Prebiotic Lipidic Amphiphiles and Condensing Agents on the Early Earth

Abstract

It is still uncertain how the first minimal cellular systems evolved to the complexity required for life to begin, but it is obvious that the role of amphiphilic compounds in the origin of life is one of huge relevance. Over the last four decades a number of studies have demonstrated how amphiphilic molecules can be synthesized under plausibly prebiotic conditions. The majority of these experiments also gave evidence for the ability of so formed amphiphiles to assemble in closed membranes of vesicles that, in principle, could have compartmented first biological processes on early Earth, including the emergence of self-replicating systems. For a competitive selection of the best performing molecular replicators to become operative, some kind of bounded units capable of harboring them are indispensable. Without the competition between dynamic populations of different compartments, life itself could not be distinguished from an otherwise disparate array or network of molecular interactions. In this review, we describe experiments that demonstrate how different prebiotically-available building blocks can become precursors of phospholipids that form vesicles. We discuss the experimental conditions that resemble plausibly those of the early Earth (or elsewhere) and consider the analytical methods that were used to characterize synthetic products. Two brief sections focus on phosphorylating agents, catalysts and coupling agents with particular attention given to their geochemical context. In Section 5, we describe how condensing agents such as cyanamide and urea can promote the abiotic synthesis of phospholipids. We conclude the review by reflecting on future studies of phospholipid compartments, particularly, on evolvable chemical systems that include giant vesicles composed of different lipidic amphiphiles.

Keywords: amphiphiles; cyanamide; hydrothermal conditions; lipids; origin of life; phosphite; phosphorylation; prebiotic chemistry; urea; vesicles.

Figure 1

Possible abiotic retrosyntheses (indicated by open arrows) of long-chain alkyl phosphates (APs), single- and double-chain “incomplete” lipids (ILs) and “complete” lipids (CLs). The pathways are referring to the plausibly prebiotic reaction conditions that are listed in Table 2 and Table 3. Most of the extracted amphiphilic material was able to form liposomes or similar vesicular supramolecular structures; this is schematically represented at the top of the figure by colored vesicles bearing (symbolically) semi-permeable membranes.

Figure 2

Chemical transformations of cyanamide (1). Cyanamide was extensively used in the 60s and 70s for the condensation of amino acids into short peptides, nucleotides, and oligonucleotides. It also acts as mono-carbon donor in the synthesis of several monomers, including amino acids and nucleotides. Under simulated hydrothermal conditions, but at different pH, cyanamide dimerizes to cyanoguanidine alias dicyandiamide (2), and eventually trimerizes to give stable melamine (3), or decomposes to give still reactive dicyanamide (4). The latter has been used for the direct condensation of amino acids into peptides and for the preparation of ILs and CLs; the former was taken responsible for the production of simple peptides from Miller’s spark discharge experiments on CH₄, NH₃, and H₂O in the presence of added 1. 2 was also used in conjunction with phosphate for the phosphorylation of nucleosides and sugars at low pH through the presumed intermediacy of N-[O-(phosphatidyl)carbamoyl]guanidine (5). Direct hydrolysis of 1 yields urea (6), another useful prebiotic coupling agent for the formation of APs when present with orthophosphate (see Figure 3).

Figure 3

(a) Formation of peptide bonds using cyanamide (1) as coupling agent (adapted from [70], see also Scheme 2 in [79] and Scheme 1 in [80]); (b) Phosphorylation of long-chain alcohols (formation of APs) using urea and phosphate as condensing agent (adapted from [56]). Intermediate 9 is chemically related to intermediate 5 (cf. Figure 2).

Figure 4

Proposed model for the direct phosphorylation/phosphitylation of ILs to CLs on vesicular membranes. In the prebiotic environment ILs can be synthesized under simulated hydrothermal conditions. In the presence of prebiotically plausible co-surfactants, such molecules can assemble into supramolecular vesicular structures (blue vesicles). Once formed, the ILs present on the surface of the vesicles are phosphorylated/phosphitylated by P(III) and/or P(V) salts in the presence of a condensing agent.