Polycations and methods of making and using thereof
Disclosed are polycationic polymers. The polycationic polymers can include a plurality of positively charged centers, each of which is formed by condensation of cyclic bis-electrophile (e.g., a 9-thia/aza/selenabicyclo[3.3.1]nonyl electrophile) with a nucleophile. The resulting polycationic polymers can efficiently bind nucleic acids. The polycations can also exhibit properties of cytotoxicity and DNA transfection with interesting structure-activity characteristics.
1. A polycationic polymer derived from the condensation of a cyclic bis-electrophile, a first polynucleophilic monomer, and a second polynucleophilic monomer,
wherein the cyclic bis-electrophile is defined by Formula II below
wherein
each dotted line represents a cyclic moiety;
LG represents a leaving group;
Z represents S, Se, or NR 3 ; and
R 3 represents alkyl, alkenyl, alkynyl, alkoxy, aryl, heteroaryl, alkylaryl, alkylheteroaryl, cycloalkyl alkylcycloalkyl, heterocycloalkyl, alkylheterocycloalkyl, peptidyl, polyamino, or polyalkyleneoxy;
wherein the first polynucleophilic monomer is defined by Formula III below
wherein
A represents a heterocyclic ring comprising a tertiary nitrogen atom;
Y is absent or represents a linking group; and
R 1 is absent, or represents halogen, hydroxy, amino, cyano, azido, hydrazone, alkyl, alkenyl, alkynyl, alkoxy, aryl, heteroaryl, alkylaryl, alkylheteroaryl, cycloalkyl alkylcycloalkyl, heterocycloalkyl, alkylheterocycloalkyl, alkylthio, alkylsulfinyl, alkylsulfonyl, alkylamino, dialkylamino, alkylcarbonyl, alkoxycarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, peptidyl, polyamino, or polyalkyleneoxy; and
wherein the second polynucleophilic monomer is defined by Formula IV below
wherein
A represents a heterocyclic ring comprising a tertiary nitrogen atom;
Y is absent or represents a linking group; and
R 1 is absent, or represents halogen, hydroxy, amino, cyano, azido, hydrazone, alkyl, alkenyl, alkynyl, alkoxy, aryl, heteroaryl, alkylaryl, alkylheteroaryl, cycloalkyl alkylcycloalkyl, heterocycloalkyl, alkylheterocycloalkyl, alkylthio, alkylsulfinyl, alkylsulfonyl, alkylamino, dialkylamino, alkylcarbonyl, alkoxycarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, peptidyl, polyamino, or polyalkyleneoxy.
2. The polycationic polymer of claim 1 , wherein the cyclic bis-electrophile is defined by Formula IIA, Formula IIB, or Formula IIC below
wherein LG and Z are as defined above with respect to Formula II.
3. A polycationic polymer comprising a recurring unit defined by Formula V below
wherein
R 4 represents H or methyl;
L is absent or represents a linking group;
A represents, individually for each occurrence, a heterocyclic ring comprising a cationic nitrogen center;
R 5 is absent, or represents, individually for each occurrence, halogen, hydroxy, amino, cyano, azido, hydrazone, alkyl, alkenyl, alkynyl, alkoxy, aryl, heteroaryl, alkylaryl, alkylheteroaryl, cycloalkyl alkylcycloalkyl, heterocycloalkyl, alkylheterocycloalkyl, alkylthio, alkylsulfinyl, alkyl sulfonyl, alkylamino, dialkylamino, alkylcarbonyl, alkoxycarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, peptidyl, polyamino, or polyalkyleneoxy; and
m is an integer from 0 to 5.
4. The polycationic polymer of claim 3 , wherein the polycationic polymer further comprises a recurring unit derived from the polymerization of one or more ethylenically-unsaturated monomers.
5. The polycationic polymer of claim 4 , wherein the one or more ethylenically-unsaturated monomers are chosen from the group consisting of styrene, butadiene, meth(acrylate) monomers, vinyl acetate, vinyl ester monomers and combinations thereof.