Controlled release composition

Details Controlled release composition Controlled release composition

2001-02-28

2004-07-20

Kiliman, Leszek (Department: 1773)

Stock material or miscellaneous articles

Composite

Of metal

C428S458000, C428S459000, C427S299000, C427S388100, C435S006120, C536S092000

Reexamination Certificate

active

06764768

ABSTRACT:

BACKGROUND
The present invention relates to self-assembled monolayers (SAMs) of alkanethiolates.
SAMs of alkanethiolates on gold are an important class of model substrates for mechanistic studies of the interactions of proteins and cells with surfaces. They have been used in monolayers that are inert in biological fluids—in that they prevent protein adsorption and cell adhesion—and provide surfaces for patterning the positions and shapes of attached cells (Mrksich, M.; Dike, L. E.; Tien, J. Y.; Ingber, D. E.; Whitesides, G. M.
Exp. Cell Res
. 1997, 235, 305-313; and Chen, C. S.; Mrksich, M.; Huang, S.; Whitesides, G. M.; Ingber, D. E.
Science
1997, 276, 1345-1347). The attachment of ligands to these inert SAMs gives surfaces to which proteins and other receptors selectively bind. Monolayers presenting peptide ligands, for example, have been used to control the adhesion of cells (Roberts, C.; Chen, C. S.; Mrksich, M.; Martichonok, V.; Ingber, D. E.; Whitesides, G. M.
J. Am. Chem. Soc
. 1998, 120, 6548-6555; and Houseman, B. T.; Mrksich, M.
J. Org. Chem
. 1998, 120, 6548-6555) and monolayers presenting oligonucleotides have been used for probing gene expression in cells (Bamdad, C.
Biophys. J
. 1998, 75, 1997-2003).
A new challenge in biointerfacial science is to design dynamic substrates that can alter, in real-time, the display of ligands, and hence interactions of proteins and cells with the substrate (Lau, A. N. K.; Miller, L. L.
J. Am. Chem. Soc
. 1983, 105, 5271-5277; and Ding, Z.; Long, C. J.; Hayashi, Y.; Bulmus, E. V.; Joffman, A. S.; Stayton, P. S.
Bioconjugate Chem
. 1999, 10, 395-400). Previously, a dynamic SAM that could be switched from a state that is initially inert to a state that permits the Diels-Alder mediated immobilization of ligands has been demonstrated, which in turn provides a strategy to activate the selective binding of proteins to a substrate (Yousaf, M. N.; Mrksich, M.
J. Am. Chem. Soc
. 1999, 121, 4286-4287). Previous examples of substrates that can release attached cells have relied on a thermally responsive poly(N-isopropylacrylamide) film (T. Okano, N. Yamata, J. Sakai, Y. Sakurai,
Biomaterials
1995, 16, 297-303; and Y. Ito, G. Chen, Y. Guan, Y. Imanishi,
Lanmuir
1997, 13, 2756-2759).
It would be desirable to have a dynamic monolayer that can selectively release immobilized ligands. Such a monolayer could be used to regulate, in real-time, the ligand-receptor interactions between a cell and the substrate to which it is attached, and give dynamic control of the proteins presented on the surface of a monolayer. It may also be used in microsystems to regulate the release of reagents or biomolecules from a solid or gel phase.
BRIEF SUMMARY
In a first aspect, the present invention is an alkanethiol of formula (1):
HS—L—Q
1
—T—Q
2
—M—G—Z  (1),
wherein —L— is —(A
L
j
—B
L
k
—E
L
l
—D
L
)
m
—;
each A
L
, B
L
, E
L
and D
L
are individually C(R
L
A
R
L
A
′)—, —C(R
L
B
, R
L
B
′)—, —C(R
L
E
R
L
E
′)—, and —C(R
L
D
R
L
D
′)—, respectively;
each R
L
A
, R
L
B
, R
L
E
and R
L
D
are individually H, or any two of R
L
A
, R
L
B
, R
L
E
and R
L
D
together form a bond, or R
L
A
, R
L
B
, R
L
E
and R
L
D
together with the atoms to which they are bonded form a six-membered aromatic ring;
each R
L
A
′, R
L
B
′, R
L
E
′ and R
L
D
′ are individually H, or any two of R
L
A
′, R
L
B
′, R
L
E
′ and R
L
D
′ together form a bond, or R
L
A
′, R
L
B
′, R
L
E
′ and R
L
D
′ together with the atoms to which they are bonded form a six-membered aromatic ring;
each j, k and l are individually either 0 or 1;
m is 1 to 5;
—Q
1
— and —Q
2
— are each individually selected from the group consisting of
—T— is a moiety of formula (2) or formula (3)
R
1
and R
2
are each individually selected from the group consisting of H and OH;
a is 0 to 3;
b is 0 to 3;
indicates that the chirality of the carbon atom to which it is attached may be either R or S;
n is 1 to 6;
—M— is —(A
x
—B
y
—E
z
—D)
w
—,
A is —O—, —S—, —N(R
A
)— or —C(R
A
R
A
′)—;
B is —O—, —S—, —N(R
B
)— or —C(R
B
R
B
′)—;
E is —O—, —S—, —N(R
E
)— or —C(R
E
R
E
′)—;
D is —C(R
D
R
D
′)—;
each R
A
, R
B
, R
E
and R
D
is selected from the group consisting of H, alkyl, alkenyl, alkynyl, aryl and heterocyclic radical, or any two of R
A
, R
B
, R
E
and R
D
together form a bond, or any two of R
A
, R
B
, R
E
and R
D
together with the atoms to which they are bonded for a ring;
each R
A
′, R
B
′, R
E
′ and R
D
′ is selected from the group consisting of H, alkyl, alkenyl, alkynyl, aryl and heterocyclic radical, or any two of R
A
′, R
B
′, R
E
′ and R
D
′ together form a bond, or any two R
A
′, R
B
′, R
E
′ and R
D
′ together with the atoms to which they are bonded for a ring;
each x, y and z is either 0 or 1;
—G— is a moiety of formula (4)
R
3
, R
4
, and R
5
are each individually a —CH
2
— group substituted with a hydrogen or an alkyl group;
R
6
is a hydrogen, alkyl, alkenyl, alkynyl, aryl, halogen, heterocyclic radical or nitro group;
X is a bond or —(A
X
p
—B
X
q
—E
X
r
—D
X
)
s
—;
each A
X
, B
X
, E
X
and D
X
is individually C(R
X
A
R
X
A
′)—, —C(R
X
B
R
B
′)—, —C(R
X
E
R
E
′)—, or —C(R
X
D
R
X
D
′)—, respectively;
each R
X
A
, R
X
B
, R
X
E
and R
X
D
is individually H, or any two of R
X
A
, R
X
B
, R
X
E
and R
X
D
together form a bond, or R
X
A
, R
X
B
, R
X
E
and R
X
D
together with the atoms to which they are bonded form a six-membered aromatic ring;
each R
X
A
′, R
X
B
′, R
X
E
′ and R
X
D
′ is individually H, or any two of R
X
A
′, R
X
B
′, R
X
E
′ and R
X
D
′ together form a bond, or R
X
A
′, R
X
B
′, R
X
E
′ and R
X
D
′ together with the atoms to which they are bonded form a six-membered aromatic ring;
each p, q and r is individually either 0 or 1;
s is 1 to 5;
Y is —O— or —NH—;
R
7
and R
8
are both single bonds, or together with the atoms to which they are bonded from one or more fused rings, substituted or unsubstituted, optionally containing heteroatoms; and
—Z is a leaving group.
In a second aspect, the present invention is a disulfide of formula (5):
J—S—S—L—Q
1
—T—Q
2
—M—G—Z  (5),
where —L—, —Q
1
—, —Q
2
—, —T—, —M—, —G—, and —Z have the same meaning as in formula (1),
—J is selected from the group consisting of H, halogen, R, —OR, —NRR′, —C(O)R, and —C(O)OR;
R is selected from the group consisting of alkyl, alkenyl, alkynyl, aryl and heterocyclic radical; and
R′ is selected from the group consisting of H, alkyl, alkenyl, alkynyl, aryl and heterocyclic radical.
In a third aspect, the present invention is a substrate, comprising:
(i) a surface layer comprising gold, and
(ii) a plurality of moieties, on at least a portion of said surface layer,
wherein said moieties are alkanethiolate moieties of formula (8):
Surf—S—L—Q
1
—T—Q
2
—M—G—Z  (8)
where —L—, —Q
1
—, —Q
2
—, —T—, —M—, —G—, and —Z have the same meaning as in formula (1), and Surf designates where the moiety is attached to the surface.
In a fourth aspect, the present invention is a method of releasing a leaving group, comprising:
applying a reducing potential to a surface.
Definitions
“Alkyl” (or alkyl- or alk-) refers to a substituted or unsubstituted, straight, branched or cyclic hydrocarbon chain, preferably containing from 1 to 20 carbon atoms. More preferred alkyl groups are alkyl groups containing from 7 to 16 carbon atoms. Preferred cycloalkyls have from 3 to 10, preferably 3-6, carbon atoms in their ring structure. Suitable examples of unsubstituted alkyl groups include methyl, ethyl, propyl, isopropyl, cyclopropyl, butyl, iso-butyl, tert-butyl, sec-butyl, cyclobutyl, pentyl, cyclopentyl, hexyl, cyclohexyl, and the like. “Alkylaryl” and “alkylheterocyclic” groups are alkyl groups covalently bonded to an aryl or heterocyclic group, respectively.
“Alkenyl” refers to a substituted or unsubstituted,

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