# US 9,518,067 B2 · Trifluoroborate mass spectrometric tags

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 9,518,067 B2
- Document ID: US9518067B2
- Status: Granted
- Kind: B2
- Application number: 15/136,920
- Filed: 2016-04-23
- Published: 2016-11-17
- Granted: 2016-12-13
- Earliest claimed: 2013-03-27
- Assignees: CellMosaic, Inc.
- Applicants: CellMosaic, inc.
- Inventors: Yumei Huang
- Web page: https://patentgrep.com/patent/US9518067B2

## CPC

- C07F 5/02: Boron compounds
- C07F 5/025: {Boronic and borinic acid compounds}
- C08G 65/34: from hydroxy compounds or their metallic derivatives {(C08G65/26 takes precedence)}
- C08G 65/48: Polymers modified by chemical after-treatment
- G01N 27/62: by investigating the ionisation of gases, e.g. aerosols; by investigating electric discharges, e.g. emission of cathode
- H01J 49/0027: {Methods for using particle spectrometers}
- H01J 49/02: Details
- C08G 2650/04: End-capping
- C08G 2650/48: containing fluorine, e.g. perfluropolyethers
- C07F: ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM (metal-containing porphyrins C07D487/22)
- C08G: MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)
- H01J: ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS (spark-gaps H01T; electric arc lamps H05B31/00; particle accelerators H05H)

## Abstract

The invention provides compositions and methods for mass spectrometric (MS), organic synthesis, and applications of organo-trifluoroborate, for example, as mass tags for use in negative ion mode. When subject to MS fragmentation, organo-trifluoroborates preferentially undergo neutral losses of hydrogen fluoride (HF) or boron trifluoride (BF3) molecules, transferring the negative charge to the rest of the molecule. Such a fragmentation pattern is used to detect and quantitate analytes of interest after derivatization with organo-trifluoroborates.

## Claims

### Claim 1

An organo-bis-trifluoroborate compound having structural formula:
wherein
Y2 is a functional group selected from the group consisting of an alcohol, alkoxy, aryloxy, diene, dienophile, carboxylic acid, amine, thiol, alkyl halide, ketone, aldehyde, aminooxy, hydrazine and its derivatives, activated ester, acid halide, isocyanate or thio-isocyanate, azo, alkyne, 1,3-dipolariphile, sulfonyl chloride, glyoxal, epoxide or oxirane, carbonate, aryl halide such as fluorobenzene derivatives, imidoester or imidate, anhydride, fluorophenyl ester, hydroxymethyl phosphine derivative, maleimide, aziridine, acryloyl derivative, arylating agent such as derviatives of benzene that possess either halogen or sulfonate groups on the ring, thiol-disulfide exchange reagent such as pyridyldithiol and thiolnitrobenzoic acid, or vinylsulfone group;
L2 is a linker or a combination of 2 to 4 linkers that are independently selected from the group consisting of C1-C20
alkyl, —(CH2CH2O)1-36—, —(CH2CH2O)1-36—CH2—, a peptide, a peptidomimetic oligomer, alicyclyl, optionally substituted alicyclyl, heteroalicyclyl, optionally substituted heteroalicyclyl, and optionally substituted aryl; and
X⊕ is any positively charged counter ion.

### Claim 2 (depends on 1)

The organo-trifluoroborate compound of claim 1, wherein the organo-trifluoroborate compound labeled with one or more stable heavy isotopes selected from 10B and 11B, 12C and 13C, 14N and 15N, 16O and 18O, 1H and 2H isotopes at select atomic sites such that the total additional mass due to heavy isotope labeling is distributed between the reactive group, the linker, and trifluoroborate moiety to produce a set of isobaric and mass differential tags.

### Claim 3 (depends on 1)

The organo-trifluoroborate compound of claim 1, wherein Y2 is an aminooxy (—ONH2).

### Claim 4 (depends on 1)

The organo-trifluoroborate compound of claim 1, having structural formula:
wherein R11 and R12 is independently selected from a group consisting of H and alkoxy.

### Claim 5 (depends on 4)

The organo-trifluoroborate compound of claim 4, wherein Y2 is an aminooxy (—ONH2).

### Claim 6 (depends on 4)

The organo-trifluoroborate compound of claim 4, wherein Y2 is an amine.

### Claim 7 (depends on 5)

The organo-trifluoroborate compound of claim 5, wherein each of R11 and R12 is H.

### Claim 8 (depends on 1)

The organo-trifluoroborate compound of claim 1, having structural formula:

### Claim 9 (depends on 1)

The organo-trifluoroborate compound of claim 1, wherein X⊕ is selected from the group consisting of K+, Cs+, Rb+, quaternary ammonium, pyridinium, pyrazolium, thiazolium, morpholium, triazolium, imidazolium, bezoxazolium, thiadiazolium, oxadiazolium and guanidinium ions.

### Claim 10 (depends on 9)

The organo-trifluoroborate compound of claim 9, wherein X⊕ is K+.

### Claim 11

A kit comprising one or more organo-trifluoroborates or organo-multi-trifluoroborate mass tags.

### Claim 12 (depends on 11)

The kit of claim 11, further comprising one or more of calibrants, internal standards, biological matrices and standards, solvents, tubes and vials, separation media, capture media or agents, enrichment media or reagents, precipitating reagents, salts and buffers, system qualifying solutions, quality control samples, pH adjusting and other necessary reagents.

### Claim 13 (depends on 6)

The organo-trifluoroborate compound of claim 6, wherein each of R11 and R12 is H.