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Bob
Howell
Ph.D., Ohio
University, 1971
B.S., Berea College,
1964
Office:
Dow 263
Phone:
(989) 774 - 3582
Fax:
(989) 774 - 3883
E-mail:
howel1ba@mail.cmich.edu
Research Program and
Goals:
Release Platforms
for Organoplatinum Antitumor Agents
- Organoplatinum compounds are broad spectrum, very effective antitumor
agents. Cisplatin [cis-dichlorodiammineplatinum(II)] is currently the most widely used
cancer drug. It is often used in
combination with an organic antitumor compound or Carboplatin
[1,1-cyclobutanedicarboxyalato(diammine)platinum(II); the second platinum drug
to gain widespread commercial use]. The
potential of these drugs has been limited because of the severe side effects
which accompany their administration. Among
the most debilitating side effects induced by organoplatinum drugs are 1.)
severe kidney damage and 2.) extreme nausea (as a class the platinum compounds
are among the most effective nausea producing agents known – to the point that
some patients refuse to complete the treatment regimen).
In an attempt to mitigate the toxicity of these drugs we have, for some
time, been using water soluble polymers as platforms on which a platinum drug or
prodrug might be supported and from which it might be slowly released into the
extracellular fluid. This approach
has several major potential advantages over the traditional forced hydration
therapy currently practiced. First,
the solubility of the drug formulation may be dramatically enhanced such that
the volume of fluid required to introduce a satisfactory dose of drug is
strongly diminished [Cisplatin has a solubility of about 10 mg/L in aqueous
saline]. More importantly, if the
release rate is optimal, the drug is released into the blood stream at a level
that is beneath the toxicity threshold such that side effects may be mitigated.
Most recently we have been able to place approximately forty
(1,2-diaminocyclohexane)platinum(II) moieties on the surface of a generation 4.5
PAMAM dendrimer. This polymer-drug
conjugate displays a very good release profile for the platinum species [cis-(diaquo)(1,2-diaminocyclohexane)platinum(II)].
Vinylidene Chloride
Polymers for Barrier Plastic Packaging
- Vinylidene chloride copolymers ontaining >85% vinylidene chloride
display outstanding barrier to the transport of oxygen (to prevent food
spoilage) and other small molecules as well as flavor/aroma molecules (to
prevent flavor scalping on the supermarket shelf).
For this reason these materials occupy a place of prominence in the food
packaging industry. Unfortunately,
these resins tend to undergo degradative dehydrochlorination under process
conditions. To permit commercial
exploitation of these materials the degredation must be controlled.
We are involved in an on-going program to develop vinylidene chloride
polymers with enhanced thermal stability. A
promising approach is the synthesis of polymers containing a comonomer capable
of reacting with (and consequently removing) hydrogen chloride as it is formed
to expose functionality capable of scavaging radical species.
Poly(styrene)
Containing No Head-to-Head Units - Poly(styrene) is a large volume commodity
polymer. It is widely used in
inexpensive packaging for baked goods (cookies, muffins, rolls, pastries, etc.)
and similar items. Conventional
poly(styrene) is produced by radical techniques.
Polymerization terminination occurs by radical coupling to introduce a
head-to-head unit into the mainchain. At
elevated temperature during processing this unit may undergo homoloysis to
generate macroradicals which can extrude styrene monomer.
The presence of styrene monomer in the finished item, even at very low
level, may impart objectionable flavor/aroma to the food item contained.
This problem could be avoided by using poly(styrene) containing
head-to-head units. We have been
able to develop methods for the synthesis of such a material and to demonstrate
its superior thermal stability.
Dual Functional
Flame Retardants for Polymeric Materials
- For most applications polymeric materials must be flame retarded.
Traditionally, flame retardants have been organohalogen compounds,
particularly brominated aromatics. These
compounds are readily available, inexpensive, and very effective as flame
retardants. They function by
releasing hydrogen halide into the gas phase which traps flame propagating
radicals. Because of the release of
halogen into the atmosphere, the use of these compounds is increasingly being
opposed in many parts of the world. Compounds
which might promote solid phase (charring) flame retandance as well as gas phase
activity should permit the achievement of an adequate level of flame retardance
with much reduced levels of halogen. This
has been demonstrated for several series of compounds containing both bromine
and phosphorus or bromine, nitrogen, and phosphorus.
Several potentially very effective but environmentally friendly flame
retardants are under development.
Phospholane
Initiators for Radical Polymerization
- Phosphplane containing a strained carbon-carbon bond may be prepared from
a hindered 1,2-diol and dichloro(phyenyl)phosphine or related compound.
The compounds undergo homolysis of the carbon-carbon bond at modest
temperature to afford a diradical capable of initiating vinyl polymerization.
The polymers produced contain a phosphorus moiety in the mainchain and as
a consequence exhibit flammability much lower than the corresponding polymer
containing phosphorus. Since the
phosphorus unit is part of the polymer structure it is not lost during
processing or product manufacture as a simple additive might be.
Alkoxyamine Initiator/Mediators for
Radical Polymerization via Diels-Alder Reaction
- Nitroxyl-mediated radical polymerization offers a method for the
generation of low polydispersity styrene polymers.
Hindered dienes, e.g., 1,4-diphenyl-1,3-butadine, react with
nitrosobenzene to generate substituted 1,2-oxazines.
The carbon-oxygen bond in these compounds undergo thermolysis at modest
temperatures (70 – 100° C) to generate both a carbon radical capable of
initiating polymerization and a stable nitroxyl radical suitable for mediation
of the propagation reaction.
Green Polymeric
Materials from Renewable Sources
- Renewable raw material bases for polymers are of increasing interest both
because of environmental concerns (biodegradability) and the ever-increasing
cost of petroleum feed stocks. Succinic
acid is available from a number of plant sources.
It can be reduced to 1,4-butanediol.
Thus, both monomers (the diol and succinic acid) required for the
generation of poly(butylene succinate) are available from a single source.
The properties of this and related polymers, as both the homopolymers and
as blends with more traditional materials, are being examined.
Lignin as a Source
of Green Flame Retardants
- Lignin is a natural polymer readily available as a by-product of the wood
pulping industry. It is a highly
aromatic material containing a wealth of functionality (largely phenolic groups)
for reaction with phosphorus reagents. The
phenolic groups are also activated for electrophilic halogenation.
Thus lignin may be converted via
several conventional reactions to a material with flame retardant properties.
Such materials are being generated and evaluated as flame-retardant
additives for polymeric materials.
Selected Publications:
B.A. Howell, “Kinetics of the Thermal Dehydrochlorination
of Vinylidene Chloride Barrier Polymers,” J.
Therm. Anal.
Cal.
, 83, 53 (2006).
B.A. Howell and J.A. Ray, “Comparison of Isothermal and
Dynamic Methods for the Determination of Activation Energy by Thermogravimetry,”
J. Therm. Anal.
Cal.
, 83, 53 (2006).
B.A. Howell and H.Wu, “Thermal Degradation of
2,4,6-Tri[(bromo)xanilino]-1,3,5-triazines,”
J. Therm. Anal.
Cal.
, 83, 79 (2006).
B.A. Howell and P.B. Smith, “Thermal Degradation of
Vinylidene chloride/4-Vinylpyridine Copolymers,” J. Therm. Anal.
Cal.
, 83, 71 (2006).
B.A. Howell and J. Zhang, “Thermal Degradation of
Vinylidene Chloride/Vinyl Chloride Copolymers in the Presence of N-Substitutedmaleimides,”
J. Therm. Anal.
Cal.
, 83, 83 (2006).
B.A. Howell and C.R. Ahn, “Flame Retardants from a
Renewable By-Product of the Paper Industry,” NATAS
Notes, 37(1), 7-12 (2005)
.
D.S. Gibbs, R.A. Wessling, B.E.
Obi, P.T. DeLassus, B.A. Howell and D.E. Beyer, “Vinylidene Chloride Monomer
and Polymers”, Encyclopedia of Polymer
Science and Technology, 3rd Ed., John Wiley and Sons, Inc., New
York, NY, 2002.
B.A.
Howell, K.F. Johnston and C. Liu, “Phosphonium Bromide Salts as Potential
Flame Retardants for Polymeric Materials”, Phosphorus,
Sulfur and Silicon, 147, 123
(1999).
I.Q. Li,
B.A. Howell, P.E. Kastl, J. W. Lyons, D.M. Meunier, P.B. Smith and D.B. Priddy,
"Block Copolymer Preparation Using Sequential Normal/Living Radical
Polymerization Techniques," Macromolecules,
30, 5195 (1997).
P.B. Smith,
S.S. Cutie, D.E. Henton, C. Powell, J. Kosman, and B.A. Howell, "Allyl
Endcapped Polyethylene Oxide Crosslinkers and their Use in Superabsorbants,"
J. Polym. Sci., Polym. Chem. Ed., 35,
799 (1997).
S. G. Delassus, B.
A. Howell, C.J. Cummings, V.A. Dais, R.M. Nelson and D.B. Priddy.
“Incorporation of Benzocyclobutene in Polystyrene Allowing Postpolymerizer
Chain Extension/Branchin,.” Macromolecules,
27, 1307 (1994).
B.A. Howell and H. Liu. “Impact of
Presence of Amines on the Degradation of Vinylidene Chloride Copolymers.” J.
Vinyl Tech., 13, 187 (1991).
S. L. Warner, B.A. Howell, P.B.
Smith, V.A. Dais and D. B. Priddy. “Use of GPC-UV to Determine the Location of
Functional Groups in Styrenic Polymers.” J.
Appl. Polym. Sci., 45, 461
(1992).
B.A.
Howell, E.W. Walles, and R. Rashidianfar, "Noncovalent Complexes of
Water-Soluble Polymers and Organoplatinum Compounds as Potential Time-Release
Antitumor Agents”, Makromol. Chem.,
Macromol. Symp., 19, 329 (1988).
B.A.
Howell, E.W. Walles, R. Rashidianfar, J.R. Glass, B.J. Hutchison, and D.A.
Johnson, “Complexes of Water-Soluble Polymers and Organoplatinum Compounds as
Potential Time-Release Antitumor Formulations” in “Platinum and Other Metal
Coordination Compounds in Cancer Chemotherapy”, M. Nicolini, Ed., Martinus
Nijhoff Publishing, Boston, MA, 1988.
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