aza cope rearrangement of propargyl enammonium cations catalyzed by a self-assembled...
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Aza Cope Rearrangement of Propargyl Enammonium Cations Catalyzed By a Self-Assembled “Nanozyme”
Dr. Kenneth RaymondBorn 1942; B. A. Reed College (1964); Ph. D. Northwestern University (1968); Alfred P. Sloan Research Fellow (1971-1973); Miller Research Professor (1977-1978, 1996, 2004); Guggenheim Fellow (1980-1981); Selected as one of the "Technology 100, 1981" by Technology Magazine; American Association for the Advancement of Science Fellow (1984); DOE Ernest O. Lawrence Award (1984); Lawrence Berkeley Laboratory Technology Transfer award (1988, 1991); Humboldt Research Award for Senior U.S. Scientists (1992); American Chemical Society Alfred Bader Award in Bioinorganic or Bioorganic Chemistry (1994); Erskine Fellow, University of Canterbury, New Zealand (1997); Elected to National Academy of Sciences (1997); Basolo Medal, Northwestern University (1997); Max-Planck-Institut fur Strahlenchemie "Frontiers in Biological Chemistry" Award (1997); Elected to the American Academy of Arts and Sciences (2001); Reed College Howard Vollum Award (2002); ACS Auburn Section G. M. Kosolapoff Award (2004); Izatt-Christensen Award in Macrocyclic Chemistry (2005); Joe L. Franklin Memorial Lectureship (2006); Paulo Fasella Lectureship (2006); UC Berkeley Chancellor's Professor, (2007-).
426 Pubs
126 Inorg Chem
113 JACS
21 Angew
The Cope Rearrangement
• 3,3 sigmatropic rearrangement• Aza Cope rearrangement
The Catalyst• M4L6
12- assembly• M = Ga3+ (Al3+, Fe3+); L = N,N’-bis(2,3-dihydroxybenzoyl)-
1,5-diaminonaphthalene• Racemic mixture of homochiral ΔΔΔΔ and ΛΛΛΛ
enantiomers• Anionic nature makes soluble in H2O, with hydrophobic
core• Water-labile cations (ketone-derived iminium ions,
diazonium, tropylium, phosphine-acetone adducts) are encapsulated
Enammonium synthesis
Basic Cope rearrangement of enammonium
1H NMR
• NMR in D2O
• Hi-res ES-TOF MS in H2O
Rate constantsCompound R kfree=(10-8 s-1) kencaps=(10-8 s-1) kencaps/kfree
2 H 62.4 237 4
3 Me 62.3 6200 100
4 Et 20.0 3670 184
5 n-Pr 19.5 1920 98
6 i-Pr 6.7 870 129
7 n-Bu 15.1 73 5
8 i-Bu 17.0 477 28
9 s-Bu 50.0 1150 23
R=Me has fastest encapsulation rate; zeroth order when >3 eq substrate; RLS = rearrangementrate depends on [host-bound substrate].
• Catalyzed reaction on the left; uncatalyzed on the right. ΔH‡ is more negative for the catalyzed reaction
• Entropy for catalyzed reaction is >20 J/mol more positive than for uncatalyzed
• Entropy-based rate increase
RS
hk
RTH
Tk Brate
‡‡
lnln
Michaelis-Menten in the house
Vmax = 1.2 x 10-4 mM.s-1
Km = 0.67 mM
kcat = 7.0 x 10-5 s-1
Vmax = ~1.05 x 10-4 mM.s-1
Km = >1.7 mM
kcat = ? x 10-5 s-1
The Emergence of a New Radical-Cationic Amino Acid Dynamics:
The Proton Patches ModelMatthew MacLennan
1 J. Mol. Struct. THEOCHEM0 Angew. Chem.0 JACS
Dr. Galina OrlovaRostov University, Russia, 1981-1998 (R. Minyaev)Southern Illinois University at Carbondale 1996/97 (S. Scheiner)University at Guelph 1998/2002 (J. D. Goddard)York University 2002/2004 (K.W.M. Siu, D.K. Bohme, A.C. Hopkinson)
42 Pubs10 J Phys Chem A5 JACS
Methodology
• Lowest energy conformers of neutral amino acid
• Geometry in Gaussian• Charge = +1; Multiplicity = 2 (ionization)• Run CPMD simulation to test
“Proton Scissors”12 AWFULLY
COMPLICATED STEPS
This fragmentation of C-N bond to give oxazolone cation and neutral fragment occurs at 31.3 kcal/mol. This size barrier is common with protonated species (between 30 and 40 kcal/mol). The fragmentation of any C-N or C-C bond in GGG is always preceded by proton transfer.
Fragments
+
+
Amino Acids
• Arginine
• Asparigine
• Aspartic Acid
• Threonine
• Tryptophan
Radical-Cationic Arginine (Arg+•)
Arg+•
0
2
4
6
8
10
12
0 100 200 300 400 500 600 700 800
Time (fs)
C-C
Bon
d Le
ngth
(Ang
stro
ms)
Arg+•
00.20.40.60.8
11.21.41.61.8
2
0 100 200 300 400 500 600 700 800
Time (fs)
N-H
Bon
d D
ista
nce
(Ang
stro
ms)
Radical-Cationic Asparigine (Asn+•)
Asn+•
00.20.40.60.8
11.21.41.61.8
22.2
0 100 200 300 400 500 600 700 800
Time (fs)
O-H
Bon
d Di
stan
ce (A
ngst
rom
s)
Asn+•
0
1
2
3
4
5
6
7
0 100 200 300 400 500 600 700 800
Time (fs)
C-C
Bond
Dis
tanc
e (A
ngst
rom
s)
Radical-Cationic Aspartic Acid (Asp+•)
Asp+•
0
1
2
3
4
5
6
7
0 100 200 300 400 500
Time (fs)
C-C
Bon
d D
ista
nce
(Ang
stro
ms)
Asp+•
0
1
2
3
4
5
6
0 100 200 300 400 500
Time (fs)
O-H
Bon
d Di
stan
ce (A
ngst
rom
s)
~124 fs
Radical-Cationic Threonine (Thr+•)
Radical-Cationic Tryptophan (Trp+•)
Summary• Radical-cationic amino acids do not obey the
“proton scissors” motif (Proton transfer before C-C bond cleavage); we see variety
• Arg+•, Asp+•, and Thr+• (conformer 2) show C-C bond cleavage before proton transfer
• Asn+• shows C-C bond cleavage and proton transfer occurring almost simultaneously
• Thr+•, Trp+• show C-C bond cleavage without any proton transfer
• Explanation for lack of IE potentials of amino acids
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