MOLECULAR CONTAINERS AND METHODS OF MAKING AND USING SAME

1 . A method of making a compound having the following structure:

a salt, a partial salt, a hydrate, a polymorph or a mixture thereof, or a stereoisomer or a mixture thereof, wherein each R is independently hydrogen, C 1 to C 20 alkyl group, C 3 to C 20 carbocyclic group, C 1 to C 20 heterocyclic group, carboxylic acid group, ester group, amide group, hydroxy, or ether group; and wherein, optionally, adjacent R groups form a C 3 to C 20 carbocyclic ring or heterocyclic ring; wherein each

is independently a C 5 to C 20 carbocyclic ring system or C 2 to C 20 heterocyclic ring system, wherein the ring system comprises one or more rings; wherein at least one ring system has at least one solubilizing group selected from sulfonic acid group, sulfonate salt group, phosphonic acid group, phosphonate salt group, and polyethylene glycol group; and wherein, optionally, the ring system has a targeting group; and wherein n is 1 to 5, the method comprising:

forming a first reaction mixture comprising:

a first compound having the following structure:

wherein m is 0 to 4 and each R 1 is independently hydrogen, C 1 to C 20 alkyl group, C 3 to C 20 carbocyclic group, C 1 to C 20 heterocyclic group, carboxylic acid group, ester group, amide group, hydroxy, or ether group; and wherein, optionally, adjacent R groups form a C 3 to C 20 carbocyclic ring or heterocyclic ring;

a second compound having the following structure:

wherein each R 2 is independently hydrogen, C 1 to C 20 alkyl group, C 3 to C 20 carbocyclic group, C 1 to C 20 heterocyclic group, carboxylic acid group, ester group, amide group, hydroxy, or ether group; wherein, optionally, adjacent R groups form a C 3 to C 20 carbocyclic ring or heterocyclic ring; and wherein Y is independently an oxygen or a nitrogen substituted with a C 1 to C 20 alkyl group; and

an acid;

holding the first reaction mixture, wherein a first compound having the following structure is formed:

wherein R is independently hydrogen, C 1 to C 20 alkyl group, C 3 to C 20 carbocyclic group, C 1 to C 20 heterocyclic group, carboxylic acid group, ester group, amide group, hydroxy, or ether group; wherein, optionally, adjacent R groups form a C 3 to C 20 carbocyclic ring or heterocyclic ring; and wherein n is 1 to 5,

forming a second reaction mixture comprising:

the first compound;

one or more third compound(s), each third compound independently having a C 5 to C 20 carbocyclic ring system or C 2 to C 20 heterocyclic ring system, wherein the ring system comprises one or more rings; wherein at least one ring system has at least one solubilizing group selected from sulfonic acid group, sulfonate salt group, phosphonic acid group, phosphonate salt group, and polyethylene glycol group; wherein, optionally, the ring system has a targeting group; and

trifluoroacetic acid; and

holding the second reaction mixture,

wherein the compound, the salt, the partial salt, the hydrate, the polymorph or the mixture thereof, or the stereoisomer or the mixture thereof is formed.

2 . The method of claim 1 , wherein the second reaction mixture comprises a single third compound.

3 . The method of claim 1 , wherein at least two or more of the third compounds are structurally distinct.

4 . The method of claim 1 , the method further comprising isolating the compound, the salt, the partial salt, the hydrate, the polymorph or the mixture thereof, or the stereoisomer or the mixture thereof.

5 . The method of claim 1 , the method further comprising derivatizing the compound of claim 1 with a solubilizing group and/or a targeting group.

6 . The method of claim 5 , wherein the compound is isolated and the derivatizing is carried out after isolating the compound.

7 . The method of claim 1 , the method further comprising adding a pharmaceutical agent to the second reaction mixture after addition of the third compound(s), wherein a pharmaceutical inclusion complex with the compound is formed.

8 . The method of claim 1 , wherein the compound is isolated, the method further comprising forming a third reaction mixture comprising the isolated compound and a pharmaceutical agent, wherein an inclusion complex with the compound is formed.

9 . The method of claim 8 , wherein the third reaction mixture is an aqueous mixture of the isolated compound and the pharmaceutical agent.

10 . The method of claim 1 , wherein the compound has one of the following structures:

wherein each i is 1 to 20;

X is the solubilizing group; and

Z is a PEG group having a molecular weight of 200 to 10,000.

11 . The method of claim 1 , wherein the compound has one of the following structures:

wherein A + is H + , Na + , K + , Ca 2+ , Mg 2+ , Zn 2+ , H 4 N + , Et 3 NH + , Me 4 N + , (HOCH 2 CH 2 ) 3 NH 30 , or a cationic form of ethylenediamine, piperazine, and trishydroxymethyl aminomethane (TRIS).

12 . A compound having the following structure:

or a salt, a partial salt, a hydrate, a polymorph or a mixture thereof, or a stereoisomer or a mixture thereof,

wherein each R is independently hydrogen, C 1 to C 20 alkyl group, C 3 to C 20 carbocyclic group, C 1 to C 20 heterocyclic group, carboxylic acid group, ester group, amide group, hydroxy, or ether group;

wherein, optionally, adjacent R groups form a C 3 to C 20 carbocyclic ring or heterocyclic ring;

wherein each

is independently a C 5 to C 20 carbocyclic ring system or C 2 to C 20 heterocyclic ring system, wherein the ring system comprises one or more rings;

wherein at least one ring system has at least one solubilizing group selected from sulfonic acid group, sulfonate salt group, phosphonic acid group, phosphonate salt group, and polyethylene glycol group;

wherein, optionally, the ring system has a targeting group; and

wherein n is 1 to 5.

13 . The compound of claim 12 , wherein each

is independently a C 5 to C 20 carbocyclic ring having one of the following structures:

wherein at each occurrence of

R 1 to R 16 is independently hydrogen, C 1 to C 20 alkyl group, halo group, hydroxyl group, nitro group, carboxylic acid group, ester group, amide group, ether group, C 3 to C 20 carbocyclic group, or C 1 to C 20 heterocyclic group, provided that at least one of R 1 to R 16 in the compound has the following structure:

wherein LG is a linking group and X is the solubilizing group; and

wherein optionally one or more adjacent R 1 to R 16 groups are connected forming a carbocyclic ring or heterocyclic ring.

14 . The compound of claim 13 , wherein

has the following structure:

wherein each i is 1 to 20.

15 . The compound of claim 13 , wherein at least one of the R 1 to R 16 groups in the structure has the following structure:

and wherein LG is a linking group and wherein TG is the targeting group.

16 . The compound of claim 12 , wherein the

groups are the same.

17 . The compound of claim 14 , wherein the compound has one of the following structures:

wherein Z is a PEG group having a molecular weight of 200 to 10,000.

18 . The compound of claim 13 , wherein the compound has one of the following structures:

wherein A + is H + , Na + , K + , Ca 2+ , Mg 2+ , Zn 2+ , H 4 N + , Et 3 NH + , Me 4 N + , (HOCH 2 CH 2 ) 3 NH 30 , or a cationic form of ethylenediamine, piperazine, and trishydroxymethyl aminomethane (TRIS).

19 . A method for reversing an effect of an agent used in anesthesia, the method comprising administering to an individual an effective amount of a compound having the following structure:

or a salt, a partial salt, a hydrate, a polymorph or a mixture thereof, or a stereoisomer or a mixture thereof,

wherein each R is independently hydrogen, C 1 to C 20 alkyl group, C 3 to C 20 carbocyclic group, C 1 to C 20 heterocyclic group, carboxylic acid group, ester group, amide group, hydroxy, or ether group; and

wherein, optionally, adjacent R groups form a C 3 to C 20 carbocyclic ring or heterocyclic ring;

wherein each

is independently a C 5 to C 20 carbocyclic ring system or C 2 to C 20 heterocyclic ring system, wherein the ring system comprises one or more rings;

wherein at least one ring system has at least one solubilizing group selected from sulfonic acid group, sulfonate salt group, phosphonic acid group, phosphonate salt group, and polyethylene glycol group;

wherein, optionally, the ring system has a targeting group; and

wherein n is 1 to 5,

and wherein subsequent to the administration the effect of the agent is reversed.

20 . The method of claim 19 , wherein the compound is present in a pharmaceutical formulation when administered to the individual.

21 . The method of claim 20 , wherein the individual is a human.

22 . The method of claim 21 , wherein the agent is a neuromuscular blocking agent.

23 . The method of claim 22 , wherein the neuromuscular blocking agent is Rocuronium.