CA-3036495-C - OXIDATION CATALYSTS BASED ON MACROCYCLIC COMPOUNDS

Abstract

In a preferred embodiment, there is provided a compound comprising a macrocyclic tetradentate ligand of the structure (see structure above) wherein D is a nitrogen atom; each X is (i) H, deuterium, (ii) Li, Na, K, alkali metals, (iii) alkaline earth metals, transition metals, rare earth metals, (iv) or is unoccupied with the resulting negative charge being balanced by a nonbonded countercation; and Y1, Y2, Y3 and Y4 are each independently selected from the group consisting of (see chemical compounds 1, 2, 3 and 4) wherein every D is directly attached to at least one E, and E is S(=Q)2, S(=Q)R'2, S(=Q), P(=Q)R', PR'3 or C=Q, where Q is oxygen or NR', wherein at least one E in at least one Y is more stable towards nucleophilic attack than C=Q and is S(=Q)2, S(=Q)R'2, or S(=Q), and is directly attached to one D.

Inventors

• Terrence James Collins
• Matthew Alan DeNardo
• Genoa Rose Warner
• Scott Wallace Gordon-Wylie
• William Chadwick Ellis
• Yogesh Somasundar

Assignees

• CARNEGIE MELLON UNIVERSITY

Dates

Publication Date

20260505

Application Date

20160922

Priority Date

20150925

Claims (14)

1. 98 We claim: 1. A compound characterized by any of the following formulas: or wherein 99 R1 and R2 are each independently selected from hydrogen, deuterium, alkyl, aryl, halogen, haloalkyl, perhaloalkyl, haloaryl, perhaloaryl, nitrile, nitro, hydroxyl, alkoxy, aryloxy, an unsubstituted cycloalkyl ring, an unsubstituted cycloalkenyl ring, an unsubstituted saturated heterocyclic ring, and an unsubstituted unsaturated heterocyclic ring, or which forms, together with the carbon atom to which both are bound, an unsubstituted three-, four-, five- or six-membered ring; G is independently selected from halogen, hydrogen, alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, aryl, polycyclic aryl which optionally contain at least one ring atom that is not carbon, alkylaryl, phenoxy, amino, carboxylic acid, esters, amides, sulfonates, sulfones, sulfonamides, phosphates, phosphonates, phosphinate, phosphine oxide, phosphonamides, phosphines, nitrile, nitro, hydroxyl, alkoxy, aryloxyn and siloxy; and R' is independently selected from H, deuterium, Li, Na, K, alkaline earth metals, transition metals, rare earth metals, alkyl, alkenyl, alkynyl, aryl, alkoxy, phenoxy, halogenated alkyl, halogenated aryl, halogenated alkenyl, halogenated alkynyl, perhaloalkyl, perhaloaryl, an unsubstituted cycloalkyl ring, an unsubstituted cycloalkenyl ring, an unsubstituted saturated heterocyclic ring containing oxygen, and an unsubstituted unsaturated heterocyclic ring.
2. 2. A chelate complex comprising a compound according to claim 1 and a metal.
3. 3. The complex of claim 2 wherein the metal is a transition metal.
4. 4. The complex of claim 3 wherein the metal is Fe or Mn.
5. 5. A process for preparing the compound of claim 1, in which two α- or βactivated amino acid derivatives, having parent, hidden/activated, and protected functionalities, which are the same or different, are selectively coupled to a diamine in the presence of a solvent and base, the protected or hidden amine functionalities converted to a primary amine, and the resulting diamine intermediate coupled with an activated diacid linker in the presence of a solvent and a base.
6. 6. A process for preparing the chelate complex of claim 2 comprising adding a metal complex to the compound of claim 1 under basic conditions. 100
7. 7. The ex vivo use of the complex of any one of claims 2 to 4 in the presence of an oxidant for performing a catalytic oxidation reaction upon a target.
8. 8. The ex vivo use of claim 7, wherein the complex is added for activation of the oxidant against any target that is oxidizable in water.
9. 9. The ex vivo use of claim 7, wherein the complex is added for activation of the oxidant against any target that is a micropollutant.
10. 10. The ex vivo use of claim 7, wherein the complex is added for activation of the oxidant for disinfection, sterilization, fungicidal, algaecidal, bactericidal, insecticidal and herbicidal oxidations, or for water treatment.
11. 11. The complex of any one of claims 2 to 4 for use in wound cleaning, disinfection, sterilization, fungicidal, algaecidal, bactericidal, or insecticidal treatment in the presence of an oxidant for performing a catalytic oxidation reaction upon a target.
12. 12. The use of claim 7 or the complex for use of claim 11, wherein the complex is present in substoichiometric or stoichiometric quantities compared to the target, or in excess compared to the target.
13. 13. The use of claim 7 or the complex for use of claim 11, wherein the oxidant is selected from the group consisting of halogen, halogen oxide, halogenoxoanion, elemental halogen, a peroxy compound, hydrogen peroxide, oxygen, air, ozone, oxygen in the presence of an adjunct, an electrode with or without a mediating compound that is regenerated by an electrode; elemental chlorine, chlorine oxide, chlorine oxoanion, chlorine dioxide, hypochlorite, acidic species thereof and combinations thereof.
14. 14. A process for the generation of O2 applying water or any other source of oxygen to the complex of claim 2, and applying energy thereto.

Description

OXIDATION CATALYSTS BASED ON MACROCYCLIC COMPOUNDS FIELD OF THE INVENTION This invention relates to metal chelate complexes for serving as oxidation catalysts, and more particularly, to the design of macrocyclic catalytic activators of common oxidizing agents that far outperform the previous leaders in this technology space, namely "T AML Activators." BACKGROUND Macrocyclic tetradentate ligand metal complex activators, invented at Carnegie Mellon University and sold commercially as TAML® activators, are longlived, fully functional mimics of the great families of oxidizing enzymes, namely the peroxidase enzymes (See U.S. Patents Nos. 5,847,120; 5,853,428; 5,876,625; 6,054,580; 6,051,704; 6,099,586; 6,011,15_2; 6,100,394; 6,136,223; 6,241,779, and 6,992,184, collectively, the "Collins' Group Patents,"). For many years, the studies to make ever more robust TAML® catalysts followed the same design hypothesis that led to TAML® activators in the first place; that the functioning catalysts were being inactivated by oxidative degradation of the most vulnerable site in the macrocyclic ligand systems and that by finding and strengthening the most oxidatively vulnerable site, a superior catalyst would be produced. At the same time as that iterative design process was being followed to improve the performance ofTAML® catalysts, the mechanisms ofTAML® catalyst behavior were studied and a set of Technical Performance Parameters (referred to herein as "Techperps") was developed that eventually cast doubt on the original design hypothesis for certain applications. While TAML activators remain impressive catalysts for the activation of numerous oxidizing agents and work well enough to allow, for example, micropollutants (MPs, a term for any pollutant that has an adverse effect at very small concentrations, typically in the range of parts per trillion to low parts per billion) to be degraded in water with catalyst concentrations in the low nanomolar regime (::580 nM), it was found that the • I I I macrocyclic tetraamido ligand catalysts run into a stability wall of non-oxidative decay that cannot be escaped. BRIEF SUMMARY OF THE INVENTION T AML activators are iteratively invented oxidation catalysts that advanced based on ' 5 the hypothesis that catalyst lifetimes were limited by destructive oxidation processes caused by the aggressive oxidizing conditions of functioning TAML processes. Over more than a decade of following this hypothe~is, we were unable to rationalize a stability wall and thus were unable to find iterative design steps that could break through it. The present inventions arise from a discovery of the fact that our fundamental hypothesis was wrong. The 1 0 overarching challenge solved by the inventions of this patent has been to achieve new composition of matter catalyst systems that escape the discovered non-oxidative decomposition processes, the nature of which was previously unknown. The desired ligands and derivative far superior catalyst performances are met by the macrocyclic tetradentate compounds described herein. The compounds have the general structure (Compound 1) wherein: D is an N donor atom; and each X is a position for addition ofa labile Lewis acidic substituent such as (i) H, deuterium, (ii) Li, Na, K, other alkali me~s, or (iii) alkaline earth metals, transition metals, rare earth metals, which may be bound to one or more than one D, or (iv) is unoccupied with the resulting negative charge being balanced by a nonbonded countercation. As used in Compound 1, Y1, Y2, Y3 and Y4 are each independently selected from the 2 5 group consisting of 2 E-E I \ XR1 R2 Ra [is '\ E E S' Aslt,,,,,c/ 'E / ............ • ...... Rs E C E E \ I \ I \ I H H Rs Ra H z z ~ E/ 'e E/ 'c~Rs Rs11', ,,..C/ z ........._E \ I \ I \ I zA' Rz' Rs As R' ~ Rs11,,~/ 2 E/ '--E E/ '--c~Ra '--e \ I \ I \ I R'1 R'2 A'1 A'2 R'1 R'2 \z/ \ z/ ~Rs Rs \I ~ E/+ .......... E E/ +'--.c·. ..... Ra Rs"'' "··c/ z• ""-e \ I \ I \ I wherein: Eis selected from the groups consisting of S(=Q)2, S(=Q)R'2, S(=Q), P(=Q)R', PR'3 and C=Q, where Q is oxygen or ZR', wherein at least one E in at least one Y is more stable 5 towards nucleophilic attack than C=Q and is selected from the group consisting of S(=Q)2, S(=Q)R' 2, S(=Q), P(=Q)R' or PR' 3 and is directly attached to one D in said Compound 1; Z is selected from the group consisting of 0, S (where there may or may not be an R' or H substituent), N, P, and As (where for N, P, and As one or two R's, designated R' 1 and R' 2, may be present); and 10 R' is selected from the group consisting of (i) H, deuterium, (ii) Li, Na, K, other alkali metals, (iii) alkaline earth metals, transition metals, rare earth metals, (iv) oxygen, hydroxyl, halogen, a nitrogen-containing group, a carbon-containing group selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, alkoxy, phenoxy, halogenated alkyl, halogenated aryl, halogenated alkenyl, halogenated alkynyl, perhaloalkyl, perhaloaryl, a substituted o