Stock material or miscellaneous articles – Coated or structually defined flake – particle – cell – strand,... – Particulate matter
Reexamination Certificate
2001-01-31
2003-03-04
Moore, Margaret G. (Department: 1712)
Stock material or miscellaneous articles
Coated or structually defined flake, particle, cell, strand,...
Particulate matter
C428S402000, C428S404000, C055S524000, C096S101000, C096S108000, C096S290000
Reexamination Certificate
active
06528167
ABSTRACT:
BACKGROUND OF THE INVENTION
Packing materials for liquid chromatography (LC) are generally classified into two types: those having organic or polymeric carriers, e.g., polystyrene polymers; and those having inorganic carriers typified by silica gel. The polymeric materials are chemically stable against alkaline and acidic mobile phases; therefore, the pH range of the eluent used with polymeric chromatographic materials is wide, compared with the silica carriers. However, polymeric chromatographic materials generally result in columns having low efficiency, leading to inadequate separation performance, particularly with low molecular-weight analytes. Furthermore, polymeric chromatographic materials shrink and swell upon solvent changeover in the eluting solution.
On the other hand, silica gel-based chromatographic devices, e.g., HPLC columns, are most commonly used. The most common applications employ a silica which has been surface-derivatized with an organic functional group such as octadecyl (C
18
), octyl (C
8
), phenyl, amino, cyano group, etc. As a stationary phase for HPLC, these packing materials result in columns with high theoretical plate number/high efficiency, and do not evidence shrinking or swelling. Silica gel is characterized by the presence of silanol groups on its surface. During a typical derivatization process such as reaction with octadecyldimethylchlorosilane, at least 50% of the surface silanol groups remain unreacted.
A drawback with silica-based columns is their limited hydrolytic stability. First, the incomplete derivatization of the silica gel leaves a bare silica surface which can be readily dissolved under alkaline conditions, generally pH>8.0, leading to the subsequent collapse of the chromatographic bed. Secondly, the bonded phase can be stripped off of the surface under acidic conditions, generally pH<2.0, and eluted off the column by the mobile phase, causing loss of analyte retention, and an increase in the concentration of surface silanol groups. These problems have been attributed to free silanol group activity and hydrolytic instability of silica-based stationary phases. To address to these problem, many methods have been tried including use of ultrapure silica, carbonized silica, coating of the silica surface with polymeric materials, endcapping free silanol groups with a short-chain reagent such as trimethylchlorosilane, and the addition of suppressors such as amines to the eluent. These approaches have not proven to be completely satisfactory in practice.
Hybrid columns which combine organic and silica systems are known (XTerra™ MS C
18
(Waters Corp., Milford, Mass. USA) and offer, potentially, the benefits of both silica and organic based materials. Hybrid particles have the advantages of both silica and polymer packing materials. In particular, hybrid particles offer mechanical strength, high efficiency, ability to separate a wide range of compounds, high chemical and temperature stability with little to no peak tailing, and improved peak shape for basic compounds. However, these materials have certain limitations, also.
Many of the limitations of hybrid silica-based columns can be attributed to surface organic (i.e., methyl groups). In particular, the presence of surface organic groups lead to lower bonded phase surface concentrations after bonding with silanes, e.g., C
18
and C
8
silanes, in comparison to silica phases, presumably because the methyl groups on the surface are unreactive to bonding. Further, in C
18
bonded phases, surface organic groups may decrease the level of cross-bonding between adjacent C
18
ligands. This results in reduced low pH stability since the C
18
ligand has fewer covalent bonds to the surface of the particle. Ultimately, reduced retention times and peak compression can result from the reduced low pH stability caused by surface organic groups.
SUMMARY OF THE INVENTION
The present invention relates to improved hybrid chromatographic materials which demonstrate improved stability and separation characteristics. The chromatographic hybrid particles can be used for performing separations or for participating in chemical reactions. These particles feature a surface with a desired bonded phase, e.g., ODS or CN, and a controlled surface concentration of silicon-methyl groups. More particularly, surface silicon-methyl groups are selectively replaced with silanol groups. In so doing, the hybrid particles have substantially improved low pH stability, and improved chromatographic separation performance including reduced peak tailing.
In an embodiment, particles of the invention have an interior area and an exterior surface and are of a composition represented by:
[A]
y
[B]
x
(Formula I)
where x and y are whole number integers and A is represented by:
SiO
2
/(R
1
p
R
2
q
SiO
t
)
n
(Formula II),
and/or
SiO
2
/[R
3
(R
1
r
SiO
t
)
m
]
n
(Formula III);
where R
1
and R
2
are independently a substituted or unsubstituted C
1
to C
7
alkyl group or a substituted or unsubstituted aryl group, R
3
is a substituted or unsubstituted C
1
to C
7
alkylene, alkenylene, alkynylene, or arylene group bridging two or more silicon atoms, p and q are 0, 1, or 2, provided that p+q=1 or 2, and that when p+q=1, t=1.5, and when p+q=2, t=1; r is 0 or 1, provided that when r=0, t=1.5, and when r=1, t=1; m is an integer greater than or equal to 2; and n is a number from 0.01 to 100. B is represented by:
SiO
2
/(R
4
v
SiO
t
)
n
(Formula IV)
where R
4
may be hydroxyl, fluorine, alkoxy (e.g., methoxy), aryloxy, substituted siloxane, protein, peptide, carbohydrate, nucleic acid, and combinations thereof, and R
4
is not R
1
, R
2
, or R
3
. v is 1 or 2, provided that when v=1, t=1.5, and when v=2, t=1; and n is a number from 0.01 to 100. The interior of the particle has a composition of A, the exterior surface of the particle has a composition represented by A and B, and the exterior composition is between about 1 and about 99% of the composition of B and the remainder including A. In these particles, R
4
may be represented by:
—OSi(R
5
)
2
—R
6
(Formula V)
where R
5
may be a C
1
to C
6
straight, cyclic, or branched alkyl, aryl, or alkoxy group, a hydroxyl group, or a siloxane group, and R
6
may be a C
1
to C
36
straight, cyclic, or branched alkyl (e.g., C
18
, cyanopropyl), aryl, or alkoxy group, where the groups of R
6
are unsubstituted or substituted with one or more moieties such as halogen, cyano, amino, diol, nitro, ether, carbonyl, epoxide, sulfonyl, cation exchanger, anion exchanger, carbamate, amide, urea, peptide, protein, carbohydrate, and nucleic acid functionalities.
In another embodiment, R
6
may greater than about 2.5 &mgr;mol/m
2
, more preferably greater than about 3.0 &mgr;mol/m
2
, and still more preferably greater than about 3.5 &mgr;mol/m
2
. In a preferred embodiment, the surface concentration of R
6
is between about 2.5 and about 3.7 &mgr;mol/m
2
.
This invention further provides a method of preparation of particles for performing separations or for participating in chemical reactions, including: prepolymerizing a mixture of an organoalkoxysilane and a tetraalkoxysilane (e.g., tetramethoxysilane and tetraethoxysilane) in the presence of an acid catalyst to produce a polyalkoxysiloxane; preparing an aqueous surfactant containing suspension of the polyalkoxysiloxane, and gelling in the presence of a base catalyst so as to produce porous particles having silicon C
1
to C
7
alkyl groups, substituted or unsubstituted aryl groups, substituted or unsubstituted C
1
to C
7
alkylene, alkenylene, alkynylene, or arylene groups; modifying the pore structure of the porous particles by hydrothermal treatment; and replacing one or more surface C
1
to C
7
alkyl groups, substituted or unsubstituted aryl groups, substituted or unsubstituted C
1
to C
7
alkylene, alkenylene, alkynylene, or arylene groups of the particl
Hanley Elizabeth A.
Lahive & Cockfield LLP
Lauro Peter C.
Moore Margaret G.
Waters Investments Limited
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