Paley's watchmaker analogy and prebiotic synthetic chemistry in surfactant assemblies. Formaldehyde scavenging by pyrroles leading to porphyrins as a case study

Article abstract of DOI:10.1039/c5ob01409c

The formation of elaborate molecules is regarded as an essential first step in prebiotic chemistry, but how such transformations could spontaneously occur, particularly in dilute aqueous conditions, remains poorly understood. Here, micromolar concentrations of a 3,4-dialkylpyrrole and excess formaldehyde in aqueous micellar solution (pH 7) at 25 or 50 °C were found to give good yield (up to 40%) of the lipophilic octaalkylporphyrin. The reaction occurs despite a mean occupancy number of ～0.1 pyrrole molecules/micelle, and <1 of 10 000 micelles initially containing the requisite 4 pyrrole molecules to form the porphyrin assuming a (random) Poisson distribution. Yields of up to 13% were observed in large, unilamellar phosphatidylcholine vesicles, wherein there are ～15 000 pyrrole molecules per vesicle membrane. Double-labeling crossover experiments (of 3,4-diethylpyrrole and 3,4-dimethylpyrrole) examined by mass spectrometry revealed facile exchange processes of reactive constituents among both micelle and vesicle surfactant assemblies. Together, the exchange of pyrrolic reactants among micelles and the thermodynamic driving force for tetrapyrrole formation overcome the apparent statistical odds against reaction. The fruitful exchange, accumulation and reaction of minute quantities of reactants in aqueous-surfactant assemblies suggest a general means for formation of prebiotically valuable constituents, even when the statistical odds at the outset are overwhelmingly improbable.

Full text of DOI:10.1039/c5ob01409c

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PAPER
Paley’s watchmaker analogy and prebiotic
synthetic chemistry in surfactant assemblies.
Formaldehyde scavenging by pyrroles leading
to porphyrins as a case study†
Cite this: Org. Biomol. Chem., 2015,
13, 10025
Eric J. Alexy, Carl W. Hintz, Hubert M. Hughes, Masahiko Taniguchi and
Jonathan S. Lindsey*
The formation of elaborate molecules is regarded as an essential first step in prebiotic chemistry, but how
such transformations could spontaneously occur, particularly in dilute aqueous conditions, remains
poorly understood. Here, micromolar concentrations of a 3,4-dialkylpyrrole and excess formaldehyde in
aqueous micellar solution (pH 7) at 25 or 50 °C were found to give good yield (up to 40%) of the lipophilic
octaalkylporphyrin. The reaction occurs despite a mean occupancy number of ∼0.1 pyrrole molecules/
micelle, and <1 of 10 000 micelles initially containing the requisite 4 pyrrole molecules to form the por-
phyrin assuming a (random) Poisson distribution. Yields of up to 13% were observed in large, unilamellar
phosphatidylcholine vesicles, wherein there are ∼15 000 pyrrole molecules per vesicle membrane.
Double-labeling crossover experiments (of 3,4-diethylpyrrole and 3,4-dimethylpyrrole) examined by mass
spectrometry revealed facile exchange processes of reactive constituents among both micelle and vesicle
surfactant assemblies. Together, the exchange of pyrrolic reactants among micelles and the thermo-
dynamic driving force for tetrapyrrole formation overcome the apparent statistical odds against reaction.
The fruitful exchange, accumulation and reaction of minute quantities of reactants in aqueous-surfactant
assemblies suggest a general means for formation of prebiotically valuable constituents, even when the
statistical odds at the outset are overwhelmingly improbable.
Received 10th July 2015,
Accepted 12th August 2015
DOI: 10.1039/c5ob01409c
www.rsc.org/obc
Earth has been suggested to be <1 mM.4 Methods of concen-
tration have been proposed,5 yet experimental implementation
Introduction
Paley’s watchmaker analogy,1,2 which dates to the turn of the appears to be rare.
19th century, expresses the statistical improbability of the spon-
Our interests in chemical models for the origin of photo-
taneous origin of life – in particular, that the formation of synthetic pigments6–10 have led to examination of reactions in
valuable constituents and their accumulation to afford an surfactant media, where hydrophobic reactants and products
organized functional ensemble are not expected to occur by are expected to accumulate. Two recent reports bear on the
chance. Concerning the formation of valuable constituents, a studies reported herein. First, Cleaves described a host of fruit-
large body of work beginning with the Miller–Urey experiment ful reactions of formaldehyde, a plausible prebiotic reactant.11
in the 1950s has identified structure-directed reactions that Second, Fox and Strasdeit described the formation of numer-
yield plausible prebiotic reactants (amino acids, sugars, surfac- ous alkylpyrroles, albeit in trace quantities, by thermolysis of
tants, nucleic acid bases, etc.). Considerably less success has amino acids in aqueous solution.12 While the reaction of form-
been achieved in the formation of organized assemblies of aldehyde with a 3,4-dialkylpyrrole is a well-known path to an
diverse molecules, which is necessary to generate a functional octaalkylporphyrin (Scheme 1),13–15 the conditions in the syn-
protocell.3 Regardless, many studies in prebiotic chemistry thesis lab employ strong acids and high concentrations. meso-
concern reactions at very high concentrations, yet the concen- Tetraarylporphyrins have been prepared in aqueous-surfactant
tration of dissolved organic compounds in the ocean of early media, but again in the presence of strong acids and concen-
trations of 4 mM (ref. 16) or 10 mM.17 By contrast, our interest
was in examining octaalkylporphyrin formation under neutral
conditions with tiny (10s of μM) concentrations of the pyrrole,
Department of Chemistry, North Carolina State University, Raleigh, North Carolina
27695-8204, USA. E-mail: jlindsey@ncsu.edu
†Electronic supplementary information (ESI) available: Further experimental
more representative of what might be expected under prebiotic
conditions. Given the lipophilic nature of such porphyrins,18
information and data. See DOI: 10.1039/c5ob01409c
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of the vial were transferred to a 1 cm pathlength cuvette, and
the porphyrin yield was obtained via absorption spectroscopy
as described in the next section. Spreadsheets for sets of analo-
gous reactions are provided in Tables S1 and S2.†
Porphyrin yield determination
Porphyrin yields were determined by absorption spectroscopy
from the intensity of the Soret band with manual subtraction
of the non-porphyrin background.19 The net absorption value
was used to calculate the porphyrin concentration in the reac-
tion mixture via Beer’s law, using εSoret = 159 000 M−1 cm−1 in
all cases.15 The entire reaction mixture was either placed
directly in the cuvette for yield determination or diluted if
needed to achieve a more suitable concentration. For reactions
in micelles, such dilutions were carried out in a larger quantity
of the same aqueous buffer-micellar medium. For reactions in
vesicles, disruption of the vesicles (to avoid light-scattering)
was achieved by addition of excess SDS accompanied by brief
sonication (benchtop sonication bath). The amount of added
SDS varied across reactions – the typical procedure entailed
addition of 200 µL of 300 mM SDS solution followed by soni-
cation, with the process repeated as necessary until an opti-
cally clear solution was obtained.
Scheme 1 Formaldehyde scavenging by a 3,4-dialkylpyrrole leads to
the porphyrin.
and the fact that extant photosynthetic machinery is localized
in membranes, the reactions were carried out in aqueous-sur-
factant assemblies. Here, we report results concerning for-
mation
of
octaalkylporphyrins
from
pyrroles
and
formaldehyde, and in so doing reveal facile reactant exchange
processes among aqueous micelles and vesicles. The facile
exchange provides a path for reaction despite the initial odds,
which would appear to doom the reaction altogether.
For many porphyrin-forming reactions, an oxidant (e.g., I2,
p-chloranil, DDQ, air) is required to convert the porphyrinogen
(or other hydroporphyrins) to the porphyrin.19 Here, the por-
phyrin formed without added oxidant (indeed, treatment with
I2/ethanol gave no increase in yield), regardless if the reaction
was carried out under an inert atmosphere; hence an explicit
oxidation step was omitted. In those reactions where the yield
of porphyrin was 0%, treatment with I2/ethanol6 was per-
formed to insure that any macrocycles were not missed, but
again, in no case was porphyrin observed. The porphyrin was
further characterized by fluorescence (emission, excitation)
spectroscopy and MALDI-MS.
Experimental section
General features
Micellar experiments were conducted with 30 mM cetyltri-
methylammonium chloride (CTAC) or sodium dodecyl sulfate
(SDS) as the surfactant and 0.3 M potassium phosphate (pH 7)
buffer. Stock solutions of 3,4-diethylpyrrole (1-Et, in metha-
nol), 3,4-dimethylpyrrole (1-Me, in methanol) and formal-
dehyde (in water) were prepared and used each week. The
stock concentrations of the pyrroles varied so that only 25 µL
of a stock solution was added to a reaction vial, thereby ensur-
ing that the amount of methanol in each reaction was constant
and low. The pyrrole stocks were stored at −15 °C, and the for-
maldehyde stocks at 4 °C. All materials were obtained from
commercial sources.
Preparation of lipid vesicles
Large, unilamellar vesicles (diameter ∼106 nm) of L-α-phos-
phatidylcholine (PC) were prepared by extrusion7,20 to give a
65 mM suspension that was diluted into 0.1 M potassium
phosphate buffer (pH 7) to give the desired concentration of
vesicles for reactions (see the ESI for a full description and
Representative procedure
The following stock solutions were prepared: (1) 1-Et in metha- Fig. S1†).
nol (0.80 mM), (2) formaldehyde in deionized water (80 mM),
and (3) CTAC (50 mM) in 0.5 M potassium phosphate buffer
Double-labeling crossover experiment
(pH 7). A 3 mL reaction vial was charged with 25 µL of the Four stock solutions were prepared: (1) 4 mM 1-Et in metha-
0.80 mM 1-Et solution, 1200 µL of the 50 mM CTAC solution, nol, (2) 4 mM 1-Me in methanol, (3) 200 mM formaldehyde in
and 750 µL of deionized water. The resulting mixture was deionized water, and (4) 50 mM SDS in 0.5 M phosphate buffer
stirred for 1 min, and then treated with 25 µL of the 80 mM (pH 7). In a “pre-mixed” control experiment, a vial containing
formaldehyde solution. The total reaction volume was 2000 µL, 1500 μL of the SDS solution and 913 μL of deionized water was
with corresponding 1-Et and formaldehyde concentrations treated with 14.5 μL of each pyrrole solution, such that the
of 0.010 mM and 1.0 mM, respectively. The vial was sealed combined concentration of 1-Et and 1-Me was 0.046 mM. The
(a syringe needle pierced the cap to ensure no pressure build-up), contents of the vial were stirred for 5 min, then treated with
placed in a heating block held at 25 °C, and stirred for 24 h 58 μL of the formaldehyde stock solution. The resulting
under aerobic conditions. Any solvent loss was typically <2% of mixture was stirred at 25 °C for 24 h. For the double-labeling
the total. Upon completion of the reaction, the entire contents crossover (“post-mixed”) experiment, two separate vials
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containing 1500 μL of the SDS solution and 913 μL of deio- shown in Fig. 1. The yields were substantially higher with SDS
nized water were treated with 29 μL of only one of the pyrrole than CTAC at both temperatures. The reactions at 50 °C were
stocks, such that one vial contained 0.046 mM 1-Me only and faster than at 25 °C (t1/2 = 1 or 2.5 h versus 8 or 19 h, respect-
the other contained 0.046 mM 1-Et only. These two vials were ively), as expected; regardless, under both conditions the reac-
stirred for 5 min, and subsequently mixed 0.5 : 0.5 into a third tions were essentially complete at 24 h. The reaction with 1000
vial such that the total volume was 2442 μL. This third vial was equiv. of formaldehyde was faster than that with 100 equiv.,
treated immediately with 58 μL of the formaldehyde stock yet the ultimate yield of porphyrin was essentially the same for
solution to initiate the reaction, and the mixture was stirred at the two conditions (Fig. S6†). The reaction trajectories mirror
25 °C for 24 h. Yield determination was achieved by absorption those of many aldehyde–pyrrole condensations leading to
spectroscopy. For MALDI-MS analysis, a vial was extracted porphyrins.29,30
twice with 2 mL of diethyl ether, the ether extract was concen-
To assess the robustness of the reaction conditions, a broad
trated with a stream of argon, and the concentrate was spotted range of concentrations was examined. A suitable concen-
on the matrix 1,4-bis(5-phenyloxazol-2-yl)benzene (POPOP).
tration grid for the reaction of various ratios of 3,4-diethyl-
pyrrole (1-Et) to formaldehyde was found to encompass
0.01 mM–1.0 mM of the pyrrole and varying equivalents (1, 10,
100, or 1000) of formaldehyde (points requiring >100 mM form-
aldehyde were omitted). All reactions were carried out at 25 °C
for 24 h. The results are displayed in Fig. 2. The yields at 24 h,
while not necessarily the maximum during the overall reaction
trajectory in every case, provide a reasonable measure. The sig-
nificant yield of porphyrin despite the very low concentration
of pyrrole is a striking finding. Indeed, the highest yielding
reactions occurred with concentrations approximately 100-fold
less than that for a comparable porphyrin-forming reaction in
an organic solvent.19 It is noteworthy that the reaction at
0.046 mM 1-Et affords 15% or 35% yield of porphyrin (CTAC
or SDS micelles, respectively), which corresponds to 1.7 or
4.1 μM porphyrin. Given that the concentration of surfactant
(30 mM) affords a micelle concentration of 0.20–0.58 mM, a
yield of 35% corresponds to ∼1 porphyrin per 50–140 micelles.
Differences in reaction rates in cationic versus anionic micelles
are well known and can stem from a variety of factors,31 the
delineation of which is beyond the scope of the present paper.
Calculations concerning micelles and vesicles
The concentration of micelles is given by eqn (1),
½micellesꢀ ¼ ð½surfactantꢀ ꢁ cmcÞ=Nagg
ð1Þ
where Nagg is the surfactant aggregation number and cmc is
the critical micelle concentration.21 For SDS, the cmc is
reported to be 8 mM (but can range as low as 1 mM in the
presence of high concentrations of ions);22 Nagg ranges from
∼55–120 depending on salt concentration.23,24 For CTAC, the
cmc is reported to be 1 mM (but also can be lower); Nagg
ranges from 70–90 25 (although higher values have been
reported).26,27 Upper and lower limits of values for Nagg
(50–100) and the cmc (1–10 mM) were used to bracket the
expected range of concentration of micelles. For 30 mM surfac-
tant, the result is 0.20–0.58 mM spherical micelles. This range
is employed with the pyrrole concentration to give the mean
occupancy number, m. Note that a lower value of Nagg gives an
increase in number of micelles and hence a lower value for m.
Calculated partition coefficients
Organic-aqueous partitioning coefficients (log P values) were
calculated for various diethyl-substituted saturated species
(e.g., pyrrole, pyrrole–carbinol, dipyrromethane–carbinol, por-
phyrinogen) and unsaturated species (e.g., dipyrrin–carbinol,
porphyrin) using ChemBioDraw (version 13.0.2.3020).
Results
Reactions in micelles
The reaction of pyrrole 1-Et and formaldehyde was carried out
in an aqueous micellar solution of CTAC or SDS. Formation of
the resulting octaethylporphyrin (Et8P) could be monitored
directly without treatment by an added oxidant (formaldehyde
may serve as an in situ oxidant), thereby facilitating absorption
spectrometric yield determination. The porphyrin gave fluor-
escence spectra28 (Fig. S2–S5†) nearly identical with that of an
authentic sample in a hydrocarbon solvent, as well as charac-
teristic mass spectral data.
Fig. 1 Yield of porphyrin Et8P versus time for 0.046 mM 1-Et and 100
equiv. of formaldehyde in aqueous micelles: SDS at 25 °C (solid squares)
or 50 °C (open squares); CTAC at 25 °C (solid circles) or 50 °C (open
The timecourse was examined for reactions at selected con-
centrations in CTAC or SDS micelles. The results for 0.046 mM
pyrrole and 100 equiv. of formaldehyde at 25 or 50 °C are circles).
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Fig. 2 Yield of porphyrin Et8P over a 100-fold range of pyrrole 1-Et
concentration with 1–1000 equiv. of formaldehyde at 25 °C in aqueous
micelles (pH 7) of CTAC (red, lower numbers) or SDS (blue, upper
numbers) after 24 h. The ratio of [pyrrole]/[formaldehyde] is given at the
base of each ratio line.
Several additional experiments were carried out to explore
the role of micelles. (1) Micelles convert from spherical to
rodlike in aqueous media at very high ionic strength.32,33
While the ionic strength of the 0.3 M phosphate buffer
employed herein was far below that for such a change in mor-
phology, we carried out reactions of 1-Et at even lower ionic
strength (no phosphate buffer). Thus, the reaction of 1-Et
(0.046 mM, 24 h, 25 °C) with 100 equiv. of formaldehyde in
the presence of 50 mM SDS containing NaCl at 20 or 100 mM
gave Et8P in 43% or 37% yield, respectively. (2) When SDS or
CTAC was omitted altogether (25 °C, 24 h) from the reaction,
no porphyrin was detected. These results are consistent with
reaction occurring in small, spherical micelles.
Scheme 2 Distinct models for reactions in micelles.
To assess possible exchange processes among surfactant
assemblies, double-labeling crossover experiments were per-
formed. For this study, we first examined the reactivity of 3,4-
dimethylpyrrole (1-Me). The reaction of 1-Me at 0.046 mM and
100 equiv. of formaldehyde at 25 °C in SDS micelles gave octa-
methylporphyrin (Me8P) in 23% yield. For the crossover experi-
ment, SDS micelles were separately treated with the respective
pyrrole (1-Me versus 1-Et), then mixed (“post-mixed”), treated
with formaldehyde, and allowed to react (Scheme 2). A control
(“pre-mixed”) experiment entailed adding the two pyrroles
together to the surfactant followed by formaldehyde. After
24 h, examination of the pre-mixed reaction mixture in
upon crossover experiments in CTAC micelles, or in SDS
micelles with 20 or 100 mM concentrations of NaCl (Fig. S7–
S9†). While quantitative analysis of the mass spectral data is
not possible given uncertainty about ionization efficiencies of
the porphyrin products of exchange, the data from the double-
labeling crossover experiment qualitatively are consistent with
promiscuous if not exhaustive exchange of constituents in the
micelles on the timescale of the synthesis.
Reactions in vesicles
micelles revealed a porphyrin yield of 39%. Mass spectral ana- Reactions in vesicles were examined as a counterpoint to the
lysis of the pre-mixed reaction mixture revealed the presence studies in micelles. Whereas dilution of micelles below the
of Et8P (m/z = 534.3) and Me8P (422.2) in addition to the pro- cmc results in disassembly of the micelle, vesicles remain
ducts Et6Me2P (506.3), Et4Me4P (478.3), and Et2Me6P (450.3), intact upon dilution. Unilamellar PC vesicles (∼100 nm dia-
in agreement with calculated values for the porphyrin cation meter) in aqueous solution (pH 7) were diluted to 30, 3, 0.3
radicals. The post-mixed reaction mixture gave essentially and 0.03 mM of PC. On the assumption of ∼105 molecules of
identical yield (37%) and distribution of species upon PC per vesicle,20 the concentration of vesicles was ∼300, ∼30,
MALDI-MS analysis. The mass spectral data for the reaction in ∼3 and ∼0.3 nM. Reactions were carried out at 25 °C upon
SDS micelles are shown in Fig. 3. Similar data were obtained addition of 1-Et (0.046 mM) and 100 equiv. of formaldehyde.
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Discussion
There are numerous remarkable features of the results
reported herein, including that (1) a 3,4-dialkylpyrrole is an
exceptionally potent scavenger of formaldehyde, perhaps more
so than many of the proposed prebiotic reactants;11 (2) the
reaction proceeds smoothly at neutral pH and modest temp-
erature; (3) 8 reactant molecules combine, 8 C–C bonds form
and a 6e−/6H+ dehydrogenation occurs with overall yield of up
to 40%; (4) the reaction proceeds in the presence of cationic or
anionic surfactants; and (5) the process occurs with a very low
concentration (10–50 μM) of the pyrrole. While each of these
features is noteworthy, we focus here on the latter point – in
particular, how can the successful formation of a porphyrin at
such low concentrations of the pyrrole be understood?
The concentrating effect and rate acceleration of surfactant
assemblies on organic constituents is well known.34–36 Yet,
micelles and vesicles are fundamentally different. While each
vesicle contains ∼105 surfactant molecules and a large number
of pyrrole molecules is contained in the vesicle membrane,
each micelle contains ∼50–100 surfactant molecules. Accord-
ingly, there is insufficient pyrrole to fill all of the micelles –
indeed, most micelles are empty.
The Poisson equation (eqn (2))37 can be used to describe
the random distribution of molecular species (e.g., pyrrole) in
a surfactant assembly, and is relevant here to the reactions in
micelles. Thus, m is the mean occupancy number of pyrrole
molecules per micelle, and k takes on integer values for the
number of pyrroles per micelle (k = 0, 1, 2…).
Pðx ¼ kÞ ¼ mkeꢁm=k!
ð2Þ
The mean occupancy number varies depending on the con-
centration of micelles (0.20–0.58 mM, for surfactant concen-
trations of 30 mM and a cmc ranging from 1–10 mM) and the
concentration of pyrrole employed (0.01–1.0 mM).
Fig. 3 MALDI-MS spectra for crossover experiment in 30 mM SDS at
25 °C. Panels A, B, C, and D correspond to 1-Me only (absorption spec-
troscopic yield = 23%), pre-mix control (39%), post-mix (37%), and 1-Et
only (35%), respectively.
The corresponding Poisson distribution of pyrrole per
micelles is shown in Fig. 4 for 0.39 mM micelles (for 0.20 and
0.58 mM, see Fig. S11–13†). Porphyrin formation requires four
pyrroles to create the macrocycle, thus we are interested in the
fraction of micelles that contain 4 pyrroles. For the reaction
with 0.046 mM pyrrole and 0.39 mM micelles, the mean occu-
pancy number m = 0.12 pyrrole/micelles. The fraction of
micelles with a given value of k pyrroles then is as follows: 0.89
are empty (k = 0), 0.11 contain 1 pyrrole, 0.0063 have 2 pyr-
roles, 2.5 × 10−4 contain 3 pyrroles, and 7.4 × 10−6 contain the
requisite 4 pyrroles. In other words, only 1 of ∼130 000 micelles
contains four pyrrole molecules, yet the yield of porphyrin at
this concentration is 15 or 35% (CTAC or SDS micelles). Note
that as the concentration of micelles increases, the mean occu-
pancy number m decreases for a fixed concentration of pyrrole.
For the reasonable limit of 0.20 or 0.58 mM micelles, the
Table 1 Porphyrin formation in PC vesiclesa
[PC]
(mM)
PC/pyrrole
(1-Et)
Pyrrole/
vesicle
Yield
(%)
30
3.0
650
65
150
1500
15 000
150 000
0
7.0
13
0
0.30
0.030
6.5
0.65
a Reactions employed 0.046 mM 1-Et and 4.6 mM formaldehyde at
25 °C for 24 h.
The yields for the reactions after 24 h are given in Table 1. A number containing 4 pyrroles is 9.6 × 10−5 or 1.6 × 10−6
double-labeling crossover experiment with 1-Et and 1-Me in respectively, which corresponds to only
of 10 000 or
vesicles, analogous to that in micelles, also gave complete 630 000 micelles. Indeed, upon complete site-isolation, the
,
1
exchange (Fig. S10†).
yield would be limited to the chemistry that occurs in the
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general qualitative trend (Fig. S14†), but the calculated values
for these and related molecules exhibit profound variation
across programs,18 and hence are not reliable for quantitative
evaluation.
In summary, the results reported herein are consistent
with facile reaction of minute quantities of a 3,4-dialkylpyrrole
(10–50 μM) with formaldehyde in the presence of micelles
and vesicles. The reaction process results in accumulation of
the octaalkylporphyrin in the surfactant assembly. Statistical
issues are at the heart of origin-of-life processes. Here, the
statistical distribution of pyrrole among micelles – which
would suggest little or no reaction – is overcome by (1) an
apparent exchange process that is faster than the timescale of
reaction, and (2) the thermodynamic driving force for tetra-
pyrrole macrocycle formation. The competition and transfer
of lipid constituents among vesicles has been described pre-
viously;43 here, the constituents transferred (pyrrolic reac-
tants) are far more valuable than lipids alone. The process of
transfer and accumulation of reactants in surfactant assem-
Fig. 4 Poisson distribution of the fraction of micelles having k = 0–4
pyrroles over a 100-fold range of pyrrole concentrations (for 0.39 mM
micelles).
fraction of micelles containing four pyrroles (1/10 000 to blies may have more general occurrence. Dobson and Tuck
1/630 000 micelles depending on Nagg and thus [micelle]). This and coworkers have proposed that atmospheric aerosols could
statistical analysis would suggest that almost no porphyrin serve as prebiotic reactors, where organic constituents
should form.
accumulate in high concentrations in the outer amphiphilic
The reasonable yield of porphyrin versus the statistical dis- layer of inverted micelles.44,45 Such assemblies are proposed
tribution of pyrrole among micelles suggests the micelles as sites for chemical reaction44 and perhaps chemical differ-
undergo extensive exchange of their contents during the entiation via selective partitioning of constituents upon
course of the reaction. The exchange of solutes between aerosol fission,45 thereby constituting precursors of the first
micelles has been extensively studied.21,38–41 Three distinct cells. Reactions in inverted micelles might well complement
mechanisms include (1) exit–re-entry of the solute (i.e., those in normal micelles as reported here, together providing
exchange via water mechanism); (2) micellar collision– a means for assembly of a variety of functional entities
exchange–separation (i.e., fusion–fission); and (3) micellar that otherwise appear, like Paley’s watch, to be statistically
fission–growth. The contribution of each mechanism depends unlikely.
on the surface charge of the micelle, aqueous ionic strength,
and polarity of the solute. While discrimination of such
mechanisms for the micellar formation of porphyrins is
beyond the scope of the present paper, it warrants emphasis
Acknowledgements
that even very hydrophobic substrates such as dodecylpyrene This work was supported by a grant from the NSF Chemistry of
undergo extensive exchange in minutes–hours among SDS Life Processes Program (NSF CHE-0953010). Mass spectra were
micelles.42
obtained at the Mass Spectrometry Laboratory for Biotechno-
Alternatives to facile exchange include (1) a non-random logy at North Carolina State University. Partial funding for the
distribution of the pyrrole, or (2) reaction largely in the facility was obtained from the North Carolina Biotechnology
aqueous phase. Clustering of the solute dodecylpyrene has Center and the National Science Foundation.
been observed in SDS micelles.42 In the case of clustering, one
would assume that increased concentration of the pyrrole
would afford higher yields, yet the lower concentrations of
pyrrole generally gave higher yields. Synthesis largely outside
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