution; (b) drying the reaction solution, thereby forming a primitive structure; (c) preparing a primitive structure solution containing the primitive structure; (d) sonicating the primitive structure solution; and (e) drying the primitive structure solution, thereby forming the nanotubes.

In one embodiment, the non-polar solvent may be hexane, heptane, or cyclohexane. In another embodiment, the reaction solution may contain dichloromethane, chloroform, or carbon tetrachloride. In yet another embodiment, the primitive structure solution may contain a solvent, such as, without limitation, H.sub.2O, hexane, chloroform, and carbon tetrachloride. In still another embodiment, the method further includes a step of applying the primitive structure solution onto a substrate (e.g., a glass) before the step (e). In addition, at least one of the plurality of amphiphilic non-chiral single-chain diacetylenic compounds may be a compound having formula (I).

In addition, the present invention provides a method of forming a "nanocarpet" supramolecular assembly of nanotubes, including the steps of: (a) adding a non-polar solvent to an initiation solution, wherein the initiation solution contains a plurality of amphiphilic non-chiral single-chain diacetylenic compounds; (b) drying the initiation solution, thereby forming a primitive structure; (c) preparing a primitive structure solution containing the primitive structure; (d) sonicating the primitive structure solution; (e) treating the primitive structure solution with ultraviolet light (e.g., ultraviolet light having a wavelength of about 254 nm); (f) partially drying the primitive structure solution, thereby forming a secondary structure; (g) adding a secondary structure solvent to the secondary structure; and (h) drying the secondary structure, thereby forming the nanocarpet. In one embodiment, the secondary structure solvent may be chloroform, dichloromethane, carbon tetrachloride, ethyl acetate, or ethyl ether.

The present invention further provides a method of forming a nanocarpet, including the steps of: (a) partially drying an initiation solution containing a plurality of amphiphilic non-chiral single-chain diacetylenic compounds, thereby forming a intermediate structure; (b) adding an aqueous solution to the partially dried intermediate structure; (c) treating the intermediate structure with ultraviolet light or .gamma.-ray irradiation; and (d) drying the intermediate structure, thereby forming the nanocarpet.

In addition, the invention provides an improved method for polymerization of the nanotubes, which comprises dispersing the nanotubes on a support surface prior to irradiation. This is an improvement over solution polymerization, which is difficult to carry out to completion, and provides high yields of polymerized nanotubes (PNTs).

Also provided is a method of destroying or inhibiting the growth or proliferation of a microorganism (e.g., a bacterium or a fungus), by contacting the microorganism with one or more nanotubes of the present invention.

Other feature and advantages of the present invention will become apparent from the following detailed description. It should be understood that the detailed description and the specific examples, while indicating the preferred embodiments of the invention, are given by way of illustration only. Various changes and modifications will be apparent to those skilled in the art, and remain within the spirit and scope of the invention.

DETAILED DESCRIPTION OF THE INVENTION

As used herein and in the appended claims, the singular forms "a," "an," and "the" include plural references unless the content clearly dictates otherwise. Thus, for example, reference to "a diamine compound" includes a plurality of such diamine compounds and equivalents thereof known to those skilled in the art, and so forth, and reference to "the nanotube" is a reference to one or more such nanotubes and equivalents thereof known to those skilled in the art, and so forth. All publications, patent applications, patents, and other references mentioned herein are incorporated by reference in their entirety.

The present invention generally provides novel, amphiphilic non-chiral single-chain diacetylenic amphiphiles, and methods of synthesizing the same. The present invention also generally provides a method of producing nearly homogeneous monodisperse microstructures, such as, nanotubes (e.g., nanotubes with uniform diameter), nanocarpets, "nanocrackers," "nanohands," and the microstructures produced therewith. The remarkable self-assembly of these inexpensive and simple lipid compounds is unprecedented and represents a real step toward the rational design of nanostructured materials for a plethora of applications in fields, such as electronics, optics, biosensors, and pharmaceutics.

In one aspect, the present invention provides amphiphilic diacetylene compounds having formula (I): W--C.ident.C--C.ident.C--V-L-QX (I) wherein,

the moiety W--C.ident.C--C.ident.C--V is a bilayer-compatible hydrophobic chain;

L is a linker comprising a chain of from 1 to 10 atoms;

Q is --NR.sub.2 or --NR'R.sub.2.sup.+;

X is an anion, present only when Q is --NR'R.sub.2.sup.+;

each R is independently selected from the group consisting of H, C.sub.1-C.sub.8 alkyl and C.sub.6-C.sub.10 aryl; each R independently being unsubstituted or substituted with one or more substituents selected from the group consisting of halogen, oxo, acyl, alkenyl, alkoxyl, alkyl, alkylamino, amino, aryl, cycloalkyl, heterocyclyl, and heterocyclylalkyl, with the proviso that at least one R is not H; and

R' is C.sub.1-C.sub.8 alkyl, optionally substituted with at least one selected from the group consisting of halogen, oxo, acyl, alkenyl, alkoxyl, alkyl, alkylamino, amino, aryl, cycloalkyl, heterocyclyl, and heterocyclylalkyl.

As used herein and in the appended claims, alkyl and alkenyl groups, as well as the alkyl and alkenyl moieties of other groups (e.g., alkoxy and alkylamino) may have up to eight carbon atoms, and they may be linear or branched, or comprise carbocyclic rings (e.g., isopropyl, t-butyl, cyclopentyl, cyclopropylmethyl, and the like). The term "aryl" encompasses phenyl, naphthyl, anthracenyl, and pyrenyl ring systems, and does not exclude the possibility of simple substituents. A heterocyclyl group may be any member of the group consisting of saturated, partially saturated, and unsaturated mono-, bi-, and tri-cyclic ring structures, having up to 14 ring atoms, wherein at least one atom of a ring is nitrogen, oxygen, or sulfur. The term "halogen" or "halide," as used herein and in the appended claims, includes fluorine (F), chlorine (Cl), bromine (Br), and iodine (I).

Bilayer-compatible hydrophobic chains are hydrocarbon chains of such a length that molecules of formula I will spontaneously self-assemble into bilayers at some temperature between about 0.degree. C. and 100.degree. C., when a solution of the compound is diluted with a non-solvent such as water or heptane. Hydrocarbon moieties that are too short do not experience sufficient van der Waals attractive forces to self-assemble, whereas chains that are too long will be disordered and the molecules will face an entropic barrier to alignment of the chains. Suitable candidates include but are not limited to linear hydrocarbon chains from about 8 to about 40 carbons in length. Preferably, the bilayer-compatible chain is between about 10 and about 30 carbons in length. The chains may optionally be modified, for example by halogenation or by incorporation of carbocylic rings, to modify their properties.

L is a "spacer" of from one to ten atoms in length. Suitable spacers include, but are not limited to, atom chains comprising CH.sub.2CH.sub.2, CH.sub.2CH.sub.2CH.sub.2, CH.sub.2CH.sub.2OCH.sub.2CH.sub.2, CH.sub.2CH.sub.2SCH.sub.2CH.sub.2, CH.sub.2CH.sub.2NHCH.sub.2CH.sub.2 and CH.sub.2CH.sub.2NRCH.sub.2CH.sub.2, and may optionally incorporate keto, ester, or amide moieties. Preferably the spacer comprises an amide, and most preferably L is selected from CONHCH.sub.2CH.sub.2, CONHCH.sub.2CH.sub.2CH.sub.2, CONHCH.sub.2CH.sub.2OCH.sub.2CH.sub.2, CONHCH.sub.2CH.sub.2SCH.sub.2CH.sub.2, and CONHCH.sub.2CH.sub.2NHCH.sub.2CH.sub.2.

In one embodiment, a is 10 and b is 7. Examples of the diacetylenic compounds of the present invention include, without limitation, N-(10,12-pentacosadiynoyl)-N'-ethylethylenediamine hydrobromide (compound 3), N-(10,12-pentacosadiynoyl)-N',N'-diethylethylenediamine hydrobromide (compound 4), N-(10,12-pentacosadiynoyl)-N',N',N'-triethylethylenediamine hydrobromide (compound 5), N-(10,12-pentacosadiynoyl)-N'-ethylethylenediamine (compound 6), and N-(10,12-pentacosadiynoyl)-N',N'-diethylethylenediamine (compound 7).

In another aspect, the present invention provides a method for preparing a compound having the formula (I), wherein W is CH.sub.3(CH.sub.2)a- and V is --(CH.sub.2)b- and wherein a+b is from about 4 to about 30, which comprises reacting an activated derivative of a compound having formula (II): CH.sub.3(CH.sub.2).sub.a--C.ident.C--C.ident.C--(CH.sub.2).sub.b--C- OOH (II) in a reaction mixture with a diamine compound having formula (III): H.sub.2N-L'-NR.sub.2 (III) in the presence of a carboxylic acid activating reagent, thereby producing a compound having formula (IV): CH.sub.3(CH.sub.2).sub.a--C.ident.C--C.ident.C--(CH.sub.2).sub.b--CONH-L'- -NR.sub.2 (IV) and, optionally, reacting the compound having formula (IV) with an alkylating agent R'--Y, thereby producing the compound of formula (V), CH.sub.3(CH.sub.2).sub.a--C.ident.C--C.ident.C--(CH.sub.2).sub.b--CO- NH-L'-NR'R.sub.2.sup.+X.sup.- (V) wherein,

a+b is from about 4 to about 30;

L' is selected from the group consisting of CH.sub.2CH.sub.2, CH.sub.2CH.sub.2CH.sub.2, and CH.sub.2CH.sub.2ZCH.sub.2CH.sub.2;

where

Z is selected from the group consisting of CH.sub.2, O, S, and NR;

X is a leaving group;

each R is independently selected from the group consisting of hydrogen, C.sub.1-C.sub.8 alkyl, and C.sub.6-C.sub.14 aryl, wherein each R is optionally substituted with at least one selected from the group consisting of halogen, oxo, acyl, alkenyl, alkoxyl, alkyl, alkylamino, amino, aryl, cycloalkyl, heterocyclyl, and heterocyclylalkyl; and

R' is C.sub.1-C.sub.8 alkyl, optionally substituted with at least one selected from the group consisting of halogen, oxo, acyl, alkenyl, alkoxyl, alkyl, alkylamino, amino, aryl, cycloalkyl, heterocyclyl, and heterocyclylalkyl.

In one embodiment, a novel diacetylenic compound of the present invention may be prepared by using the following process: a diacetylenic lipid having formula, CH.sub.3(CH.sub.2).sub.mC.ident.C--C.ident.C(CH.sub.2).sub.nCOOH (m=9, 11, or 13 and n=8 or 10), such as 10,12-pentacosadiynoic acid (PDA), may be converted to a succinimidyl ester in the presence of a N-hydroxysuccinimide (NHS) and a carbodiimide. Examples of carbodiimides include, but are not limited to, 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide (DEC) and N,N'-dicyclohexylcarbodiimide (DCC). Alternately, the diacetylenic acid may be converted to an acyl halide, for example by reacting with oxalyl chloride or thionyl chloride.

The modified diacetylenic lipids prepared as above may be slowly added to an excess amount of an appropriate diamine in a chlorinated solvent (e.g., chloroform and dichloromethane) or tetrahydrofuran. After the reaction, the mixture may be extracted with chloroform, dichloromethane, or ethyl acetate, and then washed with water. The organic phase may be dried with a drying agent (e.g., Na.sub.2SO.sub.4, MgSO.sub.4, or CaCl.sub.2) and evaporated (e.g., by using a rotary evaporator), typically yielding a white powder (e.g., compound 2 as shown in FIG. 1, see Original Patent). The compounds may be further processed by quaternization at room temperature in a solvent, such as chloroform, nitromethane, or acetonitrile. The solvents may be removed by using a rotary evaporator to yield the desired diacetylenic compound (e.g., compounds 3, 4, and 5 as shown in FIG. 1).

In another embodiment, a novel diacetylenic compound of the present invention may be prepared using the following process: a diacetylenic lipid having formula, CH.sub.3(CH.sub.2).sub.aC.ident.C--C.ident.C(CH.sub.2).sub.bCOOH (a=9, 11, or 13 and b=8 or 10), such as, 10,12-pentacosadiynoic acid (PDA), converted to the NHS ester or acyl chloride, may be slowly added to an excess of an appropriate N-alkylalkylenediamine in a chlorinated solvent (e.g., chloroform or dichloromethane) or tetrahydrofuran. After the reaction, the mixture may be washed with water. The organic phase may be dried with a drying agent (e.g., Na.sub.2SO.sub.4, MgSO.sub.4 or CaCl.sub.2) and evaporated (e.g., by using a rotary evaporator) to yield the N-alkylalkylenediamine derivative of the diacetylenic lipid substrate (e.g., compound 6 as shown in FIG. 1). The compounds are further processed by reacting with a mineral acid, e.g., by adding HBr aqueous solution into an alcohol (e.g., methanol, ethanol, isopropyl alcohols), chlorinated solvent (e.g., chloroform and dichloromethane), or tetrahydrofuran solution of the N-alkylalkylenediamine derivative of the diacetylenic lipid substrate. The solvents may be removed by using a rotary evaporator to yield the desired diacetylenic compound (e.g., compounds 3 or 4, as shown in FIG. 1).

The present invention further provides methods for producing a microstructure containing a plurality of amphiphilic non-chiral single-chain diacetylenic compounds, such as, compounds of the formula (I), and the microstructure produced therewith. As used herein and in the appended claims, the term "microstructure" includes a structure having at least one dimension within a range of about 0.5 nm to about 100 .mu.m. In one embodiment, at least one dimension of the microstructure may be within a range of about 5 nm to about 1000 nm. In another embodiment, at least one dimension of the microstructure may be within a range of about 50 nm to about 500 nm. Examples of the microstructure include, without limitation, micrometer sized tubules, nanotubes, nanocarpets, nanocrackers, and nanohands. As used herein and in the appended claims, the terms "nanotube," "nanocracker," or "nanohand," refer to a tubular-shaped, a cracker-shaped, or a hand-shaped microstructure, respectively, having at least one dimension within a range of about 0.5-1000 nm, while the term "nanocarpet" refers to a microstructure having a plurality of clustered nanotubes. In one embodiment, at least one dimension of the nanotube, nanocarpet, nanocracker, or nanohand may be within a range of about 5 nm to about 800 nm. In another embodiment, at least one dimension of the microstructure may be within the range of about 50 nm to about 500 nm. Examples of the nanotubes, nanocarpets, nanocrackers, or nanohands are shown in FIG. 2 (see Original Patent).

In one aspect, the present invention provides a microstructure containing a plurality of nanotubes, wherein the nanotubes are of uniform diameter and are formed by self-assembly of one or more amphiphilic non-chiral single-chain diacetylenic compounds. As used herein in reference to an individual preparation of nanotubes, the term "uniform diameter" means that at least 95% of the nanotubes have a diameter within 10% and/or within 5 nm of the mean diameter of all the nanotubes in the composition.

For example, at least one of the amphiphilic non-chiral single-chain diacetylenic compounds may have the structure: W--C.ident.C--C.ident.C--V-L-QX wherein the moiety W.ident.C--C.ident.C--V is a bilayer-compatible hydrophobic chain, L is a linker including a chain of from 1 to 10 atoms, and Q and X together are an ion pair. In one embodiment, W may be a C.sub.3 to C.sub.20 alkyl group. In another embodiment, V may be a C.sub.1 to C.sub.20 alkylene group. In yet another embodiment, L may be a --CONH(CH.sub.2).sub.m-- group and m is about 2-8. In still another embodiment, Q is a protonated secondary amine, such as, a --NH.sub.2R.sup.+ group, wherein R is a C.sub.1-C.sub.8 alkyl group.

In one aspect, the present invention provides a method of forming a nanotube, including: (a) adding a non-polar solvent to a plurality of amphiphilic non-chiral single-chain diacetylenic compounds (e.g., compounds having formula (I)) dissolved or suspended in a reaction solvent, e.g., dichloromethane; (b) drying the reaction solution, thereby forming a primitive structure; (c) preparing a primitive structure solution containing the primitive structure; (d) sonicating the primitive structure solution; and (e) drying the primitive structure solution, thereby forming the nanotubes. In one embodiment, the method further includes applying the primitive structure solution onto a substrate before the step (e). Examples of substrates suitable for the purpose of the present invention include, without limitation, a glass, a ceramic, a metal, a plastic, a polymer, and combinations thereof.

The non-polar solvent may be any suitable non-polar solvent known in the art, including, without limitation, hexane, heptane, cyclohexane, diethyl ether, and combinations thereof. In one embodiment, the ratio (v/v) of the non-polar solvent to the reaction solvent (e.g., dichloromethane) may be about 1:10. In another embodiment, such ratio is about 3:4. The resulting solution may be dried using standard techniques known in the art, such as, vacuum evaporation.

The primitive structure may be dissolved, completely or partially, in a solvent, such as, without limitation, water or water-based solution, dichloromethane, chloroform, carbon tetrachloride, tetrahydrofuran, ethyl acetate, N,N-dimethylformamide, acetone, alcohols, and combinations thereof, to form the primitive structure solution. As used herein and in the appended claims, the terms "solution" and "suspension" as applied to nanotube compositions includes homogenous and heterogeneous, aqueous and non-aqueous mixtures, in which a sufficient fraction of free and non-agglomerated nanotubes are present to carry out the desired transformation.

Any sonication system known in the art suitable for delivering sonic energy sufficient for the treatment of a solution may be used with the method of the present invention. Such devices may at times be referred to in the art as sonicators, ultrasonicators, sonic probes, or ultrasonic baths. A sonicator may contain a number of subsystems or affiliated systems, such as, without limitation, a programmable computerized control system and a temperature controlling system (e.g., a component which may function as a water bath). In one embodiment, a sonicator may be controlled, manually or by using a computerized control system, to operate in a continuous mode or a pulse mode. In another embodiment, for example, a sonication process may be conducted at 100 watts energy output, using continuous mode, in a water bath at room temperature. In yet another embodiment, a sonication process may be performed at any suitable frequency between about 5 kHz to 200 kHz.

The present invention provides for the dispersion of nanotubes on surfaces. Suitable surfaces include, but are not limited to, glass, ceramic, and metal surfaces, as well as polymer surfaces having suitable binding groups on the surface. Binding groups are groups capable of a binding interaction with the nanotubes, under the conditions in which the nanotubes are dispersed and attached to the surface. Suitable binding groups include, but are not limited to, hydroxyl, carboxyl, sulfhydryl, metal and silicon oxides and hydroxides, hydrocarbon, fluorocarbon, and electrically charged ionic species such as ammonium and phosphonium groups. The binding interaction may be, without limitation, hydrophobic, hydrogen-bonding, ion pairing, dipole-dipole, or covalent in nature, and will depend to a large extent on the functionality present on the exterior of the nanotubes. By way of example, a sulfhydryl group on the diacetylene precursor can be employed for covalent attachment to a gold surface, as is well-known in the art. Aluminum surfaces having an oxide coating may similarly be employed, and glass surfaces may be employed with or without surface functionalization, relying either on native SiOH groups or on introduced functional groups. Preferably the nanotubes are dissolved or suspended in a non-polar solvent and dispersed on a polar surface, and the surface is preferably glass.

In a typical example, a non-polar solvent is added to a vial containing diacetylene nanotubes and the vial is sonicated in an ultrasonic bath to detach the nanotubes from the walls of the container. Next, the liquid is transferred to a second container and fresh solvent is added followed by further sonication to disperse the nanotubes. A clean 25 mm.times.75 mm glass slide is placed in the resulting nanotube suspension to serve as a support surface, and the solution is agitated for 5 minutes to coat the glass slide with nanotubes. The nanotubes presumably attach themselves to the glass surface via electrostatic interactions between surface silicate anions and the quaternary or protonated amine in the diacetylene monomer head group, and/or by hydrogen-bonding interactions. The slide is then briefly rinsed with the same solvent and dried overnight in vacuo at room temperature.

Suitable non-polar solvents may be linear, branched, or cyclic, and include, but are not limited to, pentane, hexane, heptane, octane, isooctane, nonane, decane, cyclohexane, and the like, and mixtures thereof. Sonication is typically conducted in a water bath at room temperature. An ultrasonic bath with a power level of 100 W is suitable; the sonication method is preferably continuous rather than pulsed.

The surface-bound nanotubes are then exposed to radiation in order to initiate topochemical polymerization of the diacetylene moieties. Suitable radiation is any radiation known to induce diacetylene polymerization, and includes both UV and gamma radiation. Any UV- or gamma-radiation generating device known in the art to be suitable for polymerizing unsaturated compounds in solution may be used with the method of the present invention. The UV light may be filtered so that the device outputs UV light of a particular wavelength at a given time. In preferred embodiments, UV light having a wavelength of about 254 n1 is employed.

In another aspect, the present invention provides a method of forming a supramolecular assembly of nanotubes in the form of a "nanocarpet", including: (a) adding a non-polar solvent to an initiation solution, wherein the initiation solution contains a plurality of amphiphilic non-chiral single-chain diacetylenic compounds; (b) drying the initiation solution, thereby forming a primitive structure; (c) preparing a primitive structure solution (e.g., chloroform, dichloromethane, or carbon tetrachloride solution) containing the primitive structure; (d) sonicating the primitive structure solution; (e) treating the primitive structure solution with ultraviolet light (UV) or a .gamma.-ray irradiation; (f) partially drying the primitive structure solution, thereby forming a secondary structure; (g) adding a secondary structure solvent (such as, without limitation, chloroform, dichloromethane, carbon tetrachloride, ethyl acetate, or ethyl ether) to the secondary structure; and (h) drying the secondary structure, thereby forming the nanocarpet. In one embodiment, the method further includes applying the primitive structure solution onto a substrate (e.g., glass) before the step (f). The term "partially drying," or "partially concentrating," generally refers to a process of eliminating about 60-90% of the solvent from a solution.

In yet another aspect, the present invention provides a method of forming a nanocarpet, including: (a) partially drying/concentrating an initiation solution (e.g., without limitation, a chloroform, dichloromethane, carbon tetrachloride, or ethyl acetate solution) containing a plurality of amphiphilic non-chiral single-chain diacetylenic compounds, thereby forming a intermediate structure; (b) adding H.sub.2O or an aqueous solution to the intermediate structure; (c) treating the intermediate structure with ultraviolet light or .gamma.-ray irradiation; and (d) drying the intermediate structure, thereby forming the nanocarpet. In one embodiment, the method further includes applying the primitive structure solution onto a substrate (e.g., glass) before the step (a).

The present invention also provides a method of destroying or limiting/inhibiting the growth or proliferation of a microorganism, including contacting the microorganism with at least one nanotube which contains a plurality of amphiphilic non-chiral single-chain diacetylenic compounds (e.g., compounds of formula (I)). In one embodiment, a plurality of nanotubes may be polymerized (e.g., using UV light having a wavelength of about 254 nm) before contacting with the target microorganism. In another embodiment, the microorganism may include, without limitation, actinomycete, algae, archaeobacteria, cyanobacteria, gram-negative bacteria, gram-positive bacteria, fungi, and protozoa. In addition, the microorganism may be isolated, semi-isolated (e.g., in cell culture media), or unisolated (e.g., as a food contaminant or as a pathogen inside a subject (e.g., an animal, a human, or a plant)). Surfaces, including but not limited to the surfaces of implanted medical devices such as sutures, stents, and artificial joints and organs, may be rendered sterile and/or given microbicidal properties by coating them with the nanotubes or supramolecular assemblies of the present invention. Also provided by the invention are pharmaceutical compositions, containing a pharmaceutically-acceptable carrier and a compound of formula (I) and/or a nanotube which includes a plurality of compounds of formula (I).

The pharmaceutically-acceptable carrier may be "acceptable" in the sense of being compatible with the other ingredients of the composition, and not deleterious to the recipient thereof. The pharmaceutically-acceptable carrier employed herein may be selected from various organic or inorganic materials that are used in pharmaceutical formulations, and which may be incorporated as analgesic agents, buffers, binders, disintegrants, diluents, emulsifiers, excipients, extenders, glidants, solubilizers, stabilizers, suspending agents, tonicity agents, vehicles, and/or viscosity-increasing agents. If necessary, pharmaceutical additives, such as antioxidants, aromatics, colorants, flavor-improving agents, preservatives, and sweeteners, may also be added. Examples of acceptable pharmaceutical carriers include carboxymethyl cellulose, crystalline cellulose, glycerin, gum arabic, lactose, magnesium stearate, methyl cellulose, powders, saline, sodium alginate, sucrose, starch, talc, and water, among others.

The pharmaceutical composition of the present invention may be prepared by methods well-known in the pharmaceutical arts. For example, the composition may be brought into association with a carrier or diluent, as a suspension or solution. Optionally, one or more accessory ingredients (e.g., buffers, flavoring agents, surface active agents, and the like) also may be added. The choice of carrier will depend upon the route of administration of the composition. Formulations of the composition may be conveniently presented in unit dosage, or in such dosage forms as aerosols, capsules, elixirs, emulsions, eye drops, injections, liquid drugs, pills, powders, granules, suppositories, suspensions, syrup, tablets, or troches, which can be administered orally, topically, or by injection, including, without limitation, intravenous, intraperitoneal, subcutaneous, and intramuscular injection.

The pharmaceutical composition may be provided in an amount effective to treat a microorganism-induced disorder (e.g., an infectious disease) in a subject to whom the composition is administered. As used herein, the phrase "effective to treat the disorder" means effective to eliminate, ameliorate, or minimize the clinical impairment or symptoms resulting from the disorder.

In one embodiment of the present invention, the pharmaceutical composition may be administered to a human or animal subject by known procedures, including, without limitation, oral administration, parenteral administration (e.g., epifascial, intracapsular, intracutaneous, intradermal, intramuscular, intraorbital, intraperitoneal, intraspinal, intrasternal, intravascular, intravenous, parenchymatous, or subcutaneous administration), transdermal administration, and administration by osmotic pump.
 

Claim 1 of 16 Claims

1. A compound having formula (I): W--C.ident.C--C.ident.C--V-L-Q X (I) wherein the moiety W--C.ident.C--C.ident.C--V is a bilayer-compatible hydrophobic chain, wherein W is CH.sub.3(CH.sub.2).sub.a-- and V is --(CH.sub.2).sub.b--; where a+b is from about 4 to about 40; L is a linker comprising a chain of about 1-10 atoms; Q is --NH.sub.2R.sup.+; X is an anion; R is selected from the group consisting of C.sub.1-C.sub.8 alkyl and C.sub.6-C.sub.10 aryl; R being unsubstituted or substituted with one or more substituents selected from the group consisting of halogen, oxo, acyl, alkenyl, alkoxyl, alkyl, alkylamino, amino, aryl, cycloalkyl, heterocyclyl, and heterocyclylalkyl.

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