Polycyclic aromatic bridges for molecular electronic sensors

Patent metadata

Field	Value
Publication number	US-12504396-B2
Application number	US-202017602999-A
Country	US
Kind code	B2
Filing date	Apr 13, 2020
Priority date	Apr 12, 2019
Publication date	Dec 23, 2025
Grant date	Dec 23, 2025

Abstract

In various embodiments, synthetic bridge molecules are disclosed, usable in molecular electronics sensors. In various aspects, bridge molecules comprise fused ring polycyclic aromatic hydrocarbon structures in the shape of a long and narrow ribbon, with end groups on opposite short ends for selective binding to metal electrodes, one or more substituents near the midpoint of a long edge for binding to a probe molecule, and one or more additional substituent groups for solubility or other effects. In various embodiments, the bridge molecules herein are conducting, and provide a closed circuit in a sensor when forming a bridge between gapped electrodes.

First claim

We claim:

1 . A synthetic bridge molecule for use in a molecular electronics sensor, the molecule comprising the structure:

wherein:
n and m are independently 0 to 30;
W and Y are independently selected from —O—, —CH2-, CR 8 R 9 , CH 2 CR 8 R 9 , CR 8 CR 9 CH 2 , OCR 8 R 9 and CR 8 R 9 O, wherein R 8 and R 9 are attached to the same carbon atom and independently selected from H, CH 3 , C 2 H 5 , CH 2 CH 2 CH 3 , or (CH 2 ) X (OCH 2 CH 2 ) Y OR 10 , wherein x is 2 to 10, y is 10 to 40 and R 10 is H, Me, or Et, and wherein R 8 and R 9 can optionally link to form a ring, wherein O is optionally linked directly to the aromatic ring, and wherein W and Y can optionally be exchanged with one another within a ring;
W′ and Y′ are independently selected from —O—, —CH2-, CR 8 R 9 CH2CR 8 R 9 , CR 8 CR 9 CH2, OCR 8 R 9 , and CR 8 R 9 O, wherein R 8 and R 9 are attached to the same carbon atom and independently selected from H, CH 3 , C 2 H 5 , CH 2 CH 2 CH 3 , or (CH 2 ) X (OCH 2 CH 2 ) Y OR 10 , wherein x is 2 to 10, y is 10 to 40 and R 10 is H, Me, or Et, and wherein R 8 and R 9 can optionally link to form a ring, wherein O is optionally linked directly to the aromatic ring, and wherein W′ and Y′ can optionally be exchanged with one another within a ring;
R 1 is a moiety selected from (i) ester linked PEG chains (CH 2 ) x CO(OCH 2 CH 2 ) y OR 13 or CH 2 ) x OC═OCH 2 CH 2 CH 2 (OCH 2 CH 2 ) y OR 13 , wherein x is from 0 to 10, y is from 10 to 40, and R 13 is Me or H; or (ii) a water-soluble, ester-linked dendron comprising 8 to 64 branches, each derivatized with water-solubilizing PEG chains of structure (CH2CH 2 O) z R 14 wherein z is from 1 to 8 and R 14 is H or Me, wherein the ester-linkage of R 1 optionally comprises a 1) photocleavable, 2) redox-cleavable, 3) acid cleavable or 4) base-cleavable linker such that the dendron can be removed using 1) light, 2) an oxidizing or reducing agent, 3) an acid or 4) a base, respectively;
R 2 s a moiety selected from (i) ester linked PEG chains (CH 2 ) x CO(OCH 2 CH 2 ) y OR 13 or (CH 2 ) x OC═OCH 2 CH 2 CH 2 (OCH 2 CH 2 ) y OR 13 wherein x is from 0 to 10, y is from 10 to 40, and R 13 is Me or H, ii) a water-soluble, ester-linked dendron linked from the nanoribbon with 4 to 16 branches, each devitalized with water-solubilizing PEG chains (CH 2 CH 2 O) z R 14 wherein z is from 1 to 4 and R 14 is H or Me, wherein the ester-linkage of R 2 optionally comprises a 1) photocleavable, 2) redox-cleavable, 3) acid cleavable or 4) base-cleavable linker such that the dendron can be removed using 1) light, 2) an oxidizing or reducing agent, 3) an acid or 4) a base, respectively;
W″ and Y″ are independently selected from —S—, —CH 2 —, CH 2 CH 2 , CR 11 R 12 , and SCR 11 R 12 , wherein R 11 and R 12 are bonded to the same carbon atom and independently selected from H, CH 3 , C 2 H 5 , CH 2 CH 2 CH 3 , CH 2 CH 2 SCH 3 , SCH 3 , or SCH 2 CH 2 SCH 3 , and wherein R 8 and R 9 can optionally link to form a ring, wherein S is optionally linked directly to the aromatic ring, and wherein W″ and Y″ can optionally be exchanged with one another within a ring;
R 5 is H, SMe, or CH 2 CH 2 SMe;
R 6 is H, SMe, SCH 2 CH 2 SMe, SCH 2 C(CH 2 SMe) 3 , SH, CS 2 H, CH 2 SMe, CH 2 SH, CH 2 CS 2 H, 6[1,3-diisopropyl-1H-benzo[d]imidazol-3-ium]-yl or 6-[1,3-diisopropyl-1H-benzo[d]imidazol-3-ium]-thioyl; and
R 7 is H, SMe, SCH 2 CH 2 SMe, SH, CS 2 H, CH 2 SMe, CH 2 SH, CH 2 CS 2 H, 6-[1,3-diisopropyl-1H-benzo[d]imidazol-3-ium]-yl or 6-[1,3-diisopropyl-1H-benzo[d]imidazol-3-ium]-thioyl.

2 . The synthetic bridge molecule of claim 1 , wherein:
m+n=10 to 24; Y═W═—CH 2 — or —O—; Y′═W′═—CH 2 — or —O—; Y″═W″═—S—; R 1 ═—CO—O—(CH 2 CH 2 O)n-OCH 3 , wherein n is between 2 and 7 or between 20 and 48; R 2 ═—CO—O—(CH 2 CH 2 O) n —OCH 3 , wherein n is between 2 and 7 or between 20 and 48; R 3 ═(L-Phe-Gly) 4 -NHOCH 2 CH 2 O—N═CH(p-C 6 H 4 )CH 2 —; R 4 ═H; R 5 ═CH 2 CH 2 SMe; R 6 ═SCH 2 CH 2 SMe; and R 7 ═H.

3 . The synthetic bridge molecule of claim 2 , wherein:
R 1 ═PEG-20; Y and W are —O—; R 3 =azido-(CH 2 ) 10 ; R 4 =biotin-PEG-5; R 5 ═H; R 6 =methylthiol, and R 7 ═H.

4 . The synthetic bridge molecule of claim 1 , wherein:
m+n=10 to 24; Y═W═—CH 2 — or —O—; Y′═W′═—CH 2 — or —O—; Y″═W″═—S—; R 1 ═H; R 2 ═—CO—O—(CH 2 CH 2 O) n —OCH 3 , wherein n is between 2 and 7 or between 20 and 48; R 3 ═ —(CH 2 ) n C(O)NH—CH[(CH 2 ) r (CH 2 )R 18 ][CH 2 CH 2 —O—CH 2 CH 2 O—(CH 2 ) s R 19 , wherein n, r and s are independently between 2 and 7; and wherein R 18 and R 19 are independently selected from —N 3 , —CC—H, —NHCO-biotin, —CHO, —COCH 3 and —O—NH 2 , with the proviso that R 18 and R 19 cannot react with one another; R 4 ═R 5 ═p- or m-(C 6 H 4 )—(CH 2 ) t COO(CH 2 CH 2 O) u CH 3 , wherein t is from 0) to 10 and u is from 5 to 50; R 6 ═SCH 2 CH 2 SMe; and R 7 ═H.

5 . A synthetic bridge molecule according to claim 1 , comprising the structure

wherein:
n=2;
m=3 to 500;
R 1 is selected from: (1) an ester linked PEO chain having the structure (CH 2 ) x CO(OCH 2 CH 2 ) y OR 13 or (CH 2 ) x OC═OCH 2 CH 2 CH 2 (OCH 2 CH 2 ) y OR 13 ; wherein x is from 3 to 10, y is from 10 to 40, and R 13 is Me or H; (2) an ether linked PEG chain having the structure (CH 2 )O—CH 2 CH 2 CH 2 (OCH 2 CH 2 ) y OR 13 , wherein x>2, y is from 10 to 40, and R 13 is Me or H; or (3) water-soluble ester-linked dendron, comprising 8 to 64 branches, each derivatized with water-solubilizing PEG chains (CH 2 CH 2 O) z R 14 , wherein z is from 1 to 8 and R 14 is H or Me, and wherein the ester-linkage of R 1 can optionally include a 1) photocleavable, 2) redox-cleavable, 3) acid cleavable or 4) base-cleavable linker so that the dendron can be removed using 1) light, 2) an oxidizing or reducing agent, 3) an acid or 4) a base, respectively, after the cap portion of the molecule is linked to gold electrodes;
R 2 is selected from: (1) an ester linked PEG chain having structure (CH 2 ) x CO(OCH 2 CH 2 ) y OR 13 or (CH 2 ) x OC═OCH 2 CH 2 CH 2 (OCH 2 CH 2 ) y OR 13 , wherein x is from 3 to 10, y is from 10 to 40, and R 13 is Me or H; (2) an ether linked PEG chain having the structure (CH 2 ) x O—CH 2 CH 2 CH 2 (OCH 2 CH 2 ) y OR 13 , wherein x>2, y is from 10 to 40, and R 13 is Me or H or (3) —H;
R 3 ═—(CH 2 ) n C(O)NH—CH[(CH 2 ) r (CH 2 )R 18 ][CH 2 CH 2 —O—CH 2 CH 2 O—(CH 2 ) s R 19 ,

wherein n, r and s are independently between 2 and 7; and wherein R 18 and R 19 are independently selected from —N 3 , —CC—H, —NHCO-biotin, —CHO, —COCH 3 and —O—NH2, with the proviso that R18 AND R19 cannot react with one another;
R4 is H or SCH 2 CH 2 SCH 3 ; and
R5 is —SH or SCH 2 CH 2 SCH 3 .

6 . A synthetic bridge molecule according to claim 1 , the molecule comprising the structure,

wherein:
n and m are independently 0 to 30;
R 1 ═R 2 ═—(CH 2 ) 4 C(O)O-PEG-48;
R- 3 ═H or —NR 9 R 10 wherein R 9 is linked to a DNA polymerase cysteine residue and R 10 is either H or R 10 forms a ring with R 9 that does not include the polymerase, or R 10 is linked to a DNA polymerase cysteine residue that is distinct from the residue linked to R 9 ;
R 4 ═R 5 ═H
R 6 ═CH 2 SCH 2 CH 2 SCH 3 or H,
R 7 ═CH 2 SCH 2 CH 2 SCH 3 or H; and
R 8 ═CH 2 SCH 2 CH 2 SCH 3 or —SH.

7 . The sy

Assignees

• Roswell Biotechnologies Inc
• SemiconBio

Inventors

• Merriman Barry
• Geiser Tim
• Mola Paul W
• Rideout Darryl

Classifications

• G01N27/307

  Disposable laminated or multilayered electrodes (G01N27/3272 takes precedence) · CPC title

• C08F136/22

  the radical having three or more carbon-to-carbon double bonds · CPC title

• C07D495/04

  Ortho-condensed systems · CPC title

• C07C2603/54

  containing more than five condensed rings · CPC title

• C07C321/24

  Thiols, sulfides, hydropolysulfides, or polysulfides having thio groups bound to carbon atoms of six-membered aromatic rings · CPC title