Xanthylium dyes that are well retained in mitochondria
AssigneeMolecular Probes, Inc.
InventorsRichard P. Haugland, Mohammad N. Malekzadeh, Yu-zhong Zhang
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Abstract
The dyes of the present invention are fluorescent substituted 3',6'-diaminoxanthenes and their reduced analogs 3',6'-diaminodihydroxanthenes, which are oxidized to the fluorescent form of the dye in situ. In their oxidized form, the dyes selectively localize within mitochondria. The dyes of the present invention include an alkylating group that is covalently attached that allows their retention in mitochondria even after cell death, fixation, and permeabilization.
Claims8
A compound of the formula ##STR13## or of the formula ##STR14## wherein a fused-ring system has ring substituents R.sup.1, R.sup.4, R.sup.5, and R.sup.8 are independently H, Cl, Br, I, (CH.sub.2).sub.n CH.sub.3, or (CH.sub.2).sub.n CO.sub.2 R.sup.13, where n is an integer from 0 to 15 and R.sup.13 is an alkyl with 1-6 carbons;
- and amino substituents R.sup.2, R.sup.3, R.sup.6, and R.sup.7 that are independently H or C.sub.1 -C.sub.6 alkyl;
- or optionally any ring substituent in combination with an adjacent amino substituent independently forms an additional fused ring such that R.sup.1 in combination with R.sup.2, R.sup.3 in combination with R.sup.4, R.sup.5 in combination with R.sup.6, and R.sup.7 in combination with R.sup.8 is (CH.sub.2).sub.3 or (CH.sub.2).sub.2 ;
- .OMEGA. is a single covalent bond or .OMEGA. is --Z--Y--where
- Z is attached to the fused ring system, and Z is a covalent bond, or Z is (CH.sub.2).sub.i where i=1-6, or Z is ##STR15## where R.sup.11 is a hydrocarbon chain with 1-6 carbons that is branched, unbranched, saturated or unsaturated;
- Y is a covalent bond or Y has the formula --OCH.sub.2 R.sup.12 --, --OR.sup.13 --, --SR.sup.12 --, --SR.sup.13 --, --NHCOCH.sub.2 R.sup.12 --, --NHCOR.sub.13 --, --CONHCH.sub.2 R.sup.12 --, --CONHR.sup.13 --, --NHSO.sub.2 R.sup.12 --, --NHSO.sup.2 R.sup.13 --, --NHCONHCH.sub.2 R.sup.12 --, --NHCONHR.sup.13 --, --NHCSNHCH.sub.2 R.sup.12 --, or --NHCSNHR.sup.13 --, where R.sup.12 is (CH.sub.2).sub.m and m=1-18, and R.sup.13 is phenylene (--C.sub.6 H.sub.4 --);
- such that Z and Y are not both covalent bonds;
- A is an alkylating group that is
- CR.sup.9 R.sup.10 X, where R.sup.9 and R.sup.10 are independently H or CH.sub.3, and X is Cl, Br, I, or --OSO.sub.2 R.sup.16, where R.sup.16 is C.sub.1 -C.sub.6 alkyl;
- C.sub.1 -C.sub.6 perfluoroalkyl;
- or R.sup.16 is phenyl, or phenyl substituted one or more times by C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 perfluoroalkyl, Cl, Br, I, NO.sub.2, or CN;
- or
- the alkylating group A is maleimidyl (--NC.sub.4 H.sub.2 O.sub.2) or haloacetamido (--NH(C.dbd.O)--CH.sub.2 ) where is Cl, Br or I;
- and
- .PSI. is a biologically compatible counterion.
Dependencies are inferred from the claim text.